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Value of antibodies to islet protein tyrosine phosphatase-like molecule in predicting type 1 diabetes.
Hawa, M; Rowe, R; Lan, M S; Notkins, A L; Pozzilli, P; Christie, M R; Leslie, R D.
Afiliación
  • Hawa M; Department of Diabetes and Metabolism, St. Bartholomew's Hospital, London, U.K.
Diabetes ; 46(8): 1270-5, 1997 Aug.
Article en En | MEDLINE | ID: mdl-9231650
Islet antigens associated with type 1 diabetes include a recently identified protein tyrosine phosphatase-like molecule IA-2, which contains the intracellular fragment IA-2ic. To determine whether combinations of antibodies including those to IA-2 characterize and predict type 1 diabetes, we studied antibodies to IA-2, IA-2ic, glutamic acid decarboxylase (GAD65), and islet cell antibodies (ICAs) in 1) 60 newly diagnosed type 1 diabetic patients followed for 1 year, 2) 31 monozygotic twin pairs discordant for type 1 diabetes followed up to 12 years (11 twins developed diabetes), 3) 18 dizygotic twin pairs discordant for type 1 diabetes, and 4) normal healthy control subjects. Newly diagnosed type 1 diabetic patients frequently had antibodies to IA-2 (62%), IA-2ic (67%), GAD65 (77%), and ICAs (85%). The intracellular fragment of IA-2 probably contains the immunodominant epitope as 137 of 143 samples with IA-2 antibodies from type 1 diabetic patients also had IA-2ic antibodies. Monozygotic twins were usually discordant for antibody specificities. Concordance was higher in monozygotic than matched dizygotic twins for both antibody combinations (33 vs. 6%, P < 0.05) and the development of diabetes (33 vs. 0%, P < 0.01). In monozygotic twins, all the antibodies were highly predictive of type 1 diabetes (positive predictive values all >87%), although antibodies were also detected in twins at low risk of disease. In summary, IA-2 emerges as a major antigen associated with type 1 diabetes and distinct from GAD65. Type 1 diabetes-associated autoimmunity, which is probably induced by environmental factors, does not necessarily herald progression to the disease. However, genetic factors may influence the development of combinations of disease-associated antibodies and the progression to type 1 diabetes.
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoantígenos / Islotes Pancreáticos / Proteínas Tirosina Fosfatasas / Diabetes Mellitus Tipo 1 / Proteínas de la Membrana Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Diabetes Año: 1997 Tipo del documento: Article Pais de publicación: Estados Unidos
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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoantígenos / Islotes Pancreáticos / Proteínas Tirosina Fosfatasas / Diabetes Mellitus Tipo 1 / Proteínas de la Membrana Tipo de estudio: Etiology_studies / Incidence_studies / Observational_studies / Prevalence_studies / Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Aged / Child / Child, preschool / Female / Humans / Male / Middle aged Idioma: En Revista: Diabetes Año: 1997 Tipo del documento: Article Pais de publicación: Estados Unidos