HLA-Cw1 and Psoriasis.

Am J Clin Dermatol

Department of Dermatology, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei City, Taiwan.

Published: May 2021

Psoriasis is a chronic inflammatory skin condition with regional and ethnic differences in its prevalence and clinical manifestations. Human leukocyte antigen (HLA)-Cw6 is the disease allele conferring the greatest risk to psoriasis, but its prevalence is lower in Asian individuals. Recent studies have found associations between HLA-Cw1 and some Asian populations with psoriasis, especially Southern Chinese. HLA-Cw6 was associated with type I early-onset psoriasis, guttate psoriasis, Koebner phenomenon, and better response to methotrexate, interleukin (IL)-12/23, IL-17, and IL-23 targeting drugs. In contrast, HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and the axial type of psoriatic arthritis. Furthermore, HLA-Cw1 was more frequently associated with high-need patients who did not respond to conventional therapies. No known trigger factor nor autoantigen has been identified for HLA-Cw1 positivity. However, HLA-Cw1 has been linked to some viral agents. For example, cytotoxic T lymphocytes recognize multiple cytomegalovirus pp65-derived epitopes presented by HLA alleles, including HLA-C*01:02. In addition, cytomegalovirus can lead to severe exacerbation of psoriatic skin disease. The proposed interaction between viral infection, HLA-Cw1, and psoriasis is through the killer cell immunoglobulin-like receptors of natural killer cells. Given the diverse nature of psoriasis pathogenesis and the difference in HLA-Cw prevalence in different racial groups, more studies are needed to confirm the role of HLA-Cw1 in psoriasis.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812566PMC
http://dx.doi.org/10.1007/s40257-020-00585-1DOI Listing

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Article Synopsis
  • - Psoriasis is a chronic inflammatory skin disease linked to genetics, particularly the HLA-Cw6 gene, but HLA-Cw1 may also influence treatment responses, especially in some Asian populations where HLA-Cw6 is less common
  • - A study involving 126 psoriasis patients found that those who are HLA-Cw1-negative had a significantly better response to biologic treatments like ustekinumab, with evidence of improved severity scores compared to HLA-Cw1-positive patients
  • - The research suggests a connection between HLA-Cw1 status and the effectiveness of biologic therapies, but no impact on non-biologic treatments, indicating a need for further investigation into HLA-Cw1's specific role in psoriasis
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Genome-wide association studies have identified more than 60 susceptibility loci for psoriasis, highlighting the role of genetics in psoriasis development. Although the HLA region is suggested as the most prominent susceptibility locus, the role of the HLA haplotype in the development of psoriasis is unclear. The aim of this study is to investigate how HLA haplotype changes affect the onset of psoriasis and which HLA haplotypes are associated with the development of psoriasis.

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HLA-Cw1 and Psoriasis.

Am J Clin Dermatol

May 2021

Department of Dermatology, National Taiwan University Hospital, No. 7 Chung San South Road, Taipei City, Taiwan.

Psoriasis is a chronic inflammatory skin condition with regional and ethnic differences in its prevalence and clinical manifestations. Human leukocyte antigen (HLA)-Cw6 is the disease allele conferring the greatest risk to psoriasis, but its prevalence is lower in Asian individuals. Recent studies have found associations between HLA-Cw1 and some Asian populations with psoriasis, especially Southern Chinese.

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Background: Genetic predisposition to psoriasis, an inflammatory skin disease affecting 0·2-4% of the world population, is well established. Thus far, 41 psoriasis susceptibility loci reach genome-wide significance (P ≤ 5 × 10(-8) ). Identification of genetic susceptibility loci in diverse populations will help understand the underlying biology of psoriasis susceptibility.

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Earlier studies have shown that psoriasis in Japan and Thailand is associated with two different major histocompatibility complex (MHC) haplotypes - those bearing HLA-Cw6 and those bearing HLA-Cw1 and HLA-B46. In an independent case-control sample from Thailand, we confirmed the association of psoriasis with both haplotypes. No association was seen in Thai HLA-Cw1 haplotypes lacking HLA-B46, nor was HLA-Cw1 associated with psoriasis in a large Caucasian sample.

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