{'fraction_non_alphanumeric': 0.036470588235294116, 'fraction_numerical': 0.02196078431372549, 'mean_word_length': 5.441919191919192, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
HLA‐C*06 and psoriasis: susceptibility, phenotype, course and response to treatment

In this issue of the BJD, Chen and Tsai review the diverse effects of the HLA-C*06 allele on psoriasis. The multifactorial aetiology of psoriasis includes a complex (i.e. non-Mendelian) genetic component, with the HLA-C*06 allele of the human leucocyte antigen (HLA) class I being the earliest and major candidate psoriasis susceptibility gene, designated ‘psoriasis susceptibility 1’ (PSORS1, OMIM 177900), on chromosome 6p21 3. The prevalence of HLA-C*06 ranges from 4% to 16% in healthy patients and from 10 5% to 77 2% in patients with psoriasis, depending on the population’s ethnicity. A metaanalysis confirmed that HLA-C*06 is strongly associated with psoriasis type 1, traditionally also defined as early-onset psoriasis (before 40 years) as opposed to late onset (after 40 years). HLA-C*06 encodes a major histocompatibility complex I (MHCI) receptor. MHCI molecules are fundamental receptors of the immune system, involved in the presentation of self and non-self peptides to T cells. The functions of HLA-C*06 in the pathogenesis of psoriasis have been recently elucidated. HLA-C*06 is able to bind psoriasis autoantigens such as the antimicrobial peptide LL-37 (also known as cathelicidin) and the melanocyte-expressed autoantigen ADAM TSlike protein 5 (ADAMTSL5). It also presents these autoantigens to T cells in psoriatic skin, thus eliciting an adaptive immune response. The HLA-C*06 allele may also affect clinical phenotype, including disease severity, associated comorbidities and response to treatment. HLA-C*06-positive patients with psoriasis experience more frequent exacerbations with throat infections and more frequently present guttate psoriasis. Other distinct features include a higher incidence of Koebner phenomenon, more extensive disease, less frequent dystrophic nail changes and more frequent remissions during pregnancy. Patients with psoriasis carrying HLA-C*06 also show better and more rapid response to ustekinumab than non-HLAC*06 carriers. Although clinical presentation, age of onset and response to treatment can vary greatly due to complex interactions between genetic, environmental and host factors in patients with psoriasis, it is likely that identification of HLA-C*06 carriers could contribute to predicting the course of the disease and allow better tailoring of follow-up and treatment strategies to the individual patient, in the setting of predictive, personalized and precision medicine. Conflicts of interest