Studies
IMMUNOLOGY INFLAMMATION
1) Increase in intranuclear nuclear factor kappaB and decrease in inhibitor kappaB in mononuclear cells after a mixed meal: evidence for a proinflammatory effect. Aljada A, Mohanty P, Ghanim H, Abdo T, Tripathy D, Chaudhuri A, Dandona P. Am J Clin Nutr. 2004 Apr;79(4):682-90.Learn More
BACKGROUND:
In view of the stimulatory effect of glucose on reactive oxygen species (ROS) generation, we investigated the possibly includes concomitant proinflammatory changes.
OBJECTIVE:
The objective was to determine whether the intake of a 900-kcal mixed meal induces an increase in ROS generation by leukocytes and an inflammatory response at the cellular level.
DESIGN:
Nine normal-weight subjects were given a 900-kcal mixed meal, and 8 normal-weight subjects were given 300 ml water after an overnight fast. Blood samples were collected at 0, 1, 2, and 3 h. ROS generation by mononuclear cells and polymorphonuclear leukocytes and the expression of p47(phox) subunit were measured. Intranuclear nuclear factor kappaB (NF-kappaB) binding and the expression of inhibitor kappaBalpha (IkappaBalpha), IkappaB kinase alpha (IKKalpha), and IkappaB kinase beta (IKKbeta) were measured. Plasma concentrations of C-reactive protein (CRP) and solute intercellular adhesion molecule were also measured.
RESULTS:
ROS generation by mononuclear cells and polymorphonuclear leukocytes and p47(phox) expression increased significantly. The expression of IKKalpha and IKKbeta and DNA-binding activity of NF-kappaB increased significantly, whereas IkappaBalpha expression decreased. Plasma CRP concentrations increased. The intake of 300 mL water did not induce a change in any of the above indexes.
CONCLUSIONS:
These data show that the intake of a mixed meal results in significant inflammatory changes characterized by a decreased in IkappaBalpha and an increase in NF-kappaB binding, plasma CRP, and the expression of IKKalpha, IKKbeta, and p47(phox) subunit. These proinflammatory changes are probably relevant to the state of chronic hypertension and obesity and to its association with atherosclerosis.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/15051615
2) Mouse and human neutrophils induce anaphylaxis. Jönsson F, Mancardi DA, Kita Y, Karasuyama H, Iannascoli B, Van Rooijen N, Shimizu T, Daeron M, Bruhns P. J Clin Invest. (2011) Apr 1;121(4):1484-96.Learn More
Classically, it depends on IgE, FcεRI, mast cells, and histamine. However, anaphylaxis can also be induced by IgG antibodies, and an IgG1-induced passive type of systemic anaphylaxis has been reported to depend on basophils. In addition, it was found that neither mast cells nor basophils were required in mouse models of active systemic anaphylaxis. Therefore, we investigated what antibodies, receptors, and cells are involved in active systemic anaphylaxis in mice. We found that IgG antibodies, FcγRIIIA and FcγRIV, platelet-activating factor, neutrophils, and, to a lesser extent, basophils were involved. Neutrophil activation could be monitored in vivo during anaphylaxis. Neutrophil depletion inhibited active, and also passive, systemic anaphylaxis. Importantly, mouse and human neutrophils each restored anaphylaxis in anaphylaxis-resistant mice, demonstrating that neutrophils are sufficient to induce anaphylaxis in mice and suggesting that neutrophils can contribute to anaphylaxis in humans. Our results therefore reveal an unexpected role for IgG, IgG receptors, and neutrophils in anaphylaxis in mice. These molecules and cells could be potential new targets for the development of anaphylaxis therapeutics if the same mechanism is responsible for anaphylaxis in humans.
Article Link:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069785
3) IgG subclasses and allotypes: from structure to effector functions. GesturVidarsson, Gillian Dekkers and Theo Rispens. Frontiers in Immunology October 2014 | Volume 5 | Article 520 | 1.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25368619
4) Inhibition of complement activation by IgG4 antibodies. Van der Zee JS, van Swieten P, Aalberse RC. Clin. Exp. Immunol. (1986) May: 64 (2):415-22.Learn More
in the IgG1/IgG4 ratio of the response against phospholipase-A (PLA; a major component of bee venom) occurred. This resulted in an IgG4-dominated response after approximately 2 years of bee-keeping experience. Subject of the present study was the influence of relatively high concentrations of IgG4 antibodies on the biological activity of immune complexes. In the PLA antigen model, it was demonstrated that IgG4-containing immune complexes do not activate complement and that IgG4 antibodies effectively inhibit immune precipitation and complement activation by IgG1 antibodies. Evidence is provided that IgG4 antibodies inhibit binding of C1q to IgG1 in mixed, IgG1- and IgG4- containing complexes. It is proposed that IgG4 antibodies protect against the biological effects of the complement-fixing IgG subclasses. For this reason, determination of the total IgG response or just determination of antibody activity in the complement-fixing isotypes is insufficient in immune-complex diseases. The modulating effect of the non-complement-fixing isotypes should be taken into account to predict the biological activity of the immune complexes
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/3488859
5) Immunoglobulin G4: an odd antibody. Aalberse RC, Stapel SO, Schuurman J, Rispens T. Clin Exp Allergy, (2009) 39 (4):469-77.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/19222496
6) Independent audit of IgG food intolerance tested patient survey. Sheldon TA. British Allergy Foundation, 2000.Learn More
Abstract:
BACKGROUND:
Patients with irritable bowel syndrome (IBS) often feel they have some form of dietary intolerance and frequently try exclusion diets. Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies.
AIMS:
To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food.
PATIENTS:
A total of 150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies.
METHODS:
Primary outcome measures were change in IBS symptom severity and global rating scores. Non-colonic symptomatology, quality of life, and anxiety/depression were secondary outcomes. Intention to treat analysis was undertaken using a generalised linear model.
RESULTS:
After 12 weeks, the true diet resulted in a 10% greater reduction in symptom score than the sham diet (mean difference 39 (95% confidence intervals (CI) 5–72); p = 0.024) with this value increasing to 26% in fully compliant patients (difference 98 (95% CI 52–144); p<0.001). Global rating also significantly improved in the true diet group as a whole (p = 0.048, NNT = 9) and even more in compliant patients (p = 0.006, NNT = 2.5). All other outcomes showed trends favouring the true diet. Relaxing the diet led to a 24% greater deterioration in symptoms in those on the true diet (difference 52 (95% CI 18–88); p = 0.003).
CONCLUSION:
Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.
KEYWORDS:
irritable bowel syndrome, IgG, food sensitivity, food elimination
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774223
7) Inflammation and metabolic disorders. Hotamisligil G. S. Nature, (2006), 444, 860-867.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/17167474
8) Food Allergy: Adverse Reactions to Foods and Food Additives. 4th edition page18
Edited by Dean D. Metcalfe, Hugh A. Sampson, and Ronald A. Simon c 2008 Blackwell Publishing, ISBN: 978-1-405-15129-0.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/22278172
9) Gliadin IgG antibodies and circulating immune complexes. Eisenmann A1, Murr C,
Fuchs D, Ledochowski M.Scand J Gastroenterol. 2009; 44(2):168-71.Learn More
OBJECTIVE:
Circulating immune complexes (CICs) in blood are associated with autoimmune- diseases such as systemic lupus erythematosus, immune complex glomerulonephritis, rheumatoid arthritis and vasculitis. However, slightly increased serum concentrations of such CICs are sometimes also found in healthy individuals. The objective of the current study was to assess whether food antigens could play a role in the formation of CICs.
MATERIAL AND METHODS:
A total of 352 (265 F, 87 M), so far, healthy individuals were tested for CICs containing C1q and immunoglobulin G (IgG) as well as for gliadin IgG antibodies using the ELISA technique. Additionally, fructose and lactose malabsorption was assessed using hydrogen breath tests.
RESULTS:
In our study, 15.3% (54/352) of the patients presented with elevated CIC concentrations (above 50 microg/ml) and 6.5% (23/352) of the study population were positive for gliadin IgG antibodies (above 20 U/ml). CIC concentration levels were significantly higher in the group with elevated gliadin IgG antibodies (CIC median: 49.0 microg/ml) compared with the group with normal levels of gliadin IgG antibodies (CIC median: 30.0 microg/ml; Mann-Whitney U-test, U=1992; p
<0.001). As expected, there was no difference in CIC concentrations (Mann- Whitney U-test, U=6106; p=0.783) and gliadin IgG (Mann-Whitney U-test, U=3761; p=0.411) between patients in the fructose or lactose malabsorber groups and the subjects without malabsorption.
CONCLUSIONS:
The results of this study indicate that certain food antigens (e.g. gluten) could play a role in the formation of CICs. An association between CICs and fructose or lactose malabsorption seems to be improbable.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/18819035
IBS
11) Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Gut. 2004 Oct, 53(10):1459-64. Learn More
Patients with irritable bowel syndrome (IBS) often feel they have some form of dietary intolerance and frequently try exclusion diets. Tests attempting to predict food sensitivity in IBS have been disappointing but none has utilised IgG antibodies.
Aims:
To assess the therapeutic potential of dietary elimination based on the presence of IgG antibodies to food.
Patients:
A total of 150 outpatients with IBS were randomised to receive, for three months, either a diet excluding all foods to which they had raised IgG antibodies (enzyme linked immunosorbant assay test) or a sham diet excluding the same number of foods but not those to which they had antibodies.
Methods:
Primary outcome measures were change in IBS symptom severity and global rating scores. Non-colonic symptomatology, quality of life, and anxiety/depression were secondary outcomes. Intention to treat analysis was undertaken using a generalised linear model.
Results:
After 12 weeks, the true diet resulted in a 10% greater reduction in symptom score than the sham diet (mean difference 39 (95% confidence intervals (CI) 5–72); p = 0.024) with this value increasing to 26% in fully compliant patients (difference 98 (95% CI 52–144); p<0.001). Global rating also significantly improved in the true diet group as a whole (p = 0.048, NNT = 9) and even more in compliant patients (p = 0.006, NNT = 2.5). All other outcomes showed trends favouring the true diet. Relaxing the diet led to a 24% greater deterioration in symptoms in those on the true diet (difference 52 (95% CI 18–88); p = 0.003).
Conclusion:
Food elimination based on IgG antibodies may be effective in reducing IBS symptoms and is worthy of further biomedical research.
Keywords:
irritable bowel syndrome, IgG, food sensitivity, food elimination
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774223/
12) Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity. Mansueto P,D’Alcamo A, Seidita A1Carroccio AWorld J Gastroenterol. 2015 Jun 21;21(23):7089-109.Learn More
and a dietary approach may have a place in the routine clinical management of IBS.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/26109796
13) Treating irritable bowel syndrome with a food elimination diet followed by food challenge and probiotics. Drisko J., Bischoff B., Hall M., McCullum. J of the Am college of Nutrition 2006. Vol25 (6) 514-522.Learn More
In Irritable Bowel Syndrome, the gut-associated immune system may be up- regulated resulting in immune complex production, low-grade inflammation, loss of Class I bacteria, and translocation of inflammatory mediators and macromolecules outside of the GI lumen. Since food intolerance may be one of the reasons for this upregulation, our goal was to investigate the role of food intolerance in IBS patients.
METHODS:
In this open label pilot study, we enrolled 20 patients with IBS by Rome II criteria (15 women, ages 24-81) who had failed standard medical therapies in a tertiary care GI clinic. Baseline serum IgE and IgG food and mold panels, and comprehensive stool analysis (CSA) were performed. Breath-hydrogen testing and IBS Quality-of-Life (QOL) questionnaires were obtained. Patients underwent food elimination diets based on the results of food and mold panels followed by controlled food challenge. Probiotics were also introduced. Repeat testing was performed at 6-months. We followed up with this cohort at 1 year after trial completion to assess the reported intervention and for placebo effect.
RESULTS:
Baseline abnormalities were identified on serum IgG food and mold panels in 100% of the study subjects with significant improvement after food elimination and rotation diet (p < 0.05). Significant improvements were seen in stool frequency (p < 0.05), pain (p < 0.05), and IBS-QOL scores (p < 0.0001).
Imbalances of beneficial flora and dysbiotic flora were identified in 100% of subjects by CSA. There was a trend to improvement of beneficial flora after treatment but no change in dysbiotic flora. The 1-year follow up demonstrated significant continued adherence to the food rotation diet (4.00 +/- 1.45), minimal symptomatic problems with IBS (4.00 +/- 1.17), and perception of control over IBS (4.15 +/- 1.23). The continued use of probiotics was considered less helpful (3.40
+/- 1.60).
CONCLUSION:
These data demonstrate that identifying and appropriately addressing food sensitivity in IBS patients not previously responding to standard therapy results in a sustained clinical response and impacts on overall well being and quality of life in this challenging entity.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/17229899
14) Milk protein IgG and igA : the association with milk-induced gastrointestinal symptoms in adults. Anthoni S, Savilahti E, Rautelin H, Kolho KL World J. (2009) Gastroenterol. Oct 21 ; 15 (39) 4915-8.Learn More
To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults.
METHODS:
Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland. Subjects were randomly selected from a total of 1900 adults undergoing laboratory investigations in primary care. All 400 participants had completed a questionnaire on abdominal symptoms and dairy consumption while waiting for the laboratory visit. The questionnaire covered the nature and frequency of gastrointestinal problems, the provoking food items, family history and allergies. Twelve serum samples were disqualified due to insufficient amount of sera. The levels of specific milk protein IgG and IgA were measured by using the ELISA technique. The association of the milk protein-specific antibody level was studied in relation to the milk-related gastrointestinal symptoms and dairy consumption.
RESULTS:
Subjects drinking milk (n = 265) had higher levels of milk protein IgG in their sera than non-milk drinkers (n = 123, P < 0.001). Subjects with gastrointestinal problems related to milk drinking (n = 119) consumed less milk but had higher milk protein IgG levels than those with no milk-related gastrointestinal symptoms (n = 198, P = 0.02). Among the symptomatic subjects, those reporting dyspeptic symptoms had lower milk protein IgG levels than non-dyspeptics (P < 0.05).
However, dyspepsia was not associated with milk drinking (P = 0.5). The association of high milk protein IgG levels with constipation was close to the level of statistical significance. Diarrhea had no association with milk protein IgG level (P = 0.5). With regard to minor symptoms, flatulence and bloating (P = 0.8), were not associated with milk protein IgG level. Milk protein IgA levels did not show any association with milk drinking or abdominal symptoms. The levels of milk protein IgA and IgG declined as the age of the subjects increased (P < 0.004).
CONCLUSION:
Milk protein IgG but not milk IgA seems to be associated with self-reported milk- induced gastrointestinal symptoms
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/19842221
15) Serological Investigation of Food Specific Immunoglobulin G Antibodies in Patients with
Inflammatory Bowel Diseases. Chenwen Cai, Jun Shen, Di Zhao, Yuqi Qiao, Antao Xu, Shuang Jin, Zhihua Ran, and Qing Zheng*PLoS One. 2014 Nov 13;9(11).Learn More
Dietary factors have been indicated to influence the pathogenesis and nature course of inflammatory bowel diseases (IBD) with their wide variances. The aim of the study was to assess the prevalence and clinical significance of 14 serum food specific immunoglobulin G (sIgG) antibodies in patients with IBD.
Go to: Methods
This retrospective study comprised a total of 112 patients with IBD, including 79 with Crohn’s disease (CD) and 33 with ulcerative colitis (UC). Medical records, clinical data and laboratory results were collected for analysis. Serum IgG antibodies against 14 unique food allergens were detected by semi-quantitative enzyme linked immunosorbent assay (ELISA).
Go to: Results
Food sIgG antibodies were detected in 75.9% (60/79) of CD patients, 63.6% (21/33) of UC patients and 33.1% (88/266) of healthy controls (HC). IBD patients showed the significantly higher antibodies prevalence than healthy controls (CD vs. HC, P = 0.000; UC vs. HC, P = 0.001). However no marked difference was observed between CD and UC groups (P = 0.184). More subjects were found with sensitivity to multiple antigens (≥3) in IBD than in HC group (33.9% vs.0.8%, P = 0.000). Egg was the most prevalent food allergen. There was a remarkable difference in the levels of general serum IgM (P = 0.045) and IgG (P = 0.041) between patients with positive and negative sIgG antibodies. Patients with multiple positive allergens (≥3) were especially found with significant higher total IgG levels compared with sIgG-negative patients (P = 0.003). Age was suggested as a protective factor against the occurrence of sIgG antibodies (P = 0.002).
Go to: Conclusions
The study demonstrates a high prevalence of serum IgG antibodies to specific food allergens in patients with IBD. sIgG antibodies may potentially indicate disease status in clinical and be utilized to guide diets for patients.
Article Link:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230978/
16) The value of eliminating foods according to food-specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhea. Hong Guo, Tao Jiang, Jinliang Wang, Yongchao Chang, Hai Guo, Weihong Zhang. J.Int.Med.Res.2012; 40 (1):204-10.Learn More
This study investigated the role of food intolerance in irritable bowel syndrome with diarrhoea (D-IBS).
METHODS:
Specific immunoglobulin G (IgG) antibodies against 14 common food antigens in the serum were measured in 77 patients with D-IBS and 26 healthy controls. Food-specific IgG antibodies were identified in 39 (50.65%) patients with D-IBS patients compared with four (15.38%) controls. For 12 weeks following the serological testing, 35 patients with D-IBS and food intolerance consumed diets that excluded the identified food. Changes in the main symptoms of D-IBS were evaluated before treatment and regularly during treatment in these patients.
RESULTS:
After 4 weeks’ dietary therapy, most symptoms of D-IBS had improved. By 12 weeks, all symptom scores had decreased significantly compared with the baseline scores.
CONCLUSIONS:
The 12-week specific-food exclusion diets resulted in significant improvements in abdominal pain (bloating level and frequency), diarrhoea frequency, abdominal distension, stool shape, general feelings of distress and total symptom score compared with baseline in patients with D-IBS.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/22429360
17) Alterations of food antigen-specific serum immunoglobulins G and E antibodies in patients with irritable bowel syndrome and functional dyspepsia. Zuo X. L., Li Y. Q., Li W. J., Guo Y. T., Lu X. F., Li J. M. and P. V. Desmond Clinical and Experimental Allergy 2007, 37, 823–830.Learn More
Post-prandial worsening of symptoms as well as adverse reactions to one or more foods are common in the patients with functional gastrointestinal diseases, such as irritable bowel syndrome (IBS) and functional dyspepsia (FD). However, the role played by true food allergy in the pathogenesis of these diseases is still controversial and there are no well-established tests to identify food allergy in this condition.
OBJECTIVE:
To investigate serum food antigen-specific IgG, IgE antibody and total IgE antibody titres in controls and patients with IBS and FD, and to correlate symptoms with the food antigen-specific IgG titres in IBS and FD patients.
METHODS:
Thirty-seven IBS patients, 28 FD patients and 20 healthy controls participated in this study. Serum IgG and IgE antibody titres to 14 common foods including beef, chicken, codfish, corn, crab, eggs, mushroom, milk, pork, rice, shrimp, soybean, tomatoes and wheat were analysed by ELISA. Serum total IgE titres were also measured. Last, symptomatology was assessed in the study. Results IBS patients had significantly higher titres of IgG antibody to crab (P=0.000), egg (P=0.000), shrimp (P=0.000), soybean (P=0.017) and wheat (P=0.004) than controls. FD patients had significantly higher titres of IgG antibody to egg (P=0.000) and soybean (P=0.017) than controls. The percentage of individuals with detectable positive food antigen-specific IgE antibodies of the three groups did not show any significant differences (P=0.971). There were no significant differences between IBS patients, FD patients and controls in the serum total IgE antibody titres (P=0.978). Lastly, no significant correlation was seen between symptom severity and serum food antigen-specific IgG antibody titres both in IBS and FD patients.
CONCLUSION:
Serum IgG antibody titres to some common foods increased in IBS and FD patients compared to controls. But there is no significant correlation between symptom severity and elevated serum food antigen-specific IgG antibodies in these patients.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/17517095
18) Immune Activation in patients with irritable bowel syndrome. Liebregts T, Adam B, Bredack C, Röth A, Heinzel S, Lester S, Downie-Doyle S, Smith E, Drew P, Talley NJ, Holtmann G. Gastroenterology. 2007 Mar;132(3):913-20. Epub 2007 Jan 26.Learn More
BACKGROUND AND AIMS:
We set out to test the hypothesis that irritable bowel syndrome (IBS) is characterized by an augmented cellular immune response with enhanced production of proinflammatory cytokines. We further aimed to explore whether symptoms and psychiatric comorbidity in IBS are linked to the release of proinflammatory cytokines.
METHODS:
We characterized basal and Escherichia coli lipopolysaccharide (LPS)-induced cytokine production in peripheral blood mononuclear cells (PBMCs) from 55 IBS patients (18 mixed-, 17 constipation-, 20 diarrhea-predominant) and 36 healthy controls (HCs). PBMCs were isolated by density gradient centrifugation and cultured for 24 hours with or without (1 ng/mL) LPS. Cytokine production (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1beta, and IL-6) was measured by enzyme-linked immunosorbent assay. Abdominal symptoms and psychiatric comorbidities were assessed by using the validated Bowel Disease Questionnaire and the Hospital Anxiety and Depression Scale.
RESULTS:
IBS patients showed significantly (P < .017) higher baseline TNF-alpha, IL-1beta, IL-6, and LPS-induced IL-6 levels compared with HCs. Analyzing IBS subgroups, all cytokine levels were significantly (P < .05) higher in diarrhea-predominant IBS (D-IBS) patients, whereas constipation-predominant IBS patients showed increased LPS-induced IL-1beta levels compared with HCs. Baseline TNF-alpha and LPS-induced TNF-alpha and IL-6 levels were significantly higher in patients reporting more than 3 bowel movements per day, urgency, watery stools, and pain associated with diarrhea compared with patients without these symptoms (all P < .05). LPS-induced TNF-alpha production was associated significantly (r = 0.59, P < .001) with anxiety in patients with IBS.
CONCLUSIONS:
Patients with D-IBS display enhanced proinflammatory cytokine release, and this may be associated with symptoms and anxiety.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/17383420
19) Food allergy in irritable bowel syndrome: new facts and old fallacies. Isolauri E., Rautava S., Kalliomaki M.. Gut 2004; 53 (10):1391-3.Learn More
The notion of food allergy in irritable bowel syndrome (IBS) is not new. However, recent evidence suggests significant reduction in IBS symptom severity in patients on elimination diets, provided that dietary elimination is based on foods
against which the individual had raised IgG antibodies. These findings should encourage studies dissecting the mechanisms responsible for IgG production against dietary antigens and their putative role in IBS
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1774228/
MIGRAINE
20) Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, crossover trial. Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C and Baykan B. (2010) Cephalgia 1-9. Learn More
It is well-known that specific foods trigger migraine attacks in some patients. We aimed to investigate the effect of diet restriction, based on IgG antibodies against food antigens on the course of migraine attacks in this randomised, double blind, cross-over, headache-diary based trial on 30 patients diagnosed with migraine without aura.
METHODS:
Following a 6-week baseline, IgG antibodies against 266 food antigens were detected by ELISA. Then, the patients were randomised to a 6-week diet either excluding or including specific foods with raised IgG antibodies, individually.
Following a 2-week diet-free interval after the first diet period, the same patients were given the opposite 6-week diet (provocation diet following elimination diet or vice versa). Patients and their physicians were blinded to IgG test results and the type of diet (provocation or elimination). Primary parameters were number of headache days and migraine attack count. Of 30 patients, 28 were female and 2 were male, aged 19-52 years (mean, 35 +/- 10 years).
RESULTS:
The average count of reactions with abnormally high titre was 24 +/- 11 against 266 foods. Compared to baseline, there was a statistically significant reduction in the number of headache days (from 10.5 +/- 4.4 to 7.5 +/- 3.7; P < 0.001) and number of migraine attacks (from 9.0 +/- 4.4 to 6.2 +/- 3.8; P < 0.001) in the elimination diet period.
CONCLUSION:
This is the first randomised, cross-over study in migraineurs, showing that diet restriction based on IgG antibodies is an effective strategy in reducing the frequency of migraine attacks.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/20647174
21) IgG-mediated allergy: a new mechanism for migraine attacks? Pascual J, Oterino A. Cephalalgia. 2010 Jul;30(7):777-9. doi: 10.1177/0333102410364856. Epub 2010 Mar 26.Learn More
Despite recent advances offered by modern neuroimaging and genetic techniques, the pathophysiology of migraine has not been fully clarified. As pointed out by Selby and Lance 50 years ago, a relevant proportion of patients report that their migraine attacks are usually precipitated by dietary items (1). In a survey analysing the prevalence of dietary migraine in 500 new migraine patients, Peatfield et al. found in 1984 that 19.2% of migraine patients reported sensitivity to cheese, 18.2% to chocolate ad 11.1% to citrus fruit (2). The same year, Monro et al. published a paper in the Lancet with the categorical title ‘Migraine Is a Food- Allergic Disease’, describing the treatment of just nine patients with severe refractory migraine with either sodium cromoglycate or placebo after the patients ate foods previously identified as provocants (3). Sodium cromoglycate exerted a protective effect, which made the authors conclude that a food-allergy reaction is the cause of migraine, at least in this group of patients with dietary precipitants.
Definite proof that this is a reproducible fact, however, has proved elusive. In other studies objective evidence of hypersensitivity was found in very few cases, and those reporting a reduction in migraine during formal diets not only include a low number of patients, but mostly make no serious attempt to conceal the dietary strategy from the patients, pay insufficient attention to placebo effect and include an incredible prevalence of atopic diseases in migraine patients.
One of the obstacles to acceptance of the dietary hypothesis is the lack of a clear scientific explanation of the mechanisms implicated in the development of migraine attacks supposedly precipitated by food. The first obvious proposed mechanism was an allergy mediated by IgE antibodies. Theoretically, the interaction of a food constituent with a specific IgE antibody would produce a response by activation of complement or degranulation of mast cells. Several independent studies have failed to find elevated IgE levels or complement activation during migraine attacks, even in patients with a history of food- precipitated headaches (4,5).
These results, together with the finding that diet-sensitive patients are usually sensitive to several and different foods, led to the next proposal for a common pathogenic mechanism: antigenic similarities between these disparate foods seemed less likely than sharing a common chemical constituent (2). Investigators tried to confirm the so-called ‘amine hypothesis’ first by clinical challenge tests with substances like tyramine or β-phenylethylamine. As elegantly reviewed by Peatfield (5), the results of these studies can be interpreted as inconsistent. The next step was to investigate the amines’ metabolic routes. Could the elimination pathways of such amines be deficient in dietary migraine patients? There are two major breakdown pathways for these substances in humans: oxidation by monoamine oxidase (MAO) to parahydroxyphenylacetic acid and sulphation by phenosulphotransferase to water-soluble conjugates. MAO, a mitochondrial enzyme, exists in two forms in humans, with different substrate specificities. MAO A predominates in gut mucosa and liver and preferentially inactivates catecholamines and serotonin. The human platelet contains only MAO B, which metabolises phenylethylamine, benzylamine and methylhistamine. Tyramine and dopamine are substrates for both forms (6). The easy availability of platelets led to MAO B being the only form to be studied in migraine patients. Most studies have found a low platelet MAO B activity but only during migraine attacks, both in dietary and non-dietary patients (5). The significance of these findings remains uncertain. The sulphation route has also been explored in migraine patients. A reduced urinary output of sulphated tyramine metabolites after an oral tyramine load in subjects with food-sensitive migraine has been reported.
Phenolsulphotransferase, the enzyme responsible for sulphate conjugation, has been found to exist in two forms: the phenosulphotransferase M, which sulphates the amines, including tyramine, dopamine and catecholamines, and the phenosulphotransferase P, for which no endogenous substrate has been identified (7). In studies of these two enzymes in migraine patients, only in the case of P type was this deficiency statistically significant, which would hypothetically implicate an unidentified substrate in the pathophysiology of dietary migraine (8). Finally, still within the frame of the ‘amine hypothesis’, the possibility that dietary patients could absorb more of the substances due to a deficiency or a change in sensitivity of one or more intestinal-wall enzymes has also been tested (9). Again, results have not consistently confirmed this possibility.
With all these negative results, there has been almost no interest in studying, clinically or pathophysiologically, the relationship between migraine and diet in the last two decades. As just one significant example, both the aminergic hypothesis and IgE-mediated allergy hypothesis have totally disappeared as potential
explanations for the pathophysiology of migraine attacks in the last edition of The Headaches (10), even though we do continue to see many patients who experience migraine attacks when they eat certain foods or whose migraine improves on some diets (11). In this issue of Cephalalgia, Alpay and co-workers report the results of an interesting randomised, double-blind, cross-over, headache diary–based trial with 30 patients having migraine without aura (12).
Following a six-week baseline, IgG antibodies against 266 food antigens were determined. Then the investigators randomised the patients to a six-week individualised diet either including or excluding specific foods associated with raised IgG antibodies. Following a two-week diet-free interval after the first period, the same patients were given the opposite diet. Both patients and physicians were blind to the type of diet and IgG tests. Interestingly, most patients seemed to be IgG-positive for several foods and in more than half of these cases titres were graded at least as moderate. Compared to baseline, there was a statistically significant reduction both in the number of headache days and in the number of migraine attacks in the elimination diet period. The results of this Turkish trial are in line with those of a recent Mexican study in which IgG antibodies against 108 food allergens were measured in 56 migraine patients and 56 controls without migraine. IgG antibodies were statistically more frequent in the migraine patients, who then improved on an elimination diet without the need of medication (13).
Even taking into account the limitations of the Turkish trial—the rather low number of patients, relatively short follow-up, potential carry-over effect of a cross-over design, that the positive effects of the diet could be due to non- immunological mechanisms, the specificity and sensitivity of the enzyme-linked immunosorbent assay (ELISA) test and the fact that, due to the short duration of the trial, the authors were unable to correlate the clinical response with a decrease in the level of IgG antibodies—it is true that they offer a rather convincing explanation for dietary migraine, which should be tested in future larger and longer trials.
The interest in a role for IgG antibodies in food allergy has been recently driven by the findings in irritable bowel syndrome (IBS) and functional dyspepsia.
Concurring with migraine results, the levels of IgG, and not IgE, antibodies have been shown to be increased in IBS patients and recent studies have found a significant improvement in IBS on elimination diets (14–16). Interestingly, many of the clinical characteristics of IBS are conceptually similar to those of migraine, and subjects with IBS are at higher risk than controls to suffer from migraine (17). One further proof of a role of IgG antibodies against food antigens in the development of migraine attacks is the known association between migraine and celiac disease and the improvements of celiac sufferers’ migraine after changing to a gluten-free diet (18).
The mechanisms of IgG-mediated food allergy have not been fully elucidated and remain speculative. It has been proposed that food-allergy antigens transported by way of mast cells activate T helper and B lymphocytes, increasing the production of IgG antibodies and cytokines (19). Then the increased IgG antibodies and cytokines would lead to an inflammation response, which, as pointed out by Alpay and co-workers (11), seems to play an important role in the pathophysiology of migraine attacks. Supporting this hypothesis, a recent study has shown that anti-food IgG antibodies in obese juveniles are associated with systemic inflammation (20). These data are interesting, as obesity seems to be a risk factor in the development of chronic migraine (21). Alternatively, however, elevated IgG antibodies to food could be secondary to ‘inflammation’ and therefore be more of an epiphenomenon rather than a true delayed allergic reaction. In any case, Alpay and co-workers’ results, if fully confirmed in future trials, may be important not only in terms of their obvious consequences for the management of our migraine patients, but also conceptually, as the clarification of the mechanisms through which IgG antibodies are able to lead to development of migraine attacks would improve the knowledge of migraine pathophysiology. But consequences of these findings could be even more extensive. For instance, the dramatic differences in diet between the Occidental countries, where migraine prevalence is high and almost identical, and African or Asiatic countries, where migraine prevalence is clearly lower, could theoretically explain, at least in part, these epidemiological findings.
Article Link: http://journals.sagepub.com/doi/10.1177/0333102410364856
22) Randomised controlled trial of food elimination diet based on IgG antibodies for the prevention of migraine like headaches. Natasha Mitchell et al, Nutrition Journal 2011.Learn More
Research suggests that food intolerance may be a precipitating factor for migraine like headaches.
AIM:
To evaluate the effectiveness of the ELISA (Enzyme Linked Immuno-Sorbent Assay) Test and subsequent dietary elimination advice for the prevention of migraine like headaches.
DESIGN:
Randomised controlled trial.
SETTING:
Community based volunteers in the UK.
PARTICIPANTS:
Volunteers who met the inclusion criteria for migraine like headaches and had one or more food intolerance were included in the study. Participants received either a true diet (n = 84) or a sham diet (n = 83) sheet. Participants were advised to remove the intolerant foods from their diet for 12 weeks.
MAIN OUTCOME MEASURES:
Number of headache days over a 12 week period (item A MIDAS questionnaire).
Other measures includes the total MIDAS score and total HIT-6 score.
RESULTS:
The results indicated a small decrease in the number of migraine like headaches over 12 weeks, although this difference was not statistically significant (IRR 1.15 95% CI 0.94 to 1.41, p = 0.18). At the 4 week assessment, use of the ELISA test with subsequent diet elimination advice significantly reduced the number of migraine like headaches (IRR 1.23 95%CI 1.01 to 1.50, p = 0.04). The disability and impact on daily life of migraines were not significantly different between the true and sham diet groups.
CONCLUSIONS:
Use of the ELISA test with subsequent diet elimination advice did not reduce the disability or impact on daily life of migraine like headaches or the number of migraine like headaches at 12 weeks but it did significantly reduce the number of migraine like headaches at 4 weeks.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/21835022
23) A prospective Audit of food intolerance among migraine patients in primary care clinical practice. Trevor Rees,David Watson, Susan Lipscombe, Helen Speight, Peter Cousins, Geoffrey Hardman, Andrew Dowson. (2005) Headache, Vol 2 No.1 11-14.
24) Food allergy mediated by IgG antibodies associated with migraine in adults. Arroyave Hernandez CM,Echevarria Pinto M, Hernandez Montiel HL. Rev Alerg Mex (2007);54: 162–168. Learn More
Migraine occurs with a high prevalence of 18 per cent. Management requires a tailored regimen of pharmacological and other measures based on individual clinical history. In some patients, allergen-specific IgG has been suspected to be involved in their mechanism, however, serological methods to investigate such possibility, are seldomly used.
OBJECTIVE:
The aim of this study was to investigate allergen-specific IgG in serum of patients with migraine refractory to traditional treatment.
MATERIAL AND METHODS:
Serum antibodies to specific 108 food allergens were measured by enzyme immunoassay from 56 patients with migraine and a control group without migraine.
RESULTS:
In addition to statistical significant differences in the number of positives for IgG food allergens between patients with migraine and a controlled group, elimination diets successfully control the migraine without the need of medications.
CONCLUSION:
According to the results obtained, serum IgG antibodies to common food should be investigated in patients with migraine.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/18693538
AUTOIMMUNITY
26) Molecular mimicry as a mechanism for food immune reactivities and autoimmunity. Vojdani A .Altern Ther Health Med. 2015;21 Suppl 1:34-45.Learn More
Between 7% and 10% of the world’s population suffers from some form of autoimmune disease. Each patient’s antibodies, both immunoglobulin A (IgA) + immunoglobulin M (IgM) in the saliva and immunoglobulin G (IgG) and IgA in the blood must be examined to give a complete picture of food immune reactivity. A host of health problems and autoimmune disorders have increasingly become associated with some of the most commonly consumed foods in the world, such as wheat and milk. Many of these problems can be traced to molecular mimicry.
The peptide sequences of foods such as milk and wheat are similar to those of human molecules, such as myelin oligodendrocyte glycoprotein, human islet cell tissue, and human aquaporin 4 (AQP4). This similarity can result in cross- reactivity that leads to food autoimmunity and even autoimmune disorders, such as multiple sclerosis (MS), celiac disease (CD), and neuromyelitis optica. Further research is needed to determine what other foods have dangerous sequence similarities to human tissues and what methods are available to test for the autoantibodies resulting from these molecular, mimicry-induced misfires of the immune system. The identification and removal of corresponding food triggers can then be used as the basis of therapy
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25599184
27) Cross-Reaction between Gliadin and Different Food and Tissue Antigens. Aristo Vojdani1,2*, Igal Tarash1 Food and Nutrition Sciences, 2013, 4, 20-32. Learn More
BACKGROUND:
While searching for antigliadin and anticasein antibodies in sera from coeliac patients we investigated more than 20 persons suffering from this enteropathy. In some of sera, we registered antibodies against gliadin and in parallel the appearance of anticasein antibodies. A high percentage of glutamic acid has been proven by amino acid analysis in both these proteins. Therefore we try to demonstrate the existence of cross-reactivity between them in sera from coeliac patients.
METHODS:
We analyzed sera from 5 adult patients by using Western blot (SDS-PAGE and immunoblot assay). All of them had previously proven serum antibodies against casein and gliadin. In the procedure, antigliadin-antibodies were removed from sera by adsorption with gliadin. Adsorbed antibodies were then eluted from the adsorbent.
RESULTS:
Adsorbed samples retained anticasein activity. Eluates had a strong reactivity to gliadin but not to casein.
CONCLUSION:
No cross-reactivity restricted to any of the immunoglobulin isotypes (IgG, IgM, IgA) had been proven between these two proteins. Before the final conclusion, we believe the study has to be completed by using partly of totally disassembled proteins by intestinal enzymes. It might be that enzymatic digestion could open some epitopes shared by both these proteins.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/9784660
28) Anti-Saccharomyces cerevisiae autoantibodies in autoimmune diseases: from bread baking to autoimmunity. Rinaldi M1, Perricone R, Blank M, Perricone C, Shoenfeld Y.Clin Rev Allergy Immunol.2013 Oct;45(2):152-61. Learn More
Saccharomyces are required for nutrition, proper development of Peyer’s aggregated lymphoid tissue, and tissue healing. However, even the commensal nonclassically pathogenic microbiota can trigger autoimmunity when fine regulation of immune tolerance does not work properly. For our purposes, the protein database of the National Center for Biotechnology Information (NCBI) was consulted, comparing Saccharomyces mannan to several molecules with a pathogenetic role in autoimmune diseases. Thanks to the NCBI bioinformation technology tool, several overlaps in molecular structures (50-100 %) were identified when yeast mannan, and the most common autoantigens were compared. The autoantigen U2 snRNP B″ was found to conserve a superfamily protein domain that shares 83 % of the S. cerevisiae mannan sequence.
Furthermore, ASCAs may be present years before the diagnosis of some associated autoimmune diseases as they were retrospectively found in the preserved blood samples of soldiers who became affected by Crohn’s disease years later. Our results strongly suggest that ASCAs’ role in clinical practice should be better addressed in order to evaluate their predictive or prognostic relevance.
Article link: https://www.ncbi.nlm.nih.gov/pubmed/23292495
29) Gastrointestinal disease in Sjogren’s syndrome: related to food hypersensitivities. Kim-Lee C, Suresh L, Ambrus JL Jr.Springerplus. 2015 Dec 12;4:766. Learn More
Patients with Sjogren’s syndrome (SS) frequently have irritable bowel like symptoms (IBS). Some have celiac sprue. The current studies were designed to examine the presence of food hypersensitivities in a population of patients with SS and IBS. Ten patients were selected from the autoimmune disease clinics at SUNY at Buffalo who had SS and IBS symptoms. Food hypersensitivities were determined by specific IgG ImmunoCAP(®) assays. Symptoms of abdominal pain, bloating, diarrhea and joint pain were eliminated with dietary restriction of foods to which hypersensitivity was demonstrated. Symptoms recurred with re- institution of offending foods. Resolution of fatigue required elimination of offending foods as well as treatment of underlying metabolic disorders. The presence of IBS in patients with SS should lead to investigation of food hypersensitivities as possible culprits.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/26688780
30) Lectins, agglutinins, and their roles in autoimmune reactivities.. Vojdani A.Altern Ther Health Med. 2015;21 Suppl 1:46-51. Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25599185
31) The gut–joint axis: cross reactive food antibodies inheumatoid arthritis. M Hvatum†,
L Kanerud, R Hällgren, and P Brandtzaeg, Gut. 2006 Sep; 55(9): 1240–1247. Learn More
Patients with rheumatoid arthritis (RA) often feel there is an association between food intake and rheumatoid disease severity. To investigate a putative immunological link between gut immunity and RA, food antibodies were measured in serum and perfusion fluid from the jejunum of RA patients and healthy controls to determine the systemic and mucosal immune response.
Go to: Methods
IgG, IgA, and IgM antibodies to dietary antigens were measured in serum and jejunal perfusion fluid from 14 RA patients and 20 healthy subjects. The antigens originated from cow’s milk (α‐lactalbumin, β‐lactoglobulin, casein), cereals, hen’s egg (ovalbumin), cod fish, and pork meat.
Go to: Results
In intestinal fluid of many RA patients, all three immunoglobulin classes showed increased food specific activities. Except for IgM activity against β‐lactoglobulin, all other IgM activities were significantly increased irrespective of the total IgM level. The RA associated serum IgM antibody responses were relatively much less pronounced. Compared with IgM, the intestinal IgA activities were less consistently raised, with no significant increase against gliadin and casein.
Considerable cross reactivity of IgM and IgA antibodies was documented by absorption tests. Although intestinal IgG activity to food was quite low, it was nevertheless significantly increased against many antigens in RA patients. Three of the five RA patients treated with sulfasalazine for 16 weeks had initially raised levels of intestinal food antibodies; these became normalised after treatment, but clinical improvement was better reflected in a reduced erythrocyte sedimentation rate.
Go to: Conclusions
The production of cross reactive antibodies is strikingly increased in the gut of many RA patients. Their food related problems might reflect an adverse additive effect of multiple modest hypersensitivity reactions mediated, for instance, by immune complexes promoting autoimmune reactions in the joints.
Article Link: https://www.ncbi.nlm.nih.gov/pmc
32) The pathogenesis of rheumatoid arthritis is associated with milk or egg allergy..Li J, Yan H, Chen H, Ji Q, Huang S, Yang P, Liu Z, Yang B. North Am J Med Sci 2016;8:40-6. Learn More
BACKGROUND:
Rheumatoid arthritis (RA) is a very complicated autoimmune disease with apparent synovial hyperplasia and cartilage and bone destruction.
AIMS:
In the present study, we aimed to determine whether the pathogenesis of RA correlates with food allergy and which allergen(s) are relevant.
MATERIALS AND METHODS:
We used type-II collagen (CII) to induce arthritis (collagen-induced arthritis, CIA) model in Wistar rats, and the development of arthritis was evaluated accordingly by scoring system. Proinflammatory cytokine levels in plasma were measured by enzyme-linked immunosorbent assay (ELISA), and concentrations of circulating immune complexes (CICs) were analyzed by C1q solid phase method.
Furthermore, food-specific immunoglobulin G (IgG) and immunoglobulin E (IgE) levels were determined in the CIA model.
RESULTS:
In the CIA model, we found that levels of tumor necrosis factor-alpha (TNF-a), interleukin (IL)-1, IL-6, and IL-17, as well as CICs, were elevated significantly. Moreover, concentrations of milk- or egg-specific IgG and IgE were enhanced strikingly in CIA rats.
CONCLUSION:
The results suggest that pathogenesis of RA correlates closely to increased egg- or milk-specific antibodies.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/27011946
33) Correlation of Tissue Antibodies and Food Immune Reactivity in Randomly Selected Patient Specimens. J Lambert J, Vojdani A (2017) Clin Cell Immunol 8: 521. Doi: 10.4172/2155-9899.1000521. Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25599182
CROHN’s DISEASE
34) Higher titers of anti-Saccharomyces cerevisiae antibodies IgA and IgG are associated with more aggressive phenotypes in Romanian patients with Crohn’s disease. Gologan S1, Iacob R, Preda C,Vadan R, Cotruta B, Catuneanu AM, Iacob S, Constantinescu I, Gheorghe L, Iobagiu S, Gheorghe C, Diculescu M. J Gastrointestin Liver Dis. 2012 Mar;21(1):39-44.Learn More
The aim of the present study was to evaluate the diagnostic value of five serological antibodies, perinuclear antineutrophil cytoplasmic antibody (pANCA), anti-Saccharomyces cerevisiae antibodies [ASCA; ASCA-immunoglobulin (IgG)and ASCA-IgA], Escherichia coli outer membrane porin C antibody (anti- OmpC) and CBir1 flagellin antibody for detection in inflammatory bowel diseases.
Whether the antibody status correlated with the disease phenotype was also evaluated. Sera from 71 patients with Crohn’s disease (CD), 41 patients with ulcerative colitis (UC), 78 patients with other gastrointestinal diseases and 31 healthy control subjects were investigated. Clinical data were gathered at the time of serum sampling and enzyme-linked immunosorbent assay was used to determine titers of the above mentioned five antibodies. The pANCA test exhibited a sensitivity of 53.7% for UC and the ASCA test had a sensitivity of 66.2% for CD. The prevalence of anti-OmpC was significantly higher in CD than in intestinal tuberculosis (TB), indicating that anti-OmpC may be a serologic marker distinguishing CD from TB. The pANCA+/ASCA- exhibited the best specificity for differentiating between CD and UC. In UC, the presence of pANCA was greater in the patients with moderate to severe activity than in those with mild activity. ASCA was more positive in ileal CD. Furthermore, positive ASCA-IgG or anti-OmpC implied that complicated CD and pANCA was associated with colonic CD. Seropositivity of anti-CBir1 was lowest in colonic CD.
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4717042
35) The effects of provocation by foods with raised IgG antibodies and additives on the course of Crohn’s disease: A pilot study. Hulya Uzunismail et al. Turk J Gastroenterol 2012; 23 (1): 19-27.Learn More
BACKGROUND/AIMS:
This study was designed to assess the role of foods with raised IgG antibodies and additives on the symptoms and inflammation of Crohn’s disease.
METHODS:
Eight patients with Crohn’s disease in remission were studied. They followed a strict diet during phase I. Then, provocations with two, three-day periods (phases II and III) followed: in phase II, pure forms of foods with high IgG antibodies and in phase III, off-the-shelf forms of those foods were added. Stool samples were collected for fecal calprotectin assay. Blood samples were taken on the 11th and 17th days for highly sensitive C-reactive protein, ferritin, erythrocyte sedimentation rate, white blood cells, and platelets. Patients kept a diet-symptom diary.
RESULTS:
Increased Crohn’s disease activity index scores were found statistically significant (p=0.012) between pre- and during the provocation weeks. There were significant increases according to Harvey-Bradshaw Index when the highest values during the phases I, II (p=0.027) and I, III (p=0.027) were compared. The increases in highly sensitive C-reactive protein (p=0.025) and white blood cells (p= 0.036) were found statistically significant. Fecal calprotectin levels showed day-to-day variability. When compared, the levels of fecal calprotectin increased in all patients on the last day of the restriction (10th day) and the first day of the provocation (11th day) with the exception of one patient.
CONCLUSIONS:
Foods with raised IgG antibody levels and food additives can provoke the symptoms and may stimulate the inflammation in patients with Crohn’s disease. Addition of a proper diet with restriction of those foods may be beneficial in the medical treatment.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/22505375
36) Clinical relevance of IgG antibodies against food antigen in Crohn’s Disease – A double blind cross over diet intervention study. S. Bentz, M. Hausmann, S. Paul, W. Falk, F. Obermeier, J.Scholmerich, G. Rogler Digestion (2010);81:252–264.Learn More
BACKGROUND:
Environmental factors are thought to play an important role in the development of Crohn’s disease (CD). Immune responses against auto-antigens or food antigens may be a reason for the perpetuation of inflammation.
METHODS:
In a pilot study, 79 CD patients and 20 healthy controls were examined for food immunoglobulin G (IgG). Thereafter, the clinical relevance of these food IgG antibodies was assessed in a double-blind cross-over study with 40 patients. Based on the IgG antibodies, a nutritional intervention was planned. The interferon (IFN)gamma secretion of T cells was measured. Eosinophil-derived neurotoxin was quantified in stool.
RESULTS:
The pilot study resulted in a significant difference of IgG antibodies in serum between CD patients and healthy controls. In 84 and 83% of the patients, respectively, IgG antibodies against processed cheese and yeast were detected.
The daily stool frequency significantly decreased by 11% during a specific diet compared with a sham diet. Abdominal pain reduced and general well-being improved. IFNgamma secretion of T cells increased. No difference for eosinophil- derived neurotoxin in stool was detected.
CONCLUSION:
A nutritional intervention based on circulating IgG antibodies against food antigens showed effects with respect to stool frequency. The mechanisms by which IgG antibodies might contribute to disease activity remain to be elucidated.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/20130407
ASTHMA
37) Food-specific IgG Antibody–guided Elimination Diets Followed by Resolution of Asthma
Symptoms and Reduction in Pharmacological Interventions in Two Patients: A Case Report Kulveen Virdee,Glob Adv Health Med. 2015 Jan; 4(1): 62–66.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4311561/
38) Ovalbumin-specific immunoglobulin G and subclass responses through the first 5 years of life in relation to duration of egg sensitization and the development of asthma. Vance, G.H.S., Thornton, C.A., Bryant, T.N., Warner, J.A. and Warner, J.O. Clinical and Experimental Allergy,(2004) 34, (10), 1542-1549.Learn More
Background Egg sensitization, particularly persistent sensitization, is a risk factor for later asthma. However, little is known about accompanying IgG and subclass responses and how they might relate to asthmatic outcome.
Objective To characterize hen’s egg ovalbumin (OVA) IgG and subclass responses through the first 5 years of life in relation to duration of egg sensitization and later asthma.
Subjects and methods The subjects (n=46) formed part of a larger cohort, born to atopic parents, who had been evaluated prospectively for the development of asthma. Egg sensitization was classified as transient (positive egg skin prick test at 1 year only) or persistent (positive skin test for at least 2 years). Plasma OVA IgG, IgG1 and IgG4 concentrations at birth (cord), 6 months, 1 and 5 years of age were measured by ELISA.
Results The kinetics of OVA IgG and IgG1 responses, but not IgG4, differed between egg sensitized and non‐egg sensitized (NES) children. Only persistently sensitized children had a rise in OVA IgG1 concentration through the first year of life, and at 1 year of age they had significantly higher OVA IgG and IgG1 than either transiently sensitized or NES children. High OVA IgG1 was associated with later asthma: at 1 year of age, OVA IgG1 greater than 14 500 U predicted asthma with a sensitivity 64% and specificity 74%.
Conclusion OVA IgG and subclass responses relate to the duration of egg sensitization. Measurement of OVA IgG1 concentration in infancy might offer a useful adjunct to identify those at an increased risk of asthma.
Article Link: https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365- 2222.2004.02058.x
39) The effect of exclusion of dietary egg and milk in the managment of asthmatic children :
a pilot study. Yussof NA, Hampton SM, Dickerson JW, Morgan JB, (2004) J.R.Soc.Health 124(2) 74-80.Learn More
A seven-day assessment of food intake was made before, during and immediately after the period of dietary intervention in both groups. A blood sample was taken from each child for determination of food specific antibodies and in those children who could do so, the peak expiratory flow rate (PEFR) was measured. Based on the recommended nutrient intake (RNI), the mean percentage energy intake of the children in the experimental group was significantly lower (p < 0.05) in the experimental group. After the eight-week study period and compared with baseline values, the mean serum anti-ovalbumin IgG and anti-beta lactoglobulin IgG concentrations were statistically significantly reduced (p < 0.05) for both in the experimental group. In contrast, the values for anti-ovalbumin IgG in the control group were significantly increased and those for anti-beta lactoglobulin IgG were practically unchanged. The total IgE values were unchanged in both groups. Over the study period, the PEFR in those children in the experimental group able to perform the test was significantly increased, but no such change was noted in the children in the control group who could do the test. These results suggest that even over the short time period of eight weeks, an egg- and milk-free diet can reduce atopic symptoms and improve lung function in asthmatic children.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/15067979
BRAIN-Psychosis
40) IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in firstepisode schizophrenia. Emily G. Severance,a,* Kristin L. Gressitt,a Armin Alaedini,b Cathrin Rohleder,c Frank Enning,c,d J. Malte Bumb,c Juliane K. Muller,c Emanuel Schwarz,c Robert H. Yolken,a and F. Markus Leweke . Brain Behav Immun. 2015 Feb; 44: 148–158.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4275312/
41) The humoral response in the pathogenesis of gluten ataxia. M. Hadjivassiliou, MD, Neurology April 23, 2002 vol. 58 no. 8 1221-1226.Learn More
To characterize humoral response to cerebellum in patients with gluten ataxia.
BACKGROUND:
Gluten ataxia is a common neurologic manifestation of gluten sensitivity.
METHODS:
The authors assessed the reactivity of sera from patients with gluten ataxia (13), newly diagnosed patients with celiac disease without neurologic dysfunction (24), patients with other causes of cerebellar degeneration (11), and healthy control subjects (17) using indirect immunocytochemistry on human cerebellar and rat CNS tissue. Cross-reactivity of a commercial IgG antigliadin antibody with human cerebellar tissue also was studied.
RESULTS:
Sera from 12 of 13 patients with gluten ataxia stained Purkinje cells strongly. Less intense staining was seen in some but not all sera from patients with newly diagnosed celiac disease without neurologic dysfunction. At high dilutions (1:800) staining was seen only with sera from patients with gluten ataxia but not in control subjects. Sera from patients with gluten ataxia also stained some brainstem and cortical neurons in rat CNS tissue. Commercial anti-gliadin antibody stained human Purkinje cells in a similar manner. Adsorption of the antigliadin antibodies using crude gliadin abolished the staining in patients with celiac disease without neurologic dysfunction, but not in those with gluten ataxia.
CONCLUSIONS:
Patients with gluten ataxia have antibodies against Purkinje cells. Antigliadin antibodies cross-react with epitopes on Purkinje cells.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/11971090
42) Disruption in the Blood-Brain Barrier: The Missing Link between Brain and Body Inflammation in Bipolar Disorder? Jay P. Patel1 and Benicio N. Frey Neural Plasticity Volume 2015, Article ID 708306, 12 pages.Learn More
The potential implications for research in this area and directions for future studies are discussed.
43) The role of IgG hypersensitivity in the pathogenesis and therapy of depressive disorders.
Karakuła-Juchnowicz H, Szachta P, Opolska A, Morylowska-Topolska J, Gałęcka M, Juchnowicz D, Krukow P, Lasik Z. Nutr Neurosci. 2014 Sep 30.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25268936
44) Evidence for an immune response in major depression: a review and hypothesis.Maes M. Progress in Neuro-Psychopharmacology and Biological Psychiatry 1995 Volume 19, Issue1, Pages11-38.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/7708925
45) Subunit and whole molecule specificity of the anti-bovine casein immune response in recent onsetpsychosis and schizophrenia. Severance EG, Dickerson FB, Halling M, Krivogorsky B, Haile L, Yang S, Stallings CR, Origoni AE, Bossis I, Xiao J, Dupont D, Haasnoot W, Yolken RH. Schizophr Res. 2010 May;118(1-3):240-7Learn More
46) Association between bovine casein antibody and new onset schizophrenia among US military personnel. Niehbur DW, Li Y, Cowan DN, Weber NS, Fisher JA, Ford GM, Yolken R. (2011) Schizophr.Res. Mar2. (Epub ahead of print.Learn More
Among schizophrenic patients, it is assumed that at least 30% will not respond to conventional antipsychotics (2). These data underlie the importance of precision medicine in psychiatry, in other words, the need to identify subgroups of patients with specific signatures who will benefit from treatment targeting these specific biological pathways. Reviving an area of exploration older than a century, recent and abundant literature emphasized the importance of the immune system in the pathophysiology of schizophrenia [for review, see Ref. (3)].
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5396186/
47) Complement C1q formation of immune complexes with milk caseins and wheat glutens in
Schizophrenia. Emily G. Severancea, Kristin Gressitta, Meredith Hallinga, Cassie R. Stallingsb, Andrea E. Origonib, Crystal Vaughanb, Sunil Khushalanib, Armin Alaedinic, Didier Dupontd, Faith B. Dickersonb, and Robert H. Yolkena Neurobiol Dis. 2012 December ; 48(3): 447–453.Learn More
Thirteen schizophrenics were given gluten-free peanut-flour supplementary cookies and 13 were given virtually identical cookies with gluten added. Tests and rating scales before and after the ten-day study period showed no greater improvement for those receiving the gluten-free cookies than for those receiving the gluten-added cookies. Contrary to expectations, the group receiving gluten- added cookies showed significantly greater improvement of Profile on Mood States measures of tension-anxiety and anger-hostility. Previous findings were not supported. Perhaps a longer time on the diet is required for any beneficial effects to appear.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/7065842
48) Dietary antigens, epitope recognition, and immune complex formation in recent onset psychosis and long-term schizophrenia. Severance EG1, Lin J, Sampson HA, Gimenez G, Dickerson FB, Halling M, Gressitt K, Haile L,Stallings CR, Origoni AE, Dupont D, Yolken RH.Schizophr Res. 2011 Mar;126(1-3):43-50.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/21211944
49) Seroreactive marker for inflammatory bowel disease and associations with antibodies to dietary proteins in bipolar disorder. Emily G. Severancea, Kristin L. Gressitta, Shuojia Yanga, Cassie R. Stallingsb, Andrea E. Origonib, Crystal Vaughanb, Sunil Khushalanib, Armin Alaedinic, Faith B. Dickersonb, and Robert H. YolkenaBipolar Disord. 2014 May ; 16(3):230–240.Learn More
Immune sensitivity to wheat glutens and bovine milk caseins may affect a subset of individuals with bipolar disorder. Digested byproducts of these foods are exorphins that have the potential to impact brain physiology through action at opioid receptors. Inflammation in the gastrointestinal (GI) tract might accelerate exposure of food antigens to systemic circulation and help explain elevated gluten and casein antibody levels in individuals with bipolar disorder.
Go to: Methods
We measured a marker of GI inflammation, anti-Saccharomyces cerevisiae antibodies (ASCA), in non-psychiatric controls (n=207), bipolar disorder without a recent onset of psychosis (n=226), and bipolar disorder with a recent onset of psychosis (n=38). We compared ASCA levels to antibodies against gluten, casein, EBV, HSV-1, Influenza A, Influenza B, measles, and Toxoplasma gondii.
Go to: Results
Elevated ASCA conferred a 3.5 to 4.4-fold increased odds ratio of disease association (age-, race- and gender-corrected multinomial logistic regressions, p≤0.00001) that was independent of type of medication received. ASCA correlated with food antibodies in both bipolar groups (R2=0.29–0.59, p≤0.0005), and with measles and T. gondii IgG in the recent onset psychosis bipolar disorder group (R2=0.31–0.36, p≤0.004–0.01).
Go to: Conclusions
Elevated seropositivity of a GI-related marker and its association with antibodies to food-derived proteins and self-reported GI symptoms suggests a GI comorbidity in at least a subgroup of individuals with bipolar disorder. Marker seroreactivity may also represent part of an overall heightened activated immune state inherent to this mood disorder.
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075657/
50) Gastrointestinal inflammation and associated immune activation in schizophrenia.
Emily G. Severancea, Armin Alaedinib, Shuojia Yanga, Meredith Hallinga, Kristin L. Gressitta, Cassie R. Stallingsc, Andrea E. Origonic, Crystal Vaughanc, Sunil Khushalanid, F. Markus Leweked,e, Faith B. Dickersonc, and Robert H. Yolkena Schizophr Res. 2012 June ; 138(1): 48–53.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4244845/
51)Breaking down the barriers: the gut microbiome, intestinal permeability and stress-related psychiatric disorders. John R. Kelly,Paul J.,.John F. Cryan, Timothy G. Dinan, Gerard Clarke, Niall P. Hyland Front. Cell. Neurosci., 14 October 2015 Learn More
We will draw on both clinical and preclinical evidence to support this concept as well as the key features of the gut microbiota which are necessary for normal intestinal barrier function.
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4604320/
52)Gut Uptake, Brain and Behaviour Tveiten D. Bioeng1 and K. L. Reichelt Journal of Scientific Research &Reports 3(22): 2834-2847, 2014;Learn More
Aims: To document the evidence for a gut uptake to brain axis. The many hormones, many of them peptides and shared by the intestines and the brain, will not be included in this survey.
Methods: Systematic looking through journal publications by means of Pub med and collected information and authors research since 1978.
Results: Food-protein antibodies, food-protein derived peptides and direct physiological evidence point to considerable effect of the digestive system on behavior and mood. Removal of specific proteins from diet ameliorates the clinical condition.
Conclusion: Uptake from the gut of various substances has effect on behaviour.
Article Link: http://www.sciencedomain.org/abstract/5959
Excema
53) Circulating immunoglobulins, leucocytes and complements in childhood-onset atopic eczema. Hon KL1, Wang SS, Pong NH, Leung TF.Indian J Pediatr. 2013 Feb;80(2):128-31. Learn More
To evaluate if eczema severity is associated with blood levels of immunoglobulins, white cell differentials and complements.
METHODS:
White cell differentials, levels of serum immunoglobulins and complements of patients with eczema and miscellaneous non-eczema skin diseases were measured. Eczema severity and quality of life were assessed by SCORAD, Nottingham Eczema Severity Score (NESS) and Children’s Dermatology Life Quality Index (CDLQI). Correlations were analyzed by Pearson’s correlation test for parametric data and Spearman’s rho correlation test for non-parametric data.
RESULTS:
Serum IgE and peripheral blood eosinophil percentage were significantly higher in patients with eczema than other non-eczema skin diseases. Levels of IgE (log- transformed), IgA and IgG correlated with objective SCORAD (r = 0.52, 0.40, 0.29, respectively). Levels of eosinophil, neutrophils, lymphocytes and complements also correlated with objective SCORAD, with the eosinohil/lymphocyte ratio showing the highest correlation (r = 0.60, p < 0.01).
Ratios of IgE/IgA, IgE/IgG, eosinophils/lymphocytes, eosinophils/neutrophils correlated positively with CDLQI. IgM appeared to have no correlation with eczema.
CONCLUSIONS:
Blood levels of IgE, IgA, IgG,eosinophils, lymphocytes, neutrophils and complements pathophysiologically correlate with eczema severity.
Eosinophil/lymphocyte ratio may represent a readily-available objective laboratory correlate of eczema severity. Eczema is a complex atopic disease involving many cellular and humoral components of the immune system.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/22706909
OBESITY
54) Baker’s yeast (Saccharomyces cerevisiae) antigen in obese and normal weight subjects. Salamati S1, Martins C, Kulseng B. Clin Obes. 2015 Feb;5(1):42-7.Learn More
measured by enzyme-linked immunosorbent assay. More than one-third of the obese individual (35%) showed elevated titres of ASCA compared with the control group (5%). This antibody was positively associated with weight (P = 0.01), BMI (P = 0.02) and waist circumference (P = 0.02), but not with C-reactive protein. It seems that ASCA are not only specific for CD but are also associated with obesity. S. cerevisiae or a related antigen may play a role in the matrix of this complex condition.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/25611585
55) IgG Receptor FcγRIIB Plays a Key Role in Obesity-Induced Hypertension.
Nathan C. Sundgren, Wanpen Vongpatanasin, Brigid-Meghan D. Boggan, Keiji Tanigaki, Ivan S. Yuhanna, Ken L. Chambliss, Chieko Mineo, and Philip W. Shaul Hypertension. 2015 February ; 65(2): 456–462.Learn More
Article Link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4419357/
56) Antibodies against food antigens are correlated with inflammation and intima media thickness in obese juveniles. Wilders-Truschnig M, Mangge H, Lieners C, Gruber HJ, Mayer C and Marz W. IgG.(2007). Exp Clin Endocrinol Diabetes.Learn More
Systemic low grade inflammation may contribute to the development of obesity, insulin resistance, diabetes mellitus and atherosclerotic vascular disease. Food intolerance reflected by immunoglobulin G (IgG) antibodies may predispose to low grade inflammation and atherogenesis. We examined the relationship between IgG antibodies specific for food components, low grade inflammation and early atherosclerotic lesions in obese and normal weight juveniles.
RESEARCH METHODS AND PROCEDURES:
We determined IgG antibodies directed against food antigens, C-reactive protein (CRP) and the thickness of the intima media layer (IMT) of the carotid arteries in 30 obese children and in 30 normal weight children.
RESULTS:
Obese juveniles showed a highly significant increase in IMT (p=0.0001), elevated CRP values (p=0.0001) and anti-food IgG antibody concentrations (p=0.0001) compared to normal weight juveniles. Anti-food IgG showed tight correlations with CRP (p=0.001/r=0.546) and IMT (p=0.0001/r=0.513) and sustained highly significant in a multiple regression model.
DISCUSSION:
We show here, that obese children have significantly higher IgG antibody values directed against food antigens than normal weight children. Anti- food IgG antibodies are tightly associated with low grade systemic inflammation and with the IMT of the common carotid arteries. These findings raise the possibility, that anti-food IgG is pathogenetically involved in the development of obesity and atherosclerosis.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/18072008
57) Increase adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. Hotamisligil G. S., Arner P., Caro J. F., Atkinson R. L., Spiegelman B. M.. J Clin Invest (1995); 95: 2409-2415.Learn More
These results suggest a role for the abnormal regulation of this cytokine in the pathogenesis of obesity-related insulin resistance.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/7738205
58) Adipose expression of tumor necrosis factor- direct role in obesity-linked insulin resistance. Hotamisligil G. S., Shargill N. S., Spiegelman B. M.. Science (1993); 259: 87-91.Learn More
These results indicate a role for TNF-alpha in obesity and particularly in the insulin resistance and diabetes that often accompany obesity
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/7678183
Autism
59) Food allergy investigations and ist significance in autism spectrum disorders. Anath N Rao, Minakshi Koch, Sabyasachi Ghosh and Suresh Kumar V. International Journal of Pharma and Bio Sciences Vol.1/Issue-4/Oct-Dec.2010.Learn More
with typical forms of autism to attention deficits frequently have sensitivities to certain foods. A food
allergy is an IgE or IgG mediated reaction which shows symptoms within hours of having ingested the
food. In the Department of Metabolic Diseases and Research, Apollo Hospital, serum samples of
children, clinically diagnosed with Autism Spectrum Disorders (ASD) using DSM IV criteria, were
tested for food allergy (IgE) on commonly used foods / food stuffs in a typical Indian cooking or form a
part of the diet. We, in this study have attempted to demonstrate that the immediate or IgE mediated
food allergy pattern is easily recognizable and anti-gliadin IgG in ASD studies is valuable.
Improvement is seen with foods free from allergens recognized on the IgG/ IgE based investigation
leading to speculation about a high prevalence of food allergy in ASD children
60) Antibodies against Food Antigens in Patients with Autistic Spectrum Disorders. Laura de Magistris, Annarita Picardi, Dario Siniscalco, Maria Pia Riccio, Anna Sapone, Rita Cariello, Salvatore Abbadessa, Nicola Medici, Karen M. Lammers, Chiara Schiraldi, Patrizia Iardino, Rosa Marotta, Carlo Tolone, Alessio Fasano, Antonio Pascotto, and Carmela Bravaccio BioMed Research International Volume 2013, Article ID 729349, 11 pages.Learn More
Immune system of some autistic patients could be abnormally triggered by gluten/casein assumption. The prevalence of antibodies to gliadin and milk proteins in autistic children with paired/impaired intestinal permeability and under dietary regimen either regular or restricted is reported.
METHODS:
162 ASDs and 44 healthy children were investigated for intestinal permeability, tissue-transglutaminase (tTG), anti-endomysium antibodies (EMA)-IgA, and total mucosal IgA to exclude celiac disease; HLA-DQ2/-DQ8 haplotypes; total systemic antibodies (IgA, IgG, and IgE); specific systemic antibodies: α-gliadin (AGA-IgA and IgG), deamidated-gliadin-peptide (DGP-IgA and IgG), total specific gliadin IgG (all fractions: α, β, γ, and ω), β-lactoglobulin IgG, α-lactalbumin IgG, casein IgG; and milk IgE, casein IgE, gluten IgE,-lactoglobulin IgE, and α-lactalbumin IgE.
RESULTS:
AGA-IgG and DPG-IgG titers resulted to be higher in ASDs compared to controls and are only partially influenced by diet regimen. Casein IgG titers resulted to be more frequently and significantly higher in ASDs than in controls. Intestinal permeability was increased in 25.6% of ASDs compared to 2.3% of healthy children. Systemic antibodies production was not influenced by paired/impaired intestinal permeability.
CONCLUSIONS:
Immune system of a subgroup of ASDs is triggered by gluten and casein; this could be related either to AGA, DPG, and Casein IgG elevated production or to impaired intestinal barrier function.
Article Link: https://www.ncbi.nlm.nih.gov/pubmed/23984403