High T cell responses to the glutamic acid decarboxylase (GAD) isoform 67 reflect a hyperimmune state that precedes the onset of insulin-dependent diabetes
- Author(s)
- Honeyman, MC; Stone, N; DeAizpurua, H; Rowley, MJ; Harrison, LC;
- Details
- Publication Year 1997-04,Volume 10,Issue #2,Page 165-173
- Journal Title
- JOURNAL OF AUTOIMMUNITY
- Publication Type
- Journal Article
- Abstract
- Pancreatic islet beta-cell destruction leading to insulin-dependent diabetes mellitus (IDDM) is an autoimmune T cell-mediated process. Peripheral blood T cells, which proliferate to islet antigens such as glutamic acid decarboxylase (GAD), (pro)insulin or tyrosine phosphatase IA-2, can be detected in at-risk, first degree relatives of people with IDDM. However, cross-sectional studies cannot define the relationship between T cell responses and progression to IDDM. Longitudinal studies were therefore undertaken on 50 at-risk, first degree relatives tested at least yearly for up to 4 years, during which time five developed IDDM. Peripheral blood T cell responses to a GAD67(aa208-404)-glutathione-S-transferase (GST) fusion protein, GST, insulin and tetanus toroid were measured, together with antibodies to islet cells, GAD, insulin and IA-2. High levels of antibodies to GAD or insulin were generally associated with low T cell responses to these antigens. Relatives who developed IDDM were characterized by high levels of antibodies to insulin and/or islet cells, and high T cell responses to GAD67-GST and tetanus, but not insulin, in the 24 months before clinical diagnosis. Cross-sectionally, T cell responses to GAD67(aa208-404)-GST and to full-length GAD65-GST were highly correlated (r=0.75, P<0.002). In conclusion, increased cellular immunity to the mid region of GAD67 was a marker of late pre-clinical IDDM, but appears to reflect a more general, transient state of cellular immune hyperresponsiveness. (C) 1997 Academic Press Limited.
- Publisher
- ACADEMIC PRESS LTD
- Keywords
- BLOOD MONONUCLEAR-CELLS; RISK; ANTIBODIES; MELLITUS; IMMUNITY; AUTOANTIBODIES; PREDICTION; EXPRESSION; MOLECULES; PANCREAS
- Publisher's Version
- https://doi.org/10.1006/jaut.1996.0124
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- Refer to copyright notice on published article.
Creation Date: 1997-04-01 12:00:00