TY - JOUR
T1 - LMP2 polymorphism is associated with extraspinal disease in HLA-B27 negative Caucasian and Mexican Mestizo patients with ankylosing spondylitis
AU - Maksymowych, Walter P.
AU - Sha, Tao
AU - Vaile, Jan
AU - Suarez-Almazor, Maria
AU - Ramos-Remus, Cesar
AU - Russell, Anthony S.
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 2000
Y1 - 2000
N2 - Objective. To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). Methods. Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity 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 patients 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), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLADR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior 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 susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.
AB - Objective. To determine the effects of HLA Class II genes, particularly LMP2 and previously implicated Class I genes, on susceptibility and disease expression in HLA-B27 negative ankylosing spondylitis (AS). Methods. Patients included 41 HLA-B27 negative Caucasians from a total AS population of 546 and 17 HLA-B27 negative Mexican Mestizo. Controls included 4352 random HLA-B27 negative Caucasians. LMP2 genotype assignments were made on all patients and 282 random Caucasian controls by polymerase chain reaction-restriction fragment length polymorphism with the Cfo I restriction enzyme while HLA typing was performed on patients and controls using microcytotoxicity 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 patients 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), even when those with colitis and psoriasis were excluded from analysis (ES+ 55.6% versus ES- 22.2%). This finding remained significant after stratification by HLADR. Similar trends were noted in the Mexican population. A potential role for HLA-DR8 and DR2 in susceptibility to disease was observed in Caucasian patients, although this observation requires confirmation. We could not confirm reported associations with HLA-B60 or B39. Peripheral arthritis was significantly more commonly observed in those who had had acute anterior 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 susceptibility and/or phenotype in HLA-B27 negative individuals similar to those noted in HLA-B27 positive AS. Eccentric and axial phenotypes of disease may be immunogenetically determined.
KW - Ankylosing spondylitis
KW - HLA-B27 negative
KW - LMP2 polymorphism
UR - http://www.scopus.com/inward/record.url?scp=0342470536&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0342470536&partnerID=8YFLogxK
M3 - Article
C2 - 10648037
AN - SCOPUS:0342470536
SN - 0315-162X
VL - 27
SP - 183
EP - 189
JO - Journal of Rheumatology
JF - Journal of Rheumatology
IS - 1
ER -