title: Antibodies to food antigens in Japanese patients with type 1 diabetes mellitus.
abstract: To examine humoral and mucosal immune responses to food antigens and their relation to the pathophysiology of type 1 diabetes mellitus, IgA and IgG antibodies to cow's milk antigens (bovine serum albumin (BSA) and beta-lactoglobulin (BLG)) and another food antigen (ovalbumin, (OVA)) in human serum were assessed by enzyme-linked immunosorbent assay (ELISA). If anti-idiotype antibodies to the antibodies were present in serum, they might interfere with the ELISA assay, so suitable microtiter plates were employed to minimize such interference. The levels of IgA and IgG antibodies to the above antigens (P<0.001-P<0.01) and the prevalence of positive sera (P<0.001-P<0.05) in the patient group (n=52, aged 14.5+/-4.1 (S.D.) years) were significantly higher than those in the control group (n=41, aged 13.3+/-6.8 (S.D.) years). Interestingly, the levels of IgA antibodies to all the food antigens examined were elevated in 26 (50%) patients, while the elevation was seen in 3 (7%) healthy controls. The elevation of IgA antibodies in the patients was well correlated with increased concentrations of IgA and transforming growth factor (TGF)-beta, which induces IgA-producing B-cells, in serum. Although the cytokine TGF-beta is secreted from regulatory T-cells (Th3), and is related to oral tolerance, the interleukin-2 (IL-2, Th1)/IL-4 (Th2) ratio in the patient group was significantly elevated (P<0.001), which might indicate that the oral tolerance is impaired in patients. Thus, we demonstrated that both IgA and IgG antibodies to several food antigens are elevated in patients. We suggest that impairment of oral tolerance might be related to the pathogenesis of type 1 diabetes mellitus.
authors.affiliation: Department of Environmental Health Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, 573-0101, Osaka, Japan. kohno@pharm.setsunan.ac.jp
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Kohno
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kobashiri
authors.forename: Yohko
authors.initials: Y
authors.lastname: Sugie
authors.forename: Shigehisa
authors.initials: S
authors.lastname: Takai
authors.forename: Kazuhito
authors.initials: K
authors.lastname: Watabe
authors.forename: Yukikazu
authors.initials: Y
authors.lastname: Kaino
authors.forename: Kaichi
authors.initials: K
authors.lastname: Kida
mesh_terms: D000293:Adolescent; D000818:Animals; D044466:Asian People; D002417:Cattle; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000276:immunology*; D005260:Female; D005502:Food; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood*; D007074:Immunoglobulin G / Q000097:blood*; D007564:Japan; D008297:Male; D008892:Milk / Q000276:immunology*; D012016:Reference Values; D012710:Serum Albumin, Bovine / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000097:blood
chemical_list: D007070:Immunoglobulin A; D007074:Immunoglobulin G; D016212:Transforming Growth Factor beta; D012710:Serum Albumin, Bovine