HLA-C Locus Alleles May Modulate Clinical Expression of Psoriatic Arthritis
Abstract and Introduction
The aim of the present study was to evaluate the relative contribution of human leukocyte antigen (HLA)-C locus alleles in determining the risk and the clinical expression of psoriatic arthritis (PsA). One hundred PsA patients were randomly selected and grouped into three disease subsets: oligoarthritis (n = 40), polyarthritis (n = 25) and spondylitis (n = 35). The HLA-C locus profile of this cohort was studied by methods based on molecular biology and was compared with that of 45 patients with psoriasis vulgaris and 177 healthy blood donors from the same ethnic origin. HLA-Cw*0602 was found associated with both psoriasis (odds ratio (OR) 6.2; 95% confidence interval (CI) 3.1 to 12.5; p < 0.0001) and PsA (OR 6.2; 95% CI 3.6 to 10.8; p < 0.0001); however, this allele was equally found among the PsA subsets. HLA-Cw6-positive patients showed a longer psoriasis-arthritis latency period (p = 0.012). HLA-Cw*0701 was found under-represented in PsA in comparison with controls (OR 0.5; 95% CI 0.3 to 0.9; p = 0.04), as was HLA-Cw*0802 (OR 0.3; 95% CI 0.08 to 1; p = 0.05). A positive association was found between psoriatic spondylitis and HLA-Cw*0702 (OR 5.0; 95% CI 1.4 to 25; p = 0.01). HLA-Cw*0602 seems to confer a general risk for psoriasis, but the presence of other HLA-C locus alleles may explain an additional arthritogenic risk. HLA-C alleles may modulate some aspects of the clinical expression of PsA, but these findings need confirmation.
It is thought that the development of psoriatic arthritis (PsA) is related to an interaction between several genetic, immunological and environmental elements, and there is now convincing evidence to support this view.
Although the inheritance of psoriasis seems to be polygenic, previous studies have localized the PSORS1 (psoriasis susceptibility 1 gene) locus to the proximal MHC (major histocompatibility complex) class I region. Approximately a dozen genes in this region have so far been genetically inseparable, but very recent studies suggest that among them, human leukocyte antigen (HLA)-Cw6 itself is the true psoriasis gene. In addition, this gene is also relevant to modulation of the clinical expression of psoriasis, as demonstrated by the fact that HLA-Cw6-positive patients show an earlier disease onset and more family aggregation than those without it.
Genetic factors are also important in both susceptibility to and the expression of PsA; however, genetic association studies of PsA are limited, among other factors, by its changing articular pattern over time and the known phenomenon of linkage disequilibrium between genes. The latter may explain why some HLA genes originally associated with PsA susceptibility are now being considered part of the ancestral haplotypes related to psoriasis risk rather than true associations. Moreover, it has been difficult to discover whether HLA-Cw6 itself is associated with PsA, because this is the primary marker for psoriasis and most patients with PsA have cutaneous psoriasis; in contrast, some recent investigations have shown that both conditions share a 100-kilobase susceptibility region telomeric to HLA-C.
Few studies have investigated the potential role of HLA-C locus alleles in the clinical expression of PsA, so this study was undertaken to determine the relative contribution of HLA-C alleles to psoriasis and PsA susceptibility, and as a subsidiary purpose to evaluate whether these alleles confer some additional clinical feature on this disease.