DIFFERENTIAL IMMUNOGENETIC DETERMINANTS OF POLYCLONAL INSULIN AUTOIMMUNE SYNDROME (HIRATAS DISEASE) AND MONOCLONAL INSULIN AUTOIMMUNE SYNDROME

The insulin autoimmune syndrome (IAS), or Hirata's disease, is charact erized by the combination of fasting hypoglycemia, high concentration of total serum immunoreactive insulin, and presence of autoantibodies to native human insulin in serum, Autoantibody production is classifie d as monoclonal or polyclonal, with the majority of IAS cases classifi ed as polyclonal, Previously, we observed a striking association betwe en the human leukocyte antigen (HLA) class II alleles DRB1040/DQAI*03 01/DQB10302 and Japanese IAS patients with polyclonal insulin autoant ibodies (IAAs) and T-cell recognition of human insulin in the context of DRB10406 molecules. Because of such a strong HLA association in IA S, we performed intra- and interethnic studies on IAS-associated DRB1 alleles and searched for the critical amino acid residue(s) for IAS pa thogenesis. Glutamate at position 74 in the HLA-DR4 beta 1-chain was p resumed to be essential to the production of polyclonal IAA in LAS, wh ereas alanine at the same position of the HLA-DR beta 1-chain might be important in the production of monoclonal IAA.