Inverse Relationship Between Organ-Specific Autoantibodies and Systemic Immune Mediators in Type 1 Diabetes and Type 2 Diabetes: Action LADA 11
Por:
Schloot, NC, Pham, MN, Hawa, MI, Pozzilli, P, Scherbaum, WA, Schott, M, Kolb, H, Hunter, S, Schernthaner, G, Thivolet, C, Seissler, L, Leslie, RD, Mauricio, D.
Publicada:
1 nov 2016
Resumen:
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.
Filiaciones:
Schloot, NC:
Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany
Pham, MN:
Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany
Novo Nordisk Res Ctr, Seattle, WA USA
Hawa, MI:
Queen Mary Univ London, Blizard Inst, London, England
Pozzilli, P:
Univ Campus Biomed, Dept Endocrinol & Diabet, Rome, Italy
Scherbaum, WA:
Univ Dusseldorf, Fac Med, Dusseldorf, Germany
Schott, M:
Univ Dusseldorf, Fac Med, Div Specif Endocrinol, Dusseldorf, Germany
Kolb, H:
Verbund Katholischer Kliniken Dusseldorf, West German Ctr Diabet & Hlth, Dusseldorf, Germany
Hunter, S:
Royal Victoria Hosp, Reg Ctr Endocrinol & Diabet, Belfast, Antrim, Ireland
Schernthaner, G:
Rudolfstiftung Hosp, Dept Med, Vienna, Austria
Thivolet, C:
Hosp Civils Lyon, Lyon Sud Hosp, Dept Endocrinol & Diabet, Pierre Benite, France
Univ Lyon 1, Lyon, France
Seissler, L:
Univ Munich, Ctr Diabet, Med Klin & Poliklin 4, Munich, Germany
Leslie, RD:
Queen Mary Univ London, Blizard Inst, London, England
Mauricio, D.:
Hospital de Sant Pau, Barcelona, Spain
Bronze
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