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Identification of tyrosine posphatase 2(256-760) construct as a new, sensitive marker for the detection of islet autoimmunity in type 2 diabetic patients (NIRAD Study 2)

  1. Claudio Tiberti (claudio.tiberti{at}uniroma1.it)1,
  2. Carla Giordano2,
  3. Mattia Locatelli3,
  4. Emanuele Bosi4,
  5. Gian Franco Bottazzo3,
  6. Raffaella Buzzetti1,
  7. Domenico Cucinotta5,
  8. Aldo Galluzzo2,
  9. Alberto Falorni6 and
  10. Francesco Dotta7
  1. 1Department of Clinical Sciences, University of Rome “La Sapienza”, Rome, Italy
  2. 2Department of Endocrinology, University of Palermo, Italy
  3. 3Scientific Institute, Bambino Gesù Hospital, Rome, Italy
  4. 4General Medicine, Diabetes & Endocrinology, San Raffaele Scientific Institute and Vita Salute University, Milan, Italy
  5. 5Department of Internal Medicine, University of Messina, Messina, Italy
  6. 6Department of Internal Medicine, University of Perugia, Perugia, Italy
  7. 7Department of Internal Medicine, Endocrine and Metabolic Sciences and Biochemistry, University of Siena, Siena, Italy

    Abstract

    Objective: The presence of autoantibodies to islet antigens GAD and/or IA-2 in type 2 diabetic patients identifies those subjects (LADA) at high risk to develop insulin dependency. 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: Patients: 177 LADA and 978 type 2 diabetic patients with different disease duration, collected in a nationwide italian survey (NIRAD Study) aimed at assessing prevalence and characteristics of autoimmune diabetes in type 2 diabetic patients; 106 newly-diagnosed type 1 diabetic patients (53 children, 53 adults) Method: analysis by radioimmunoassay of humoral immunoreactivity to 7 IA-2 constructs [IA-2PTP(687-979),IA-2(761-964),IA-2(256-760),IA-2JM(601-630),IA-2IC(605-979),IA-2BDC(256-556:630-979),IA-2FL(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, identifying IA-2 autoantibodies in almost 30% of GADA positive LADA and in 3.4% of GADA negative type 2 diabetic patients. LADA IA-2(256-760)A positivity was associated to an increased frequency of autoimmune diabetes HLA susceptible genotypes and to a higher risk for developing thyroid autoimmunity compared to autoantibody negative type 2 diabetic patients. At disease diagnosis, adult-onset type 1 diabetic and LADA patients showed a lower IA-2 C-terminal immunoreactivity compared to childhood-onset type 1 diabetic patients

    Conclusions: IA-2 immunoreactivity in LADA patients was so far underestimated and IA-2(256-760) autoantibody detection may represent a novel diagnostic tool for the identification of islet autoimmunity in these patients.

    Footnotes

      • Received June 28, 2007.
      • Accepted January 23, 2008.

    This Article

    1. Published online before print March 10, 2008, doi: 10.2337/db07-0874 Diabetes March 10, 2008
    1. » Abstract
    2. Full Text (PDF)
    3. Online-Only Appendix
    4. All Versions of this Article:
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