© Freund Publishing House Ltd., London Journal of Pediatric Endocrinology & Metabolism, 15, 831-840 (2002) Diabetes Mellitus-Related Autoantibodies in Childhood Autoimmune Hepatitis Maria E.R. da Silva 1 , Gilda Porta 2 , Ana C. Golberg 3 , Paulo L. Bittencourt 2 , Rosa T. Fukui 1 , Marcia R.S. Correia 1 , Irene K. Miura 2 , Renata S. Pugliese 2 , Vera L. Baggio 2 , Eduardo L.R. Can<^ado 3 , Jorge Kalil 1 , Rosa F. Santos 1 , Dalva M. Rochal 1 , Bernardo L. Wajchenberg 1 , Mileni J.M. Ursich 1 and Arlan L. Rosenbloom 4 'Laboratory of Medical Investigation (LIM 18), 2 Children's Institute and 3 Laboratory of Transplantation Immunology, Sao Paulo Medical School, Säo Paulo, Brazil and 4 Department of Pediatrics, University of Florida College of Medicine, Gainesville, FL, USA ABSTRACT Objective: To determine the frequency and significance of diabetes mellitus (DM)-related autoantibodies in children with autoimmune hepatitis (AIH). Research design and methods·. Anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), and anti-glutamic acid decarboxylase (GAD65) antibodies were assessed in 28 children (25 female) with AIH before and after 3-9 years of therapy with azathioprine and prednisone. Results: There was biochemical and clinical remission of AIH activity in 76% of the children after 1 year of immunosuppressive therapy. Positive ICA and IAA were found in 60.7% and 18.5% of the patients, decreasing to 38.5% and 12% after 3-9 years of therapy. Anti-GAD autoantibodies were present in only one patient who had Graves' disease, high ICA titer, and developed type 1 DM after 3 years. After 3-9 years of follow up, all had normal fasting glycemia, glycosylated hemoglobin (HbAi c ), and, with a single exception, normal responses to oral glucose tolerance testing. No increase in the frequencies of HLA antigens was observed in ICA- and IAA-positive patients compared to antibody-negative patients or a control popula- tion. The majority of the patients with HLA- DRB1*03 or DRB1*04, however, were positive Reprint address: Maria Elizabeth Rossi da Silva, M.D., Ph.D. Rua Joäo Moura 627 conj 72 Säo Paulo, SP Brazil 05412-911 for ICA (7/10), and three of them had IAA. The frequency of high risk HLA DQB 1*0302 or DQB1*02 alleles was low and similar to control frequencies, indicating low-risk for DM despite the presence of DM-related autoimmunity markers. Conclusions·. AIH in childhood is associated with high frequency of ICA and IAA, with less than expected rates of progression to DM. Immunosuppression reduced ICA and IAA frequency and titers. KEY WORDS diabetes mellitus-related autoantibodies, auto- immune hepatitis, anti-islet cell antibodies (ICA), insulin autoantibodies (IAA), anti-glutamic acid decarboxylase (GAD65) antibodies, azathioprine, prednisone, immunosuppression, Graves' disease, HLA antigens INTRODUCTION Autoimmune hepatitis (AIH) is a form of chronic active hepatitis of unknown etiology, characterized by circulating non-organ and liver- specific autoantibodies and hypergammaglobulin- emia, responsive to immunosuppressive therapy 1 " 3 . The disease affects both children and adults, with marked female predominance. AIH may be classified into two distinct subgroups according to the circulating autoantibodies found. Patients with type 1 (classical) AIH usually have anti-smooth muscle (anti-actin) antibodies (SMA), or anti- nuclear antibodies (ANA). Type 2 AIH is defined VOLUME 15, NO. 6, 2002 831 Brought to you by | University of California - San Francisco Authenticated Download Date | 2/20/15 5:51 PM