Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly ... more Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity.
Previous studies have shown evidence for T lymphocytes specific for tissue transglutaminase (tTG)... more Previous studies have shown evidence for T lymphocytes specific for tissue transglutaminase (tTG) in the periphery of coeliac disease (CD) patients. These cells could play a role in disease pathogenesis and may be involved in providing help for the production of anti-tTG autoantibodies. The objective of this study was to further investigate the presence of tTG-specific T cells in patients with treated and untreated CD, and normal controls. Positive proliferative responses to three different commercial tTG antigens were detected in all groups tested, occurring more frequently and at higher levels in untreated CD patients. The addition of antibodies to HLA-DQ and HLA-DR caused a significant reduction in the proliferative response to tTG. T cell lines specific for tTG and composed predominantly of CD4-positive T cells were generated from responsive CD and control individuals, and were found to produce large amounts of interferon-γ, as well as interleukins 10, 17A, and 21.
Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly ... more Antibodies of the IgA class directed against the enzyme tissue transglutaminase (tTG) are highly specific for coeliac disease (CD). IgG antibodies to tTG also occur in CD, and have also been reported in autoimmune diseases such as type 1 diabetes mellitus and Crohn's disease. In comparison to the IgA anti-tTG response, little is known of the IgG anti-tTG response in terms of epitope specificity and IgG subclass usage. The aim of this study was to investigate and compare epitopes recognised by CD and non-CD IgG anti-tTG antibodies, and determine the relative proportions of the IgG subclasses comprising this response. IgG anti-tTG positive individuals who did not have CD were identified by screening groups of patients with type I diabetes mellitus, Crohn's disease and granulomatosis with polyangiitis. Results from ELISA blocking experiments and mutant tTG antigens demonstrate that non-CD IgG anti-tTG bind different epitopic determinants to CD IgG anti-tTG. The IgG subclass usage of coeliac disease and type 1 diabetes was dominated by IgG1, whereas this IgG subclass was infrequently a component of the IgG anti-tTG response in diseases such as granulomatosis with polyangiitis and Crohn's disease. The differences in epitope specificity and subclass usage of IgG anti-tTG observed between CD and non-CD individuals may be due to the differing mechanisms underlying tTG autoimmunity.
Previous studies have shown evidence for T lymphocytes specific for tissue transglutaminase (tTG)... more Previous studies have shown evidence for T lymphocytes specific for tissue transglutaminase (tTG) in the periphery of coeliac disease (CD) patients. These cells could play a role in disease pathogenesis and may be involved in providing help for the production of anti-tTG autoantibodies. The objective of this study was to further investigate the presence of tTG-specific T cells in patients with treated and untreated CD, and normal controls. Positive proliferative responses to three different commercial tTG antigens were detected in all groups tested, occurring more frequently and at higher levels in untreated CD patients. The addition of antibodies to HLA-DQ and HLA-DR caused a significant reduction in the proliferative response to tTG. T cell lines specific for tTG and composed predominantly of CD4-positive T cells were generated from responsive CD and control individuals, and were found to produce large amounts of interferon-γ, as well as interleukins 10, 17A, and 21.
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