Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


HLA-Bw4 Alleles and HLA-C Alleles That Have High Cell-Surface Expression Are Associated with Susceptibility to Psoriatic Arthritis (PsA).

Chandran3,  Vinod, Pellett2,  Fawnda, Ayearst2,  Renise, Pollock3,  Remy, Gladman1,  Dafna D.

Toronto Western Hospital, Toronto, ON, Canada
University of Toronto Psoriatic Arthritis Clinic, Toronto Western Hospital, Toronto, ON, Canada
University of Toronto Psoriatic Arthritis Clinic, Toronto Western Hospital

Background:

Natural-Killer (NK) cells and NK-T cells are important in the pathogenesis of PsA. The killer-cell immunoglobulin-like receptors (KIRs) on NK cells regulate the inhibition and activation of NK-cell responses through recognition of HLA class I molecules on target cells. It was previously shown that individuals with KIR3DS1 and HLA-B alleles with the serological Bw4 epitope and amino acid isoleucine at position 80 (HLA Bw4 80Ile-B*1513, 1516, 1517, 1524, 2702, 3801, 4901, 51, 5201, 5301, 5302, 57, 58), as well as those with expressing HLA-C alleles that have high cell-surface expression (HLA-C Hi- C* 02, 05, 06, 08, 12, 15, 16) progress more slowly to AIDS. Given the important epidemiological relationship between PsA and AIDS we sought to determine whether these genotypes are associated with susceptibility to PsA.

Methods:

685 cases of European ethnicity (295 females, mean age 43 years, PsA duration 7 years, psoriasis duration 15 years, actively inflamed joint count 11, PASI score 5.2) with PsA and 706 ethnically matched controls (273 females, mean age 53 years) were recruited for the study. Genotyping for HLA-B, and -C alleles was performed using PCR-SSO reverse line blot and that for KIR genes was performed using PCR-SSP on genomic DNA obtained from peripheral blood. Association between genotypes and PsA was investigated using chi square, Mantel-Haenszel trend test and logistic regression.

Results:

HLA-Bw4 80Ile was associated with PsA with risk being higher in subjects with two Bw4 80Ile alleles compared to those with one or no alleles [Bw4 80Ile 2 copies vs. none OR = 1.91, p = 0.03; 1 copy vs. none OR = 1.61, p<0.0001, trend p <0.0001] independent of HLA-B*27. KIR3DS1 was not associated with PsA in univariate analysis (p=0.82), although in a multivariate logistic regression analysis including all KIR genes, KIR3DS1 was protective (OR=O.54, p = 0.038). Analysis for association of Bw4 80Ile and/or KIR3DS1 with PsA where the hierarchy of putative biological effects, namely, Bw4 80Ile absence and KIR3DS1 presence < absence of both Bw4 80Ile and KIR3DS1 < Bw4 80Ile presence and KIR3DS1 absence < presence of Bw4 80Ile and KIR3DS1 (highest risk group) was taken into account showed that the combined genotype was associated with PsA (p trend < 0.0003). HLA-C Hi alleles also were associated with PsA with risk being higher in subjects with two HLA-C Hi alleles compared to those with one or no alleles (C Hi two copies vs. none OR = 2.56, p <0.0001; 1 copy vs. none OR = 1.49, p=0.0012, trend p <0.0001) independent of HLA-C*06, KIR2DS1 and KIR2DS2. Multivariate regression analysis including both Bw4 80Ile and C Hi alleles in a logistic model revealed that both HLA-Bw4 80Ile and HLA-C Hi are independently associated with susceptibility to PsA.

Conclusions:

HLA and KIR genes that are associated with better control of HIV/AIDS are independently associated with increased susceptibility to PsA.

To cite this abstract, please use the following information:
Chandran, Vinod, Pellett, Fawnda, Ayearst, Renise, Pollock, Remy, Gladman, Dafna D.; HLA-Bw4 Alleles and HLA-C Alleles That Have High Cell-Surface Expression Are Associated with Susceptibility to Psoriatic Arthritis (PsA). [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1975
DOI: 10.1002/art.29740

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