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F. Mackensen, J.D. Reveille, J.R. Smith, J.E. Coffman, L. Diekman, T.M. Doyle, N.K. Wade, R.D. Levinson, J.T. Rosenbaum, T.M. Martin; The MHC Class II Haplotype HLA–DRB1*0801/DQA1*0401/DQB1*0402 Is Associated With Acute Anterior Uveitis . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3480.
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Purpose: Acute anterior uveitis (AAU) is the most comon form of uveitis. It occurs in ∼40% of patients with ankylosing spondylitis (AS), and both diseases are known to be associated with HLA–B27. The aim of the study was to further determine HLA–haplotypes of patients with AAU compared to a healthy control group. Methods: We examined HLA alleles of 72 unrelated Caucasian patients with AAU (diagnosis verified by ophthalmology chart review) and of 250 healthy North American Caucasians. Patients were recruited from our clinics, the Spondylitis Association of America, and individual physicians, including members of the North American Spondylitis Consortium. HLA typing/subtyping was performed by Secondary Structural Content Prediction (SSCP), oligotyping and direct sequencing. Percentages below are allele frequencies. Statistical analysis was performed by the Fisher’s Exact test. Results: Twenty–five of the 72 AAU patients also had AS, 17 others reported symptoms consistent with AS and 30 did not have AS. As expected, HLA–B27 was prominent in the AAU cohort (62 positive, 2 negative and 8 of unknown HLA–B27 status). This is in contrast to healthy Caucasian populations where only 8–10% are HLA–B27 positive. In addition to HLA–B27, differences in HLA class II haplotypes were noted. From the 72 patients included, 126 alleles have been identified to date. A strong association for AAU was observed with DRB1*0801/DQA1*0401/DQB1*0402 (16/126, 12.7% vs. 13/500, 2.6%, P <0.0001) with a relative risk of 2.99 (95% confidence interval 2.07 to 4.33). Conversely, there was an inverse association with AAU for the haplotype DRB1*0301/DQA1*0501/DQB1*0201 (6/126, 4.8% vs. 60/500, 12.0%, P = 0.015). Conclusions: These data confirm and expand on a reported HLA–DR8 AAU association in an AS cohort (1998. Arthritis Rheum. 41:460). HLA class II haplotypes, mainly DRB1*0801/DQA1*0401/DQB1*0402, may influence uveitis risk.
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