LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis

Objective. To determine the effects of HLA Class II genes, particularly LMP 2 and previously implicated Class I genes, on susceptibility and disease ex pression in HLA-B27 negative ankylosing spondylitis (AS). Methods, Patients included 41 HLA-B27 negative Caucasians from a total AS p opulation of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were ma de on all patients and 282 random Caucasian controls by polymerase chain re action-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microc ytotoxicity assays for Class I, and sequence specific probe-PCR for HLA-B60 , B39, B38, and DR. Results, The LMP2BB genotype was significantly decreased in Caucasian AS pa tients without extraspinal (ES) disease (25%) compared to AS patients with ES (64.7%) (p = 0.01) and random Caucasian controls (53.9%) (p = 0.007), ev en when those with colitis and psoriasis were excluded from analysis (ES 55.6% versus ES - 22.2%). This finding remained significant after stratific ation by HLA-DR. Similar trends were noted in the Mexican population. A pot ential role for HLA-DR8 and DR2 in susceptibility to disease was observed i n Caucasian patients, although this observation requires confirmation. We c ould nor confirm reported associations with HLA-B60 or B39. Peripheral arth ritis was significantly more commonly observed in those who had had acute a nterior uveitis (AAU) (75%) than in those who had not developed AAU (27.3%) (p = 0.04). Conclusion. HLA Class II encoded genes may have effects on disease suscepti bility and/or phenotype in HLA-B27 negative individuals similar to those no ted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may b e immunogenetically determined.