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Autoantibodies to a 38-kDa Glycosylated Islet Cell Membrane–Associated Antigen in (Pre)type 1 Diabetes

Association with IA-2 and islet cell autoantibodies

¹ Diabetes Research Center, Vrije Universiteit Brussel, Brussels, Belgium
² Department of Diabetes, Endocrinology and Internal Medicine, Guy’s, King’s College and St. Thomas’ School of Medicine, London, U.K.
³ Department of Pediatrics, Sophia’s Children’s Hospital, Erasmus University Medical Center, Rotterdam, the Netherlands
⁴ Department of Endocrinology, Hôpital de Jolimont, Haine-Saint-Paul
⁵ Department of Endocrinology, O.L.V. Hospitaal, Kortrijk
⁶ Brussels, Belgium

OBJECTIVE—To study the association of autoantibodies against a 38-kDa glycated islet cell membrane–associated (GLIMA) protein with (pre)type 1 diabetes, patient characteristics, and other immune and genetic markers of the disease and to evaluate the possible added value of GLIMA antibody determinations for disease prediction and classification.

RESEARCH DESIGN AND METHODS—Recent-onset type 1 diabetic patients (n = 100), prediabetic siblings (n = 23), and nondiabetic control subjects (n = 100) were consecutively recruited by the Belgian Diabetes Registry. GLIMA antibodies were determined by immunoprecipitation of radiolabeled islet cell proteins; islet cell antibodies (ICAs) were determined by indirect immunofluorescence; and insulin autoantibodies (IAAs), insulinoma-associated protein-2 antibodies (IA-2As), and GAD antibodies (GADAs) were determined by radioligand assays.

RESULTS— GLIMA antibodies were detected in 38% of type 1 diabetic patients and 35% of prediabetic siblings (during follow-up) vs. 0% in control subjects (P < 0.001). Their prevalence was lower than that of other antibodies and was significantly associated with high levels of IA-2A and ICA (P < 0.0001). In (pre)diabetes, GLIMA antibodies could only be demonstrated in sera positive for 1 other autoantibody.

CONCLUSIONS— GLIMA antibodies are strongly associated with type 1 diabetes and antibody markers of rapid progression to clinical onset but have a lower diagnostic sensitivity for the disease than IAA, ICA, IA-2A, or GADA. In its present form, the GLIMA antibody assay does not provide much additional information for prediction or classification of diabetes, compared with that obtained from the measurement of IA-2As alone or in combination with IAAs, ICAs, and GADAs.

Abbreviations: GADA, GAD antibody • GLIMA, glycated islet cell membrane–associated protein • IA-2, insulinoma-associated protein-2 • IA-2A, IA-2 antibody • IAA, insulin autoantibody • ICA, islet cell antibody • JDF U, Juvenile Diabetes Foundation units • TX-114, Triton X-114

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