TO THE EDITOR:
In the recent study of Cai et al. (1), the prevalence and clinical significance of 14 food-specific immunoglobulin G (IgG) antibodies in patients with inflammatory bowel disease (IBD) were investigated. While patients with IBD had significantly higher prevalence of IgG antibodies as compared to the the healthy controls, no marked differences were observed between the patients with Crohn’s disease (CD) and ulcerative colitis (UC). Five years ago, we studied food-specific IgG antibodies in 26 CD (17 F ) and 25 UC (14 F) patients, and we detected that some foods showed significantly increased rates in patients with CD as compared to those with UC.
IgG antibodies were detected using a commercially available enzyme linked immunosorbent assay(ELISA) test (ImuPro 300 test) against more than 260 food and additive antigens. As, we were unable to carry out a statistical analysis for every antigen present in the panel, we evaluated only 32 foods and 3 additives (agar [E406], guar gum [E412] and citric acide) which were chosen through certain criteria. Many of the foods that are frequently utilized but rarely caused increased IgG levels in both disorders such as potato, onion, olive, lamb, black tea, apple, orange, apricot, carrot, green bean, banana, cherry, spinach, lentils, curled kale, leek, beetroot, courgette, as well as foods which are rarely consumed in our country such as pork, crab and shrimp were excluded from the statistical analysis. Therefore, we had only nine foods comparable with those in the study of Cai et al. which were egg, rice, corn, tomato, milk, chicken, beef, mushroom and wheat. Similar to their study, we found no significant differences between the two disorders with regard to the prevalences of these 9 food-specific IgG antibodies.
On the other hand, positivity of yeast IgG antibody was detected in 16 patients with CD (61.5%), and in 2 patients with UC (8%) (p=0001). In the panel, yeast antigen belongs to the Saccharomyces cerevisiae which is used in the making of bread and beer. IgG antibodies against this kind of yeast are the same ASCA IgG antibodies and it is a well-known fact that their prevalance differ in CD and UC . Although beer is not a common drink, bread is the main food in our country and consumed at least three times a day. Pistachio (p=0.005), garlic (p=0.004), poppy seeds (p=0.017), pineapple (p=0.03), gluten (p=0.032), sunflower seed (p=0.039), and honey (p=0.048) are the other foods that produce a significantly higher prevalance of IgG antibody positivity in CD patients than in UC patients. Similar to the study of Cai et al, our findings did not show a statistically significant difference between the two groups with regard to whole-wheat, however, gluten exhibited a difference. All the above listed foods, with the exception of poppy seed and pistachio, are commonly consumed in our country. The food antigens revealing significant differences in our study had not been investigated in their study.
In their study, the most common 5 foods that raised the IgG antibody prevalence were egg (73.3%), rice (%56.7), corn (56.7%), tomato (46.7%), and soybean (43.3%) in patients with CD, and egg (81%), rice (14.3%), corn (14.3%), tomato (9.5%) and milk (9.5%) in patients with UC. In our study, the prevalences of these foods in patients with CD were 50%, 19.2%, 30.8%, 23.1%, and 11.5%, respectively, whereas the same rates for patients with UC were 44%, 16%, 8%, 4% and 24%, respectively. The most common foods or additives that increased IgG antibody levels in our CD patients were whole-wheat (65.4%), poppy seed (65.4%), agar(65.4%), yeast (61.5), egg (50%) and guar gum (50%). The most common five foods and additives that raised IgG antibody prevalance in patients with UC were vanilla (48%), egg(44%), linseed (44%), whole-wheat (40%) and agar (40%). Linseed and vanilla also showed a positivity rate of 46.2% and 42.3%, respectively, in patients with CD.
Interestingly, different mushroom species yielded different results. For example, while one type had increased IgG levels in only one patient in each disease group, another type with a rare consumption record showed increased levels in 11 patients with CD and in 7 patients with UC. These results suggest that increases in food-specific IgG antibody levels are not associated with high consumption frequencies, but rather occur due to antigenicity of foods.
Food-specific IgG antibodies are naturally present in healthy persons in the form of IgG1 and frequently IgG4 sublasses, (2). Many authors consider that elevated food-specific IgG antibody levels are associated with physiological immune responses and they play an important role in allergen-specific tolerance (3). Immunotherapy studies also support the protective role of food-specific IgG antibodies, especially IgG4, in patients with food allergy (4, 5). On the other hand, diets excluding foods that increase specific IgG or IgG4 antibody concentrations produce promising results in patients with IBS (6-10), migraine ( 10-12), chronic diarrhea ( 13) and CD ( 14, 15 ). In CD, food restriction according to IgG4 antibodies results in symptomatic improvements and decreased ESR (15). In addition, provocation by IgG antibody-positive foods causes symptomatic deterioration and statistically significant increases in inflammatory markers such as WBC and hsCRP in patients with CD in remission (16). Currently, these contentious findings can not be explained completely, requiring further more detailed studies.
Our results show that IgG antibodies increase not only against common and rarely consumed foods, but also against ingredients such as yeast, vanilla and food additives in patients with IBD. Generally, the number of food additives are high and approximated to be more than 300 depending on the related country, therefore, detecting IgG antibodies against them does not appear to be feasible. Furthermore, their intake can be prevented largely by avoiding off-the-shelf foods and drinks. On the other hand, while prescribing a successful and practical elimination diet, it will be better to test 80-100 food antigens containing alternatives for some foods based on the dietary characteristics of each country.
Regards
1-Cai C, Shen J, Zhao D, Qiao Y, Xu A, et al. Serological investigation of food specific immunoglobulin g antibodies in patients with inflammatory bowel diseases. PLoS One. 2014; 9(11):e112154. doi: 10.1371/journal.pone.0112154.
2- Husby S, Oxelius VA, Teisner B, Jensenius JC, Svehag SE. Humoral immunity to dietary antigens in healthy adults. Occurrence, isotype and IgG subclass distribution of serum antibodies to protein antigens. Int Arch Allergy Appl Immunol. 1985; 77:416-22.

3- Hofmaier S, Comberiati P, Matricardi PM. Immunoglobulin G in IgE-mediated allergy and allergen-specific immunotherapy. Eur Ann Allergy Clin Immunol. 2014; 46:6-11.

4- Vidarsson G, Dekkers G, Rispens T. IgG subclasses and allotypes: from structure to effector functions. Front Immunol. 2014;20;5:520.

5- Wang J, Sampson HA. Oral and sublingual immunotherapy for food allergy. Asian Pac J Allergy Immunol. 2013;31:198-209.

6- Atkinson W, Sheldon TA, Shaath N, Whorwell PJ. Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut 2004; 53: 1459–1464 .
7-Zar S, Mincher L, Benson MJ, Kumar D. Food-specific IgG4 antibody-guided exclusion diet improves symptoms and rectal compliance in irritable bowel syndrome. Scand J Gastroenterol. 2005; 40:800-7.
8-Yang CM, Li YQ . The therapeutic effects of elimination allergic foods according to food-specific IgG antibodies in irritable bowel syndrome. Zhonghua Nei Ke Za Zhi. 2007; 46:641-3.
9-Guo H, Jiang T, Wang J, Chang Y, Guo H, Zhang W. The value of eliminating foods according to food specific immunoglobulin G antibodies in irritable bowel syndrome with diarrhea. J Int Med Res. 2012; 40:204-10.
10-Aydinlar EI, Dikmen PY, Tiftikci A, Saruc M, Aksu M, et al. IgG-based elimination diet in migraine plus irritable bowel syndrome. Headache 2013; 53:514-25.
11- Arroyave Hernández CM, Echavarría Pinto M, Hernández Montiel HL. Food allergy mediated by IgG antibodies associated with migraine in adults.
Rev Alerg Mex. 2007;54:162-8.
12-Alpay K, Ertas M, Orhan EK, Ustay DK, Lieners C, et al. Diet restriction in migraine, based on IgG against foods: a clinical double-blind, randomised, cross-over trial. Cephalalgia 2010;30:829-37.
13- Ou-Yang WX, You JY, Duan BP, Chen CB. Application of food allergens specific IgG antibody detection in chronic diarrhea in children. Zhongguo Dang Dai Er Ke Za Zhi. 2008; 10:21-4.
14- Bentz S, Hausmann M, Piberger H, Kellermeier S, Paul S. Clinical relevance of IgG antibodies against food antigens in Crohn's disease: a double-blind cross-over diet intervention study. Digestion 2010;81:252-64.
15- Rajendran N, Kumar D. Food-specific IgG4-guided exclusion diets improve symptoms in Crohn's disease: a pilot study. Colorectal Dis. 2011; 13:1009-13.

16- Uzunısmaıl H, Cengız M, Uzun H, Ozbakir F, Göksel S, et al. 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.

Hulya Uzunismail*, Fatma Özbakır**, Penbe Çağatay***

*Retired from Division of Gastroenterology, Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul
** Division of Rheumatology , Department of Medicine, Cerrahpasa Medical Faculty, University of Istanbul
*** Medical Services and Techniques Department, University of Istanbul

Correspondence to Hulya Uzunismail, Ataköy 4. Kısım. S blok 202/32 Bakırköy/Istanbul, Turkey; hulyauzunismail @ gmail.com