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. RESEARCH DESIGN AND 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.

journal_name

Diabetes

journal_title

Diabetes

authors

Tiberti C,Giordano C,Locatelli M,Bosi E,Bottazzo GF,Buzzetti R,Cucinotta D,Galluzzo A,Falorni A,Dotta F

doi

10.2337/db07-0874

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

1276-83

issue

5

eissn

0012-1797

issn

1939-327X

pii

db07-0874

journal_volume

57

pub_type

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