COMBINED ANALYSIS OF GAD65 AND ICA512(IA-2) AUTOANTIBODIES IN ORGAN AND NON-ORGAN-SPECIFIC AUTOIMMUNE-DISEASES CONFERS HIGH SPECIFICITY FORINSULIN-DEPENDENT DIABETES-MELLITUS

There is evidence that insulin-dependent diabetes mellitus (IDDM) may develop in association with other non-beta-cell-specific autoimmune di seases. We aimed to assess whether autoantibodies to the islet cell an tigens glutamic acid decarboxylase (M-r 65,000 isoform) (GAD65) and IC A512(IA-2), present alone or in combination, are limited to IDDM or al so occur in other organ- or non-organ-specific autoimmune disorders. W e determined the frequency of these autoantibodies by radioimmunoassay in 199 sera from patients with autoimmune thyroid diseases (AITD), rh eumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primar y biliary cirrhosis (PBC), and compared the results with those from 50 7 newly diagnosed patients with IDDM and 280 healthy controls. ICA512( IA-2) autoantibodies were detected exclusively in AITD with concurrent IDDM, but not in other autoimmune diseases without IDDM, whereas GAD6 5 autoantibodies exceeded the limit of normal in 67.7% (21 of 31) of p atients with AITD who also had IDDM and in 5.5% (three of 55) of patie nts with PBC. The frequency of either GAD65 and/or ICA512(IA-2) autoan tibodies was significantly higher in patients with AITD who also had I DDM (27 of 31, 87.2%) than in those with AITD alone (one of 53, 1.9%; P<10(-6)), but was not significantly different from those patients wit h newly diagnosed IDDM (418 of 507, 82.4%). Neither patients with orga n-or non-organ-specific autoimmune diseases without IDDM nor healthy c ontrols had autoantibodies against both GAD65 and ICA512(IA-2). Despit e the fact that one of the two autoantibodies was occasionally detecte d in patients with non-beta-cell-specific autoimmune diseases without IDDM, combined determination of GAD65 and ICA512(IA-2) autoantibodies specifically identified IDDM in the majority of patients with AITD. In conclusion, because of the strong association of IDDM with AITD, test ing for multiple islet autoantibodies could be useful as a predictive marker for risk of progression to IDDM onset amongst patients with aut oimmune thyroid disorders. (C) 1998 Academic Press Limited.