title: GADA titer-related risk for organ-specific autoimmunity in LADA subjects subdivided according to gender (NIRAD study 6).
abstract: BACKGROUND
  Latent autoimmune diabetes in adults (LADA) includes a heterogeneous population wherein, based on glutamic acid decarboxylase antibody (GADA) titer, different subgroups of subjects can be identified.
  
  
  OBJECTIVE
  The aim of the present study was to evaluate GADA titer-related risk for β-cell and other organ-specific autoimmunity in LADA subjects.
  
  
  METHODS
  Adult-onset autoimmune diabetes subjects (n=236) and type 2 diabetes (T2DM) subjects (n=450) were characterized for protein tyrosine phosphatase (IA-2IC and IA-2(256-760)), zinc transporter 8 (ZnT8), thyroid peroxidase, (TPO), steroid 21-hydroxylase (21-OH), tissue transglutaminase (tTG), and antiparietal cell (APC) antibodies.
  
  
  RESULTS
  High GADA titer compared to low GADA titer showed a significantly higher prevalence of IA-2IC, IA-2(256-760), ZnT8, TPO, and APC antibodies (P≤0.04 for all comparison). 21-OH antibodies were detected in 3.4% of high GADA titer. A significant decreasing trend was observed from high GADA to low GADA and to T2DM subjects for IA-2(256-760), ZnT8, TPO, tTG, and APC antibodies (P for trend≤0.001). TPO was the only antibody showing a different prevalence between gender; low GADA titer and T2DM female patients had a higher frequency of TPO antibody compared to males (P=0.0004 and P=0.0006, respectively), where the presence of high GADA titer conferred an odds ratio of 8.6 for TPO compared to low GADA titer. After subdividing high and low GADA titer subjects according to the number of antibodies, we observed that 73.3% of high GADA titer subjects were positive for at least one or more antibodies, compared to 38.3% of low GADA titer (P<0.0001).
  
  
  CONCLUSIONS
  In LADA subjects, high GADA titer was associated with a profile of more severe autoimmunity and, in male gender, specifically predisposed to thyroid autoimmunity. A regular screening for other antibodies is recommended in LADA patients according to GADA titer and gender.
authors.affiliation: Department of Internal Medicine and Medical Specialties, Sapienza University, Viale del Policlinico 155, 00161 Rome, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Zampetti
authors.forename: Marco
authors.initials: M
authors.lastname: Capizzi
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Spoletini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campagna
authors.forename: Gaetano
authors.initials: G
authors.lastname: Leto
authors.forename: Laura
authors.initials: L
authors.lastname: Cipolloni
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
mesh_terms: D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D050417:Insulin-Secreting Cells / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D016036:Seroepidemiologic Studies; D017678:Sex Distribution; D013961:Thyroid Gland / Q000276:immunology
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2