Antibodies to food antigens in Japanese patients with type 1 diabetes mellitus

Kohno, Takeyuki; Kobashiri, Yasuyuki; Sugie, Yohko; Takai, Shigehisa; Watabe, Kazuhito; Kaino, Yukikazu; Kida, Kaichi

« Previous Next »Diabetes Research and Clinical Practice
Volume 55, Issue 1 , Pages 1-9, January 2002

Antibodies to food antigens in Japanese patients with type 1 diabetes mellitus

Takeyuki Kohno
- Department of Environmental Health Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
- Corresponding author. Tel.: +81-72-8663113; fax: +81-72-8507020
Yasuyuki Kobashiri
- Department of Environmental Health Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Yohko Sugie
- Laboratory of Diagnostics, Research Institute for Production Development, 15 Simogamo-Morimoto-cho, Sakyo-Ku, Kyoto 606-0805, Japan
Shigehisa Takai
- Department of Environmental Health Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Kazuhito Watabe
- Department of Environmental Health Sciences, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan
Yukikazu Kaino
- Department of Pediatrics, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan
Kaichi Kida
- Department of Pediatrics, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan

Received 2 September 2000; received in revised form 18 January 2001; accepted 28 February 2001.

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 β-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)-β, which induces IgA-producing B-cells, in serum. Although the cytokine TGF-β 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.

Keywords: Bovine serum albumin, Lactoglobulin, Ovalbumin, Antibodies, Type 1 diabetes mellitus

Abbreviations: BLG, β-lactoglobulin, BSA, bovine serum albumin, ELISA, enzyme-linked immunosorbent assay, Ig, immunoglobulin, IL, interleukin, OVA, ovalbumin, TGF, transforming growth factor