Inverse relationship between organ-specific autoantibodies and systemic immune mediators in type 1 diabetes and type 2 diabetes: Action LADA 11

Nanette C. Schloot, Minh N. Pham, Mohammed I. Hawa, Paolo Pozzilli, Werner Scherbaum, Matthias Schott, Hubert Kolb, Steven Hunter, Guntram Schernthaner, Charles Thivolet, Jochen Seissler, Richard David Leslie, David Leslie, Huriya Beyan, Stavroula A. Paschou, Rhys Williams, Sinead Brophy, H. Davies, Henning BeckNielsen, Knud YderstraedeDavid Hadden, Raffaella Buzzetti, Jaako Tuomilehto, Cinzia Sarti, Alberto De Leiva, Eulalia Brugues, Didac Mauricio

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20 Citations (Scopus)

Abstract

© 2016 by the American Diabetes Association. OBJECTIVE: We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: From the European Action LADA (latent autoimmune diabetes in adults) cohort, patients with adult-onset type 1 diabetes (n = 80, of whom 50 had LADA and 30 had classic type 1 diabetes) and type 2 diabetes (n = 626) were analyzed for DAAs (GAD antibody [GADA], IA-2 antigen, islet cell antibody, and zinc transporter T8), non-DAAs (transglutaminase, thyroid peroxide autoantibodies, parietal cell antibodies), and 10 immune mediator concentrations (measured by LUMINEX). RESULTS: Type 1 diabetes patients (whether having classic type 1 diabetes or LADA), apart from their clinical phenotype, could not be distinguished by either autoantibodies (both DAAs and non-DAAs) or immune mediators. In type 1 diabetes, most immune mediators (9 of 10) were negatively correlated with DAA titers. Type 2 diabetes patients, who by definition were without DAAs, had fewer non-DAAs (P < 0.0005), but had higher levels of proinflammatory immune mediators, especially compared with patients with type 1 diabetes who had high GADA titers (interleukin [IL]-6 [P < 0.001], soluble E-selectin [P < 0.01], and IL-1 receptor antagonist [P = 0.052], for trend). CONCLUSIONS: Patients with type 1 diabetes had more DAAs and non-DAAs than did those with type 2 diabetes, whereas the frequency and nature of these autoantibodies was broadly similar in classic type 1 diabetes and LADA. Systemic immune mediator levels, in the main, were negatively correlated with DAA titers, and, for some, were higher in patients with type 2 diabetes, especially when compared with patients who had high GADA titers. Differences in the clinical classification of diabetes are associated with graded differences in adaptive and innate immune reactivity.
Original languageEnglish
Pages (from-to)1932-1939
JournalDiabetes Care
Volume39
Issue number11
DOIs
Publication statusPublished - 1 Nov 2016

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