AUTOANTIBODIES AGAINST A NOVEL 51-KDA ISLET ANTIGEN AND GLUTAMATE-DECARBOXYLASE ISOFORMS IN AUTOIMMUNE POLYENDOCRINE SYNDROME TYPE-I

Beta-cell function and islet cell antibodies were studied in six patie nts with autoimmune polyendocrine syndrome type I. All suffered from m ucocutaneous candidiasis, five had adrenocortical insufficiency and th ree hypoparathyroidism. All sera contained high titres of antibodies s taining islets of Langerhans. Reactivity against glutamate decarboxyla se, predominantly the 65 kDa isoform, was detected by immunoprecipitat ions and Western blots in five of the six sera, and all six sera immun oprecipitated a 51 kDa antigen from [S-35] methionine labelled rat isl et cell lysates. No reactivity against this latter antigen was found i n sera of patients with Type 1 (insulin-dependent) diabetes mellitus ( n = 9), Graves' disease (n = 5), autoimmune gastritis (n = 4), idiopat hic Addison's disease (n = 7), or stiff-man syndrome (n = 2). The 51 k Da antigen was also detected by Western blots using homogenates of rat islets and autoimmune polyendocrine syndrome type I patient sera, whe reas no such reactivity was found with homogenates of testes, adrenals , small intestine, spleen, exocrine pancreas or brain. Moreover, the 5 1 kDa antigen was present in the rat insulinoma cell line RINm 5F but not in the SV-40 transformed, monkey kidney cell line COS, when examin ed by immunoprecipitations of [S-35]-methionine labelled cell lysates and by Western blots. None of the patients with autoimmune polyendocri ne syndrome type I had symptoms of diabetes and their insulin response s to glucose challenge were normal. The data illustrate that patients with autoimmune polyendocrine syndrome type I present an autoimmune re sponse against islets of Langerhans, which is apparently different fro m that associated with classic Type 1 diabetes. As most of the autoant igens in many autoimmune diseases are enzymes involved in important fu nctions in the affected organs, it is possible that the anti-51 kDa an tibodies are directed against a protein with important functional acti vity in the islet.