Food-specific IgGs Are Highly Increased in the Sera of Patients with Inflammatory Bowel Disease and Are Clinically Relevant to the Pathogenesis

Abstract

Objective Dietary antigens are common luminal antigens in the gastrointestinal tract and have been considered to contribute to the pathogenesis of inflammatory bowel disease (IBD). We analyzed the levels of food-specific IgGs against a variety of dietary antigens, explored the clinical relevance of food allergy to the pathogenesis of IBD, and investigated whether or not infliximab (IFX) treatment could regulate the immune responses induced by dietary antigens. Methods A total of 301 IBD patients, including 201 patients with Crohn's disease (CD) and 100 patients with ulcerative colitis (UC), were recruited, and their serum food-specific IgGs against 14 food antigens were detected by a semi-quantitative enzyme linked immunosorbent assay (ELISA). Total serum IgG and IgE levels were measured by immunonephelometry and fluorescent enzyme immunoassay, respectively. Simultaneously, the relevant medical records and clinical data were collected for further analyses. Results Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean antigens were found to be significantly increased in the sera of CD patients compared with UC patients and healthy controls (p<0.01). The levels of total serum IgG and IgE were also significantly higher in CD patients than in healthy controls (p<0.01). The titers of corn- and tomato-specific IgGs were found to be significantly correlated with total serum IgG in CD patients (p<0.05), while the titers of egg-, milk-, and wheat-specific IgGs were correlated with total serum IgE (p<0.05). Interestingly, IFX therapy was able to down-regulate the food-specific IgG-mediated immune response markedly in active CD patients. Conclusion Food-specific IgGs against egg, milk, wheat, corn, rice, tomato, codfish, and soybean are highly increased in the sera of CD patients. IFX treatment was able to down-regulate the levels of food-specific IgGs by suppressing intestinal inflammation and promoting mucosal healing. Therefore, food-specific IgGs may serve as an important approach in the diagnosis and management of food allergy in IBD.

Keywords: food antigens; food-specific IgGs; inflammatory bowel disease; total serum IgE; total serum IgG.

Figure 1.

The levels of food-specific IgGs against 8 common daily foods increased markedly in CD patients. A comparison of food-specific IgGs against corn, codfish, and soybean (A); milk, mushroom, and pork (B); rice, crab, and wheat (C); shrimp, chicken, and beef (D); and egg and tomato (E) between CD patients, UC patients, and HCs. **p<0.01. CD: Crohn’s disease, UC: ulcerative colitis, HCs: healthy controls

Figure 2.

Classification of IBD patients and HCs. A linear discriminant analysis revealed a weighted linear combination of the 14 “independent variables” (all food-specific IgGs against 14 food antigens) where the three groups (CD, UC and HCs) differed as much as possible. IBD: inflammatory bowel disease

Figure 3.

The presence of cross-reactive antigen epitopes between food antigens. A dendrogram of all food-specific IgG data. The dendrogram was developed using the Ward method of clustering to show food antigens that elicited similar immune responses in IBD patients and HCs.

Figure 4.

A comparison of the total serum IgG and IgE levels between CD patients, UC patients, and HCs. The levels of serum IgG and IgE were determined using the method indicated. A: Total serum IgG levels in CD patients (n=131), UC patients (n=53), and HCs (n=61). B: Total serum IgE levels in CD patients (n=126), UC patients (n=43), and HCs (n=50). **p<0.01 CD.

Figure 5.

Infliximab (IFX) therapy induces clinical remission and promotes intestinal mucosal healing in CD patients. The levels of ESR (A), CRP (B), Alb (C), Hb (D), and SES-CD (E) were determined in IFX-treated patients with active CD before and after IFX treatment, as described in the Materials and Methods. **p<0.01 compared with those before IFX treatment. CD: Crohn’s disease, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, Alb: albumin, Hb: hemoglobin, SES-CD: simple endoscopic score for CD