title: Identification of tyrosine phosphatase 2(256-760) construct as a new, sensitive marker for the detection of islet autoimmunity in type 2 diabetic patients: the non-insulin requiring autoimmune diabetes (NIRAD) study 2.
abstract: OBJECTIVE
  The presence of autoantibodies to islet antigens GAD and/or tyrosine phosphatase 2 (IA-2) in type 2 diabetic patients (latent autoimmune diabetes in adults [LADA]) identifies subjects at high risk to develop insulin dependency. The aim of this study was to dissect humoral anti-IA-2 immune response in Caucasian LADA patients, identifying the most sensitive construct to evaluate IA-2 immunoreactivity and comparing LADA IA-2 epitope specificities to those found in type 1 diabetes.
  
  
  METHODS
  We analyzed 177 LADA and 978 type 2 diabetic patients with different disease duration, collected in a nationwide Italian survey, the Non-Insulin Requiring Autoimmune Diabetes (NIRAD) study aimed at assessing prevalence and characteristics of autoimmune diabetes in type 2 diabetic patients and 106 newly diagnosed type 1 diabetic patients (53 children, 53 adults). By radioimmunoassay, we analyzed humoral immunoreactivity to seven IA-2 constructs: IA-2(PTP (687-979)), IA-2((761-964)), IA-2((256-760)), IA-2(JM (601-630)), IA-2(IC (605-979)), IA-2(BDC (256-556:630-979)), and IA-2(FL (1-979)).
  
  
  RESULTS
  IA-2((256-760)) fragment was identified as the marker with the highest sensitivity for detection of humoral IA-2 immunoreactivity in LADA patients, identifying IA-2 autoantibodies in approximately 30% of GAD antibody (GADA)-positive LADA patients and in 3.4% of GADA-negative type 2 diabetic patients. LADA IA-2((256-760))A positivity was associated with an increased frequency of autoimmune diabetes HLA-susceptible genotypes and with a higher risk for developing thyroid autoimmunity compared with autoantibody-negative type 2 diabetic patients. At disease diagnosis, adult-onset type 1 diabetic and LADA patients showed a lower IA-2 COOH-terminal immunoreactivity compared with childhood-onset type 1 diabetic patients.
  
  
  CONCLUSIONS
  IA-2 immunoreactivity in LADA patients has thus far been underestimated, and IA-2((256-760)) autoantibody detection may represent a novel diagnostic tool for the identification of islet autoimmunity in these patients.
authors.affiliation: Department of Clinical Sciences, University of Rome La Sapienza, Rome, Italy. claudio.tiberti@uniroma1.it
authors.forename: Claudio
authors.initials: C
authors.lastname: Tiberti
authors.forename: Carla
authors.initials: C
authors.lastname: Giordano
authors.forename: Mattia
authors.initials: M
authors.lastname: Locatelli
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bosi
authors.forename: Gian Franco
authors.initials: GF
authors.lastname: Bottazzo
authors.forename: Raffaella
authors.initials: R
authors.lastname: Buzzetti
authors.forename: Domenico
authors.initials: D
authors.lastname: Cucinotta
authors.forename: Aldo
authors.initials: A
authors.lastname: Galluzzo
authors.forename: Alberto
authors.initials: A
authors.lastname: Falorni
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
mesh_terms: D000328:Adult; D001323:Autoantibodies / Q000097:blood*; D015551:Autoimmunity; D015415:Biomarkers / Q000032:analysis; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology*; D006306:Health Surveys; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D007558:Italy; D010446:Peptide Fragments / Q000032:analysis / Q000737:chemistry*; D017027:Protein Tyrosine Phosphatases / Q000737:chemistry*
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D010446:Peptide Fragments; D017027:Protein Tyrosine Phosphatases