IA-2, a transmembrane protein of the protein tyrosine phosphatase family, is a major autoantigen in insulin-dependent diabetes mellitus

作者: M. S. Lan , C. Wasserfall , N. K. Maclaren , A. L. Notkins

DOI: 10.1073/PNAS.93.13.6367

关键词:

摘要: IA-2 is a 105,847 Da transmembrane protein that belongs to the tyrosine phosphatase family. Immunoperoxidase staining with antibody raised against showed this expressed in human pancreatic islet cells. In study, we full-length cDNA clone of rabbit reticulocyte transcription/translation system and used recombinant radiolabeled detect autoantibodies by immunoprecipitation. Coded sera (100) were tested: 50 from patients newly diagnosed insulin-dependent diabetes mellitus (IDDM) age-matched normal controls. Sixty-six percent patients, but none controls, reacted IA-2. The same diabetic tested for cells (ICA) indirect immunofluorescence glutamic acid decarboxylase (GAD65Ab) depletion ELISA 68% 52% positivity, respectively. Up 86% IDDM had and/or GAD65. Moreover, greater than 90% (14 15) ICA-positive GAD65Ab-negative Absorption experiments reactivity was greatly reduced prior incubation or GAD65 when respective present. A little over one-half (9 16) negative ICA found be positive GAD65, arguing test less sensitive tests It concluded major cell autoantigen IDDM, and, together responsible much islets. Tests detection may eventually replace population screening.

参考文章(25)
D. U. Rabin, J. M. Hicks, D. E. Goldstein, J. Oles, Heeja Yoo-Warren, S. M. Pleasic, J. A. Shapiro, P. M. M. Rae, Islet cell antigen 512 is a diabetes-specific islet autoantigen related to protein tyrosine phosphatases. Journal of Immunology. ,vol. 152, pp. 3183- 3188 ,(1994)
Matthias Schoot, Desmond Schatz, Mark Atkinson, Jeffrey Krischer, Hersh Mehta, Barbara Vold, Noel Maclaren, GAD65 Autoantibodies Increase the Predictability but not the Sensitivity of Islet Cell and Insulin Autoantibodies for Developing Insulin Dependent Diabetes Mellitus Journal of Autoimmunity. ,vol. 7, pp. 865- 872 ,(1994) , 10.1006/JAUT.1994.1070
Wei Huang, Jin Xiong She, Andrew Muir, Danuta Laskowska, Barbara Zorovich, Desmond Schatz, Noel K. Maclaren, High Risk HLA-DR/DQ Genotypes for IDD Confer Susceptibility to Autoantibodies but DQB1*0602 does not Prevent them Journal of Autoimmunity. ,vol. 7, pp. 889- 897 ,(1994) , 10.1006/JAUT.1994.1073
J. Lu, A.L. Notkins, M.S. Lan, Isolation, Sequence and Expression of a Novel Mouse-Brain cDNA, mIA-2, and Its Relatedness to Members of the Protein Tyrosine Phosphatase Family Biochemical and Biophysical Research Communications. ,vol. 204, pp. 930- 936 ,(1994) , 10.1006/BBRC.1994.2549
M. Christie, M. Landin-Olsson, G. Sundkvist, G. Dahlquist, �. Lernmark, S. B�kkeskov, Antibodies to a Mr-64000 islet cell protein in Swedish children with newly diagnosed Type 1 (insulin-dependent) diabetes Diabetologia. ,vol. 31, pp. 597- 602 ,(1988) , 10.1007/BF00264766
M.A Atkinson, N.K Maclaren, W.J Riley, D.W Sharp, P.E Lacey, 64,000 Mr autoantibodies as predictors of insulin-dependent diabetes. The Lancet. ,vol. 335, pp. 1357- 1360 ,(1990) , 10.1016/0140-6736(90)91241-2
C. F. Verge, N. J. Howard, M. J. Rowley, I. R. Mackay, P. Z. Zimmet, M. Egan, H. Hulinska, I. Hulinsky, R. A. Silvestrini, S. Kamath, A. Sharp, T. Arundel, M. Silink, Anti-glutamate decarboxylase and other antibodies at the onset of childhood IDDM: a population-based study Diabetologia. ,vol. 37, pp. 1113- 1120 ,(1994) , 10.1007/BF00418375
GianFranco Bottazzo, Alejo Florin-Christensen, Deborah Doniach, ISLET-CELL ANTIBODIES IN DIABETES MELLITUS WITH AUTOIMMUNE POLYENDOCRINE DEFICIENCIES The Lancet. ,vol. 304, pp. 1279- 1283 ,(1974) , 10.1016/S0140-6736(74)90140-8
William J. Riley, Noel K. Maclaren, Jeffrey Krischer, Rebecca P. Spillar, Janet H. Silverstein, Desmond A. Schatz, Sherwin Schwartz, John Malone, Shirish Shah, Constance Vadheim, Jerome I. Rotter, A prospective study of the development of diabetes in relatives of patients with insulin-dependent diabetes. The New England Journal of Medicine. ,vol. 323, pp. 1167- 1172 ,(1990) , 10.1056/NEJM199010253231704