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 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 HLA-DR. 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).


CONCLUSIONS
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.
Maksymowych
W P
WP
Department of Medicine, University of Alberta, Edmonton, Canada.
Tao
S
S
Vaile
J
J
Suarez-Almazor
M
M
Ramos-Remus
C
C
Russell
A S
AS
D000328:Adult; D000368:Aged; D000483:Alleles; D003546:Cysteine Endopeptidases; D004198:Disease Susceptibility; D005260:Female; D005838:Genotype; D015796:HLA-B27 Antigen / Q000097:blood*; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D008800:Mexico; D008875:Middle Aged; D010641:Phenotype; D011110:Polymorphism, Genetic; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D044469:Racial Groups; D013167:Spondylitis, Ankylosing / Q000097:blood / Q000235:genetics* / Q000276:immunology
D015796:HLA-B27 Antigen; D011506:Proteins; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases