HLA-Cw1

Psoriasis is a multifactorial disease with a strong genetic background. HLA-Cw6 is one of the most strongly associated psoriasis susceptibility alleles. It has been repeatedly observed that the HLA-Cw6 allele influences disease progression, phenotypic features, severity, comorbidities, and treatment outcomes. However, the prevalence of HLA-Cw6 is much lower than that of HLA-Cw1 in some Asian countries (Huang YW et al. (2021).

HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and the axial type of psoriatic arthritis. Furthermore, HLA-Cw1 positive psoriatic patients appear to be more likely to be unresponsive to conventional therapies (Huang YW et al. 2021). However, no known trigger factor or autoantigen has been identified for HLA-Cw1 positivity.

However, HLA-Cw1 has been associated with some viral pathogens. Thus, cytotoxic T lymphocytes recognize several 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. Given the diverse pathogenesis of psoriasis and the different HLA-Cw prevalence in different ethnic groups, further studies are needed to confirm the role of HLA-Cw1 in psoriasis (Ho SS et al. 2022).

The worldwide frequency of the HLA-Cw6 allele also varies significantly, being generally higher in Caucasians than in Asians (Huang YW et al. 2021). The allele is associated with psoriasis type I , which occurs early. 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 this allele are more likely to have arms, legs, and trunk affected, and Köbner phenomenon is more common. Patients with psoriatic arthritis with HLA-Cw6 are more likely to have early disease onset and tend to present with cutaneous symptoms before musculoskeletal symptoms. HLA-Cw6-positive patients have been shown in several studies to respond better to methotrexate and ustekinumab. However, this difference in efficacy of ustekinumab was only moderate in a post-hoc analysis of a pivotal phase III trial (Chen L et al. 2018).

Of note, HLA-Cw1-negative patients were significantly more likely to respond to biologics (including etanercept, adalimumab, ustekinumab, secukinumab, ixekizumab , and guselkumab; odds ratio [OR] 1. 99, 95% confidence interval [CI] 1.17-3.44, p = 0.0122) and especially for ustekinumab (OR 3.27, 95% CI 1.03-11.30; p = 0.0496). HLA-Cw1-negative patients also showed significantly greater improvement in PASI scores with ustekinumab and biologics (p = 0.0044 and p = 0.0064, respectively), while other biologics showed nonsignificant trends. HLA-Cw1 status does not affect response to non-biologic systemic treatment, including phototherapy (Ho SS et al. 2022).

1. Chen L et al (2018) HLA-Cw6 and psoriasis. Br J Dermatol 178:854-862.
2. Griffiths CEM et al (2021) Psoriasis. Lancet 397(10281):1301-1315.
3. Gudjónsson JE et al. (2002) HLA-Cw6-positive and HLA-Cw6-negative patients with psoriasis vulgaris have distinct clinical features. J Invest Dermatol 118:362-365.
4. Ho SS et al (2022) Associations between HLA-Cw1 and Systemic Treatment Response of Asian Psoriasis Patients. Mol Diagn Ther 26: 541-549
5. Huang YW et al (2021) HLA-Cw1 and psoriasis. Am J Clin Dermatol 22:339-347.
6. Terui H et al. (2021) Pediatric psoriasis induced by HLA-B46-Cw1 haplotype: A retrospective study of psoriasis onset after hematopoietic stem cell transplantation. J Dermatol 48:1381-1385