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.

Adaptive and Innate Immunity in Psoriasis and Other Inflammatory Disorders

“…Since it was shown in the late 1970s that psoriasis can be ameliorated by cyclosporin A (10), it can no longer be seriously denied that T lymphocytes play a central role in the pathogenesis of this disease. This view is substantiated by numerous subsequent observations over the past four decades: psoriasis can be precipitated by bone marrow transplantation (11) and, similar to other autoinflammatory diseases, the disease is frequently associated with certain HLA expression patterns (7, 12–14). Drugs that specifically inhibit the function of T lymphocytes (such as CD2 blockade in the early days of biologics) can improve psoriasis (15).…”

The Interleukin-23/Interleukin-17 Axis Links Adaptive and Innate Immunity in Psoriasis

“…Patients with given HLA genotypes can be assigned to certain clinical characteristics of psoriasis as well as functional immunological parameters. Likewise, the detection of certain autoantigens depends on HLA genotypes such as HLA-C*06:02 ( 6 ). Potential autoantigens in psoriasis include peptide fragments of keratin 17 with sequence homologies to streptococcal M-proteins ( 7 , 8 ), the antimicrobial peptide LL37 ( 9 ), and the melanocytic autoantigen ADAMTSL5 ( 10 ).…”

Koebner phenomenon leading to the formation of new psoriatic lesions: evidences and mechanisms

“…Nevertheless, the Koebner phenomenon is best described in association with psoriasis and there have been a number of studies showing the association of Koebnerization with psoriasis [11,12]. The occurrence of psoriatic lesions at unusual areas of the body regions such as on penis, around eyes, and on keloids suggest that the Koebner phenomenon may be responsible for these psoriatic lesions [13][14][15].…”