The influence of genetic factors on the clinical manifestations and response to systemic treatment of plaque psoriasis

Abstract

Plaque psoriasis is a common, chronic, papulosquamous skin disorder. TNF, IL-17 and IL-23 have been identified as key cytokines in the pathogenesis of psoriasis. Certain human leukocyte antigen (HLA) variants, such as HLA-Cw6 and HLA-B27, were proposed to affect the clinical course of the disease and the response to standard and biological treatment. In individuals positive for HLA-B27, psoriatic arthritis tends to progress more rapidly, with a higher prevalence of dactylitis and nail changes, suggesting HLA-B27 being a genetic biomarker for early-onset psoriatic arthritis. HLA-Cw6 is associated with the early onset of cutaneous manifestations in psoriasis. In these cases, cutaneous lesions are commonly localised on the chest and limbs, with less pronounced scalp and nail involvement. Psoriatic arthritis tends to develop later in HLA-Cw6-positive patients. The presence of HLA-Cw6 is associated with a more favourable therapeutic response to methotrexate and p40IL-12/23 inhibitors than to TNF inhibitors. Therefore, HLA-Cw6 testing may be a valuable tool for identifying patients who are likely to benefit from treatment with specific monoclonal antibodies, especially p40IL-12/23 inhibitors.