The relationship between humoral and cellular immunity to IA-2 in IDDM
| Autor: | Desmond A. Schatz, Michael S. Lan, Jin-Xiong She, Clive Wasserfall, Eric W. Ottendorfer, Noel K. Maclaren, Abner Louis Notkins, Tamir M. Ellis, Mark A. Atkinson, Patricia J. Salisbury |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Adult
Cellular immunity medicine.medical_specialty Adolescent Endocrinology Diabetes and Metabolism Biology Lymphocyte Activation medicine.disease_cause Autoantigens Autoimmunity Immune system Antigen Internal medicine Immunopathology Internal Medicine medicine Humans Receptor-Like Protein Tyrosine Phosphatases Class 8 Antigens Phytohemagglutinins Child Autoantibodies Protein Tyrosine Phosphatase Non-Receptor Type 1 Autoimmune disease Immunity Cellular Autoantibody Membrane Proteins Middle Aged medicine.disease Diabetes Mellitus Type 1 Endocrinology Child Preschool Antibody Formation Humoral immunity Immunology Leukocytes Mononuclear Protein Tyrosine Phosphatases |
| Zdroj: | Diabetes. 47:566-569 |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/diabetes.47.4.566 |
| Popis: | Autoantibodies to the neuroendocrine protein insulinoma-associated protein 2 (IA-2), a member of the tyrosine phosphatase family, have been observed in individuals with or at increased risk for IDDM. Because this disease is thought to result from a T-cell-mediated autoimmune destruction of the insulin-producing pancreatic beta-cells, we analyzed humoral and cellular immune reactivity to this autoantigen to further define its role in the pathogenesis of IDDM. Peripheral blood mononuclear cells (PBMC) from individuals with newly diagnosed IDDM or at varying levels of risk for the disease were stimulated in vitro with the entire 42-kDa internal domain of IA-2 (amino acids 603-979), a series of control antigens (glutathionine-S-transferase, tetanus toxoid, Candida albicans, mumps, bovine serum albumin), and a mitogen (phytohemagglutinin). The frequency and mean stimulation index of PBMC proliferation against IA-2 was significantly higher in newly diagnosed IDDM subjects (14 of 33 [42%]; 3.8+/-4.5 at 10 microg/ml) and autoantibody-positive relatives at increased risk for IDDM (6 of 9 [66%]; 3.9+/-3.2) compared with autoantibody-negative relatives (1 of 15 [7%]; 1.8+/-1.0) or healthy control subjects (1 of 12 [8%]; 1.5+/-1.0). The frequencies of cellular immune reactivities to all other antigens were remarkably similar between each subject group. Sera from 58% of the newly diagnosed IDDM patients tested were IA-2 autoantibody positive. Despite investigations suggesting an inverse association between humoral and cellular immune reactivities against islet-cell-associated autoantigens, no such relationship was observed (rs=0.18, P=0.39) with respect to IA-2. These studies support the autoantigenic nature of IA-2 in IDDM and suggest the inclusion of cellular immune responses as an adjunct marker for the disease. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|