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Autoantibodies and Human Leucocyte Antigen Class II in First-Degree Family Members of Mexican-American Type 1 Diabetic Patients

Division of Endocrinology and Diabetes, LAC-USC Medical Center (T.A.B.), Keck USC School of Medicine (A.Z., S.J.S.), Los Angeles, California 90033; Division of Medical Genetics, Cedars-Sinai Research Institute and UCLA (L.J.R., J.I.R.), Los Angeles, California 90048; Division of Endocrinology and Metabolism, Children’s Hospital of Los Angeles (G.C.), Los Angeles, California 90027; California Children’s Hospital of Oakland Research Institute (J.P.K., C.W.), Oakland, California 94611; Division of Endocrinology, Metabolism, and Nutrition, University of Washington, VA Medical Center (J.P.), Seattle, Washington 94609; H. Lee Moffitt Cancer Center and Research Institute (J.P.K.), University of South Florida, Tampa, Florida 33612; and Weill Medical College at Cornell University (N.K.M.), New York, New York 10021

Address all correspondence and requests for reprints to: Adina Zeidler, M.D., Division of Endocrinology and Diabetes 1200 North State Street, Los Angeles, California 90033. E-mail:azeidler{at}hsc.usc.edu

Abstract

As part of a genetic study of type 1 diabetes in Mexican-Americans, 360 first-degree relatives of 108 type 1 diabetic probands were studied. Islet cell antibody (ICA), insulin autoantibody, glutamic acid decarboxylase (GAD₆₅), and protein tyrosine phosphatase autoantibodies were measured and human leucocyte antigen (HLA) class II alleles DRB1 and DQB1 genotyping was performed. ICA was positive in 37% of the probands and 5.8% of the relatives. A subgroup of 26 probands (12 ICA+, 14 ICA-) was tested for GAD₆₅ and was found positive. 4/14 ICA+ first-degree relatives were GAD₆₅ positive. Four relatives, positive for two antibodies, subsequently developed type 1 diabetes. Life-Table analysis of first-degree relatives with autoantibodies indicated an 80% disease-free survival at 3.5 yr. HLA-DRB1 was found to be associated with the presence of ICA in both probands and relatives, whereas HLA-DPB1 was associated with autoantibody in relatives of type 1 diabetic probands.