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BMC Gastroenterology

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IgG and IgG4 antibodies in subjects with irritable bowel syndrome: a case control study in the general population

BMC Gastroenterology201212:166

https://doi.org/10.1186/1471-230X-12-166

Received: 8 June 2012

Accepted: 14 November 2012

Published: 21 November 2012

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Archived Comments

  1. IgG levels to food correlate with nutritional exposure to food antigens but a methodological weakness of this research prevents the recognition of Yeast-related foods as a possible cause of Irritable Bowel Syndrome (IBS).

    20 February 2014

    Attilio Francesco Speciani, GEK srl

    Dear Editor,

    We appreciated the aim of the study by Ligaarden et al. (1) to take on a difficult clinical syndrome and even the more difficult immune landscape associated with irritable bowel syndrome (IBS). Yet, we believe that the reported results are biased by some major methodological weaknesses.

    The first one derives by the limited nutritional profile of IBS patients and controls analyzed by this work. For instance, sugar was considered only according to its direct amount in fruits, berries, juices and carbonated beverages, whereas it was not included in complex foods like cookies and most of the supermarket preserved foods, from peanut butter to minced red meat.

    Even worse, strong antigenic foods like red meat and wheat had been excluded from food frequency questionnaire a priori. In fact most of cereals are assumed in diet as fermented end products (bread, cakes, pizza etc.).The second limitation emerges from the fact that food antigens were singled out as individual components of diet and not grouped and summed into clusters of foods sharing common major antigens.

    Finally, the analysis of one of the major causes of IBS, intolerance to yeasts, had been limited to the quest for Candida albicans, and Saccharomyces cerevisiae antigens. Yeast and fermented foods could be of interest in determining IgG production, and those considered by the study are not the only yeast involved in gastrointestinal diseases. Other IgG antibodies against yeasts such as Aspergillus, Pennicillium, Alternaria etc. can be even associated with inflammatory bowels diseases such as Crohn’s disease and ulcerative colitis (2).

    Among the whole array of fermented foods (bread, biscuits, dairy products yogurt, etc) only alcohol was retained as representative by this study. Possible inaccuracy due to the food questionnaire had been acknowledged by the authors. However, this limitation was not extended to its possible consequences. The authors consider only the intake of sugar as a possible inducer of candida proliferation, whereas in our experience (3) the effect of fermented food such as bread, yogurt, biscuits, vinegar and so on could also have clinical significance, being also relevant in increasing the levels of IgG antibodies.

    The reported results were not discussed thoroughly to explain the possible reasons of the opposite findings published by other groups, among them Bentz et al.(4), Shulman et al. (5). Biesiekierski et al. (6), Uzunsmal et al. (7).

    All these latter works reported an association between IgG and inflammatory conditions ranging from Chron’s disease to non celiac gluten sensitivity.In conclusion, we strongly agree that IgG levels might correlate with level of exposure to food antigens. Yet, the amount of IgG production induced by clusters of food, not by each specific food, might sum up to activate the non IgE-mediated alternative systemic anaphylaxis pathway (8,9), involving total IgG, Fc gamma RIII, macrophages, PAF and BAFF, and other members of TNF family (10, 11).

    The methodological bias we described in this letter might explain why this complex and interesting work fell short of identifying this process and possibly came to partially wrong conclusions.

     

    Attilio Francesco Speciani MD, GEK - Food Inflammation Dept, Milan Italy 

    Gabriele Piuri MD, SMA - Associated Medical Services,  Milan (Italy) 

    Enrico Ferrazzi MD Chairman Dept. of Woman, Mother and Neonate, Biomedical and Clinical Sciences School of Medicine, University of Milan (Italy) 

     

    Bibliography

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    2. Dotan I, Fishman S, Dgani Y, Schwartz M, Karban A, Lerner A, Weishauss O, Spector L, Shtevi A, Altstock RT, Dotan N, Halpern Z: Antibodies against laminaribioside and chitobioside are novel serologic markers in Crohn's disease. Gastroenterology 2006, 131:366–378.

    3. Speciani AF, Chiozzi V, Cetin I, Piuri G, De Lucchi L, Bozzo G: Successful treatment of recurrent candidiasis with yeast-reducing diet and induction of low-dose tolerance towards fungal agents.Allergy 2009, 64:502–503.

    4. Bentz S, Hausmann M, Piberger H, Kellermeier S, Paul S, Held L, Falk W, Obermeier F, Fried M, Schölmerich J, Rogler G: Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a double-blind cross-over diet intervention study. Digestion 2010, 81:252–264.

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    7. Uzunısmaıl H, Cengız M, Uzun H, Ozbakir F, Göksel S, Demırda? F, Can G, Balci H: The effects of provocation by foods with raised IgG antibodies and additives on the course of Crohn's disease: a pilot study. Turk J Gastroenterol 2012, 23:19–27.

    8. Finkelman FD: Anaphylaxis: lessons from mouse models. J Allergy Clin Immunol 2007, 120:506–15– quiz 516–7.

    9. Khodoun MV, Strait R, Armstrong L, Yanase N, Finkelman FD: Identification of markers that distinguish IgE- from IgG-mediated anaphylaxis. Proc Natl Acad Sci USA 2011, 108:12413–12418.

    10. Lied GA, Lillestøl K, Valeur J, Berstad A: Intestinal B cell-activating factor: an indicator of non-IgE-mediated hypersensitivity reactions to food? Aliment Pharmacol Ther 2010, 32:66–73.

    11. Lied GA, Berstad A: Functional and clinical aspects of the B-cell-activating factor (BAFF): a narrative review. Scand J Immunol 2011, 73:1–7.

    Competing interests

    None.

Authors’ Affiliations

(1)
Department of Medicine, Innlandet Hospital Trust
(2)
Unit for Applied Clinical Research, Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology
(3)
Regional Centre for Child and Adolescent Mental Health (RBUP), Department of Neuroscience, Norwegian University of Science and Technology
(4)
Department of Research, Innlandet Hospital Trust

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