Antibodies to Bovine Serum Albumin in Japanese IDDM Children; No Association with GAD Antibodies and HLA Risk Genotypes

The implications of Bovine serum albumin (BSA) in cow's milk proteins in the pathogenesis of insulin-dependent diabetes mellitus (IDDM) have been suggested, but is controversial even in Caucasians, and have been addressed in limited studies in other ethnic groups. We studied the prevalence of antibodies to BSA (BSAAb) in sera from Japanese children with IDDM, and compared it to those in children with other diseases including non insulin-dependent diabetes mellitus (NIDDM), autoimmune thyroid disease (AITD) and congenital hypothyroidism (cretinism) by using enzymelinked immunosorbent assay (ELISA). Significant levels of BSAAb were detected in sera from non-diabetic normal children, and higher levels in younger (1-3 years of age) than in older children (4-9 years of age). Only 2 of 20 (10%) recent-onset IDDM patients of age ≥ 4 years were assessed to have high titers of BSAAb compared to normal controls, and none of 8 sera from those of age <4 years were positive for BSAAb. No significant difference in the incidence of BSAAb was found among the various groups of children examined in both age groups. It appeared that BSAAb in IDDM patients bound to different sites on BSA from ABBOS (a 17-amino acid peptide, position 152 to 168 of BSA), based on the result that no significant blocking of BSAAb by the addition of ABBOS was detected by inhibition assay. Antibodies to glutamic acid decarboxylase (GADAb) in sera and human leukocyte antigen (HLA) -DR, -DQ genotypes of 28 recent-onset IDDM patients were examined. In addition, there was no significant difference between GADAb-positive and -negative IDDM patients in the titers of BSAAb. No association of BSAAb with HLA genotypes such as HLA-DR9-DQ9 and DR4-DQ4 was found in recent-onset IDDM patients. Collectively, BSAAb was not associated with IDDM in Japanese children.