title: Neuronal T-cell autoreactivity is amplified in overweight children with new-onset insulin-requiring diabetes.
abstract: OBJECTIVE
  Disease-associated T-cell autoreactivities are seen in most type 1 diabetic patients and are thought to emerge before islet autoantibodies, but host factors that impact autoimmune elements remain uncertain. We assessed if adiposity and measures of insulin sensitivity impact T- and B-cell autoimmunity in children with insulin-requiring diabetes.
  
  
  METHODS
  Insulin-requiring children and adolescents diagnosed between January 2004 and June 2008 were studied (n = 261): age 9.7 ± 4 years, 92% white, and 60% male. T-cell responses to 10 diabetes-associated antigens, β-cell autoantibodies (GADA, IA-2A, IAA, and ICA), BMI z score (BMIz), and waist percentile were measured at onset and 3 months later.
  
  
  RESULTS
  All but one subject had either T- or B-cell autoimmunity. Diabetes-associated T-cell autoreactivities were found in 92% of subjects. Higher amplitude T-cell autoreactivities to neuronal diabetes-associated autoantigens were seen in those with the highest BMIz quintile, BMI ≥85th percentile (P < 0.05), and waist circumference ≥85th percentile (P < 0.05). There were no relationships between the number of T-cell reactivities or T-cell diversity with adiposity measures or autoantibody number or type. Patients with positive T-cell reactivities but without autoantibodies had the highest BMIz (P = 0.006).
  
  
  CONCLUSIONS
  Our observations link obesity and diabetes-related autoimmunity, suggesting an amplification of neuronal T-cell autoimmunity associated with adiposity and/or insulin resistance, with obesity-related inflammation possibly enhancing islet autoimmunity.
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Buryk
authors.affiliation: Neurosciences and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: H-Michael
authors.initials: HM
authors.lastname: Dosch
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Libman
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Arena
authors.affiliation: Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.
authors.forename: Yihe
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Neurosciences and Mental Health Program, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: Roy K
authors.initials: RK
authors.lastname: Cheung
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA.
authors.forename: Massimo
authors.initials: M
authors.lastname: Trucco
authors.affiliation: Department of Immunology, University of Michigan, Ann Arbor, MI.
authors.forename: Massimo
authors.initials: M
authors.lastname: Pietropaolo
authors.affiliation: Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA dorothy.becker@chp.edu.
authors.forename: Dorothy J
authors.initials: DJ
authors.lastname: Becker
mesh_terms: D000293:Adolescent; D000483:Alleles; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015992:Body Mass Index; D002096:C-Peptide / Q000097:blood; D049109:Cell Proliferation; D002648:Child; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D050417:Insulin-Secreting Cells / Q000276:immunology; D007515:Islets of Langerhans / Q000276:immunology / Q000378:metabolism; D008297:Male; D063766:Pediatric Obesity / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D055105:Waist Circumference
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D002096:C-Peptide; D007328:Insulin