title: Inverse Relationship Between Organ-Specific Autoantibodies and Systemic Immune Mediators in Type 1 Diabetes and Type 2 Diabetes: Action LADA 11.
abstract: We related organ-specific autoantibodies, including diabetes-associated autoantibodies (DAAs) and non-DAAs to systemic cytokines/chemokines in type 1 and type 2 diabetes.
  
  
  
  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).
  
  
  
  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).
  
  
  
  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.
authors: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany nanette.schloot@web.de.
authors: Nanette C
authors: NC
authors: Schloot
authors: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich-Heine University, Düsseldorf, Germany.|Novo Nordisk Research Center, Seattle, WA.
authors: Minh N
authors: MN
authors: Pham
authors: Blizard Institute, Queen Mary University of London, London, U.K.
authors: Mohammed I
authors: MI
authors: Hawa
authors: Department of Endocrinology and Diabetes, University Campus Bio-Medico, Rome, Italy.
authors: Paolo
authors: P
authors: Pozzilli
authors: University of Düsseldorf, Medical Faculty, Düsseldorf, Germany.
authors: Werner A
authors: WA
authors: Scherbaum
authors: University of Düsseldorf, Medical Faculty, Division for Specific Endocrinology, Düsseldorf, Germany.
authors: Matthias
authors: M
authors: Schott
authors: West-German Centre of Diabetes and Health, Verbund Katholischer Kliniken Düsseldorf, Düsseldorf, Germany.
authors: Hubert
authors: H
authors: Kolb
authors: Regional Centre for Endocrinology and Diabetes, Royal Victoria Hospital, Belfast, Ireland.
authors: Steven
authors: S
authors: Hunter
authors: Department of Medicine, Rudolfstiftung Hospital, Vienna, Austria.
authors: Guntram
authors: G
authors: Schernthaner
authors: Department of Endocrinology and Diabetes, Lyon-Sud Hospital, Hospices Civils de Lyon, Pierre Benite, France; Université Claude-Bernard Lyon, Lyon, France.
authors: Charles
authors: C
authors: Thivolet
authors: Medizinische Klinik und Poliklinik IV, Diabetes Center, Ludwig-Maximillians-University, Munich, Germany.
authors: Jochen
authors: J
authors: Seissler
authors: Blizard Institute, Queen Mary University of London, London, U.K.
authors: Richard David
authors: RD
authors: Leslie
mesh_terms: D000328:Adult; D000368:Aged; D001323:Autoantibodies / Q000276:immunology*; D027682:Cation Transport Proteins / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology* / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007453:Iodide Peroxidase / Q000276:immunology; D000071698:Latent Autoimmune Diabetes in Adults / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010295:Parietal Cells, Gastric / Q000276:immunology; D010641:Phenotype; D011503:Transglutaminases / Q000276:immunology; D000075703:Zinc Transporter 8
chemical_list: D001323:Autoantibodies; D027682:Cation Transport Proteins; D019040:E-Selectin; C096322:ICA512 autoantibody; C507763:IL1RN protein, human; C508600:IL6 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D015850:Interleukin-6; C492522:SLC30A8 protein, human; D000075703:Zinc Transporter 8; C024211:islet cell antibody; D007453:Iodide Peroxidase; D011503:Transglutaminases; D005968:Glutamate Decarboxylase