HLA-Cw6

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.

The worldwide frequency of the HLA-Cw6 allele varies widely, 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.

Furthermore, HLA-Cw6 has been associated with psoriasis guttata, Köbner phenomenon, and better response to methotrexate, interleukin (IL)-12/23, IL-17, and IL-23 targeted drugs. However, this difference in efficacy of ustekinumab was no longer significant in a post-hoc analysis of a pivotal phase III study (concerning ustekinumab) (Chen L et al 2018).

Recent studies have found an association between HLA-Cw1 and some Asian populations with psoriasis, particularly Southern Chinese. HLA-Cw1 positivity has been associated with erythrodermic psoriasis, pustular psoriasis, and 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). 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.

In the meantime, easy-to-perform tests are available for diagnostics, e.g. the EUROArray HLA-Cw6 Direct Test. This test was specially developed for the determination of HLA-C*06 alleles and is therefore extremely easy to perform compared to other molecular biological methods of HLA-C*06 detection. The unique direct method eliminates the need to isolate DNA: the whole blood sample is treated with two extraction reagents and can then be used directly in the PCR. The PCR primers have been selected and optimized to ensure that all relevant HLA-C*06 subtypes are detected by this test system.

Immunological and genetic studies have identified IL-17 and IL-23 as key factors in psoriasis pathogenesis. Targeting these cytokines and TNFα through biologic therapies has revolutionized the treatment of severe chronic plaque disease. Psoriasis currently cannot be cured, but treatment should aim to minimize physical and psychological damage by treating patients early in the disease process, identifying and preventing associated multimorbidity, initiating lifestyle changes, and using a personalized treatment approach (Griffiths CEM et al. 2021).

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. Huang YW et al (2021) HLA-Cw1 and psoriasis. Am J Clin Dermatol 22:339-347.