LACK OF CORRELATION OF COPY NUMBER OF HLA DQA1A*05 DQB1*02 AND TISSUE TRANSGLUTAMINASE LEVELS IN UNTREATED CELIAC DISEASE

Abstract

Background: Celiac Disease is an autoimmune disorder of the small intestine characterized by intolerance to gluten. More than 90% of the patients with celiac disease have the human leukocyte antigen DQA1*05 DQB1*02. A gene dosage effect has been proposed for this high-risk genotype. In CD, there is an autoimmune response to the enzyme tissue transglutaminase, causing the production of immunoglobulin A autoantibodies, which are quantitative and resolve with improvement of intestinal inflammation after adherence to a gluten-free diet. Methods: Blood samples were collected from relatives of patients with known celiac disease as part of a family study to identify genes for celiac disease. These patients were screened for immunogloglobulin A endomysial antibodies. Positive sera were then evaluated for quantitative levels of immunoglobulin A tissue transglutaminase antibodies and HLA genotyping was performed. Results: One hundred sixteen family members were found to be positive for immunoglobulin A endomysial antibodies. Tissue transglutaminase levels for this group had a mean of 111 (±SD 93) with a range of 4-258. There was no correlation between IgA tTG levels and age or sex of the patients. Twelve patients had no copies of DQA1*05DQB1*02,82 had 1 copy, and 22 had 2 copies. The means for IgA tTG Ab levels for the 3 groups were (1) zero copies, mean = 129 Units (2) one copy, mean = 111 units (3) two copies, mean = 100 units. There were no statistical differences between the IgA tTG Ab levels in the 3 groups or when or when the presence of the DQB1*02 genotype alone was evaluated. Conclusion: HLA genotype, although it is strongly correlated with CD and does not correlate with the level of IgA tTG Ab.