HLA associations reveal genetic heterogeneity in psoriatic arthritis and in the psoriasis phenotype

Abstract

These findings suggest that the psoriasis phenotype results from two patterns of MHC effect. The first involves the classic psoriasis susceptibility gene C*06, which confers more penetrant skin disease with less prevalent and more time-dependent musculoskeletal phenotype development. The second pattern appears to be mediated by HLA-B alleles, notably B*27, and includes temporally more coincident musculoskeletal involvement that is nearly equivalent in penetrance to that of the skin disease.

Promoting patient‐centred care in psoriatic arthritis: a multidisciplinary European perspective on improving the patient experience

“…Though no absolute indicators have been identified to predict that a person with psoriasis may develop PsA, the presence of soluble biomarkers, for example, highly sensitive C‐reactive protein (hsCRP), osteoprotegerin (OPG), matrix metalloproteinase‐3 (MMP‐3) and the C‐propeptide of type II collagen to collagen fragment neoepitopes Col2‐3/4 long mono ratio or certain susceptibility genes (e.g. certain human leucocyte antigen alleles [HLA‐B and HLA‐C]) may confer susceptibility to PsA among patients with psoriasis 9, 10, 11, 12. Moreover, the predictive nature of clinical observations such as the severity of psoriasis (as measured by the Psoriasis Area Severity Index [PASI]), the severity of joint involvement and the presence of certain psoriasis features (e.g.…”

Epidemiology, genetics and management of psoriatic arthritis 2013: focus on developments of who develops the disease, its clinical features, and emerging treatment options

“…13,14 The current studies of PsA susceptibility having psoriasis control cohorts find the same values for the frequency of HLA-C*06:02, eg, 57.5%. 9 The representation of HLA-C*06:02 in PsA…”

“…9 The answer to the question of to what extent does the MHC contribution to PsA susceptibility resemble that of cutaneous psoriasis, was that in PsA cases presenting to a rheumatology unit, the frequency of HLA-C*06:02 was 28.7%, a value that was significantly lower than in the psoriasis cohort (57.5%, P = 9.9 -12 ). This heterogeneity in MHC genes between the cohorts allowed rejection of the hypothesis that the psoriasis phenotype is genetically homogeneous, and we conclude that the psoriasis phenotype and specifically PsA is genetically heterogeneous.…”

“…17 Three haplotypes containing B*27 or B*39:01 were significantly increased in frequency in the PsA cohort, 15.6% versus 5.5% in reference controls, but were not increased in the psoriasis cohort (4.7%). 9 Since the EH27.1 and EH27.2 haplotypes associated with PsA susceptibility share the same B*27 allele but differ in their HLA-C alleles, this strongly suggests this susceptibility maps to the HLA-B locus and to the B*27 allele itself. Furthermore, the structural and functional similarities between the molecules encoded by B*39:01 and B*27 also point to a role of the HLA-B alleles.…”

“…The molecule encoded by shared HLA-C*12 alleles could be an alternative explanation, however the B18 allele, which is also present on a C*12 haplotype, is not increased in frequency in PsA: 5.8% versus 6.1% in reference controls. 9 Influence of HLA alleles on the risk of an individual with psoriasis to develop PsA…”