HLA-Cw6 and psoriasis

Abstract

Psoriasis is a multifactorial disease with a strong genetic background. HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. It is repeatedly observed to affect disease course, phenotypic features, severity, comorbidities and treatment outcomes. To the best of our knowledge, the roles of HLA-Cw6 in psoriasis have not yet been thoroughly reviewed. The worldwide frequency of the HLA-Cw6 allele varies greatly, with it being generally higher in white people than in Asians. The allele is associated with type I early-onset psoriasis. Stress, obesity and streptococcal pharyngitis are commonly observed in HLA-Cw6-positive patients. Phenotypically, HLA-Cw6 has been found to be associated with guttate psoriasis. In addition, patients carrying the allele are more likely to have arm, leg and trunk involvement, and the Koebner phenomenon. Patients with psoriatic arthritis with HLA-Cw6 more often have early onset and tend to show cutaneous symptoms before musculoskeletal symptoms. HLA-Cw6-positive patients have been shown in several studies to be more responsive to methotrexate and ustekinumab. However, this difference in ustekinumab efficacy was only moderate in a post-hoc analysis of a pivotal phase III study. HLA-Cw6 positivity also tends to be less frequent in high-need patients who fail conventional therapy. Small studies have also investigated the role of HLA-Cw6 in remission of psoriasis during pregnancy, and with the comorbidities of photosensitivity and atherosclerosis. Given the diverse nature of psoriasis pathogenesis, as well as the difference of HLA-Cw6 positivity in different ethnic groups, more studies are needed to confirm the role of HLA-Cw6 in psoriasis.