ISLET AUTOANTIBODY MARKERS IN IDDM - RISK ASSESSMENT STRATEGIES YIELDING HIGH-SENSITIVITY

Identification of islet autoantigens offers the possibility that antib ody tests other than islet cell antibodies may be used for assessing r isk of insulin-dependent diabetes mellitus (IDDM). The aim of this stu dy was to determine the combination of islet autoantibody markers that could identify most future cases of IDDM. Islet cell antibodies, anti bodies to glutamic acid decarboxylase (GAD)(65), 37,000/40,000 M(r) is let tryptic fragments, carboxypeptidase-H, and islet cell autoantigen (ICA)69 were measured in sera from 100 newly-diagnosed IDDM patients, 27 individuals prior to onset of IDDM, and 83 control subjects. Islet cell antibodies were detected in 88 % of IDDM patients and 81 % with p re-IDDM, GAD(65) antibodies in 70 % of IDDM patients and 89 % with pre -IDDM, and antibodies to 37,000/40,000 M(r) islet tryptic fragments in 54 % of IDDM patients and in 48 % with pre-IDDM. The latter were foun d only in conjunction with islet cell antibodies and were more frequen t in young onset cases. All 20 IDDM patients and the 3 pre-IDDM subjec ts who had islet cell anti-bodies without GAD(65) antibodies had antib odies to 37,000/40,000 M(r) islet tryptic fragments, and all but one h ad disease onset before age 15 years. No sera strongly immunoprecipita ted in vitro translated ICA69 or carboxypeptidase-H; 4 % of patients h ad anti-ICA69 and 11 % anti-carboxypeptidase-H levels above those of t he control subjects. The findings suggest that none of the single anti body specificities are as sensitive as islet cell antibodies, but that a combination of GAD(65) antibodies and antibodies to 37,000/40,000 M (r) islet tryptic fragments has the potential to identify more than 90 % of future cases of IDDM. Such a strategy could eventually replace i slet cell antibodies in population screening for IDDM risk assessment.