Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

Chandra, Aditi; Lahiri, Anirudhya; Senapati, Swapan; Basu, Baidehi; Ghosh, Saurabh; Mukhopadhyay, Indranil; Behra, Akhilesh; Sarkar, Sonali; Chatterjee, Gobinda; Chatterjee, Raghunath

doi:10.1038/srep24059

Cited by 29 publications

(12 citation statements)

References 52 publications

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“…This highlights the need to use population-specific reference panels made by deep sequencing to impute MHC alleles and amino acids ( 8 ). The strong psoriasis risk of HLA-C*06:02 allele has been validated in worldwide populations including Europeans ( 17 , 20 ), East ( 6 , 21 ), and South Asians ( 22 ), with odds ratios of as high as 3.0–10.0. HLA fine-mapping analysis using the HLA imputation method successfully identified multiple other less obviously associated HLA-class I and class II variants that confer psoriasis risk independently from HLA-C*06:02 ( 20 ).…”

Section: Hla-class I Association Of Psoriasis: the Main Genetic Riskmentioning

confidence: 99%

Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis

Prinz

2018

Front. Immunol.

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Psoriasis is a complex immune-mediated inflammatory skin disease characterized by T-cell-driven epidermal hyperplasia. It occurs on a strong genetic predisposition. The human leukocyte antigen (HLA)-class I allele HLA-C*06:02 on psoriasis susceptibility locus 1 (PSORS1 on 6p21.3) is the main psoriasis risk gene. Other HLA-class I alleles encoding HLA molecules presenting overlapping peptide repertoires show associations with psoriasis as well. Outside the major histocompatibility complex region, genome-wide association studies identified more than 60 psoriasis-associated common gene variants exerting only modest individual effects. They mainly refer to innate immune activation and the interleukin-23/Th/c17 pathway. Given their strong risk association, explaining the role of the HLA-risk alleles is essential for elucidating psoriasis pathogenesis. Psoriasis lesions develop upon epidermal infiltration, activation, and expansion of CD8+ T cells. The unbiased analysis of a paradigmatic Vα3S1/Vβ13S1-T-cell receptor from a pathogenic epidermal CD8+ T-cell clone of an HLA-C*06:02+ psoriasis patient had revealed that HLA-C*06:02 directs an autoimmune response against melanocytes through autoantigen presentation, and it identified a peptide form ADAMTS-like protein 5 as an HLA-C*06:02-presented melanocyte autoantigen. These data demonstrate that psoriasis is an autoimmune disease, where the predisposing HLA-class I alleles promote organ-specific inflammation through facilitating a T-cell response against a particular skin-specific cell population. This review discusses the role of HLA-class I alleles in the pathogenic psoriatic T-cell immune response. It concludes that as a principle of T-cell driven HLA-associated inflammatory diseases proinflammatory traits promote autoimmunity in the context of certain HLA molecules that present particular autoantigens.

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Section: Hla-class I Association Of Psoriasis: the Main Genetic Riskmentioning

confidence: 99%

Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis

Prinz

2018

Front. Immunol.

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“…The worldwide HLA‐Cw6 allele frequency varies greatly and can range from 14·1% to 59·1%, whereas the percentage of patients with psoriasis carrying HLA‐Cw6 ranges from 10·5% to 77·2% (Table ) . Such wide ranges may be attributed to small sample sizes, ethnic diversity and differences in inclusion criteria.…”

Section: Hla‐cw6 Allele Frequency In Patients With Psoriasismentioning

confidence: 99%

HLA-Cw6 and psoriasis

Chen

Tsai

2018

British Journal of Dermatology

133

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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.

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“…PsV risk within MHC was originally mapped to a critical region at MHC class I, termed PSORS1 (Tiilikainen et al, 1980); then, HLA-C*06:02 was identified as the causal allele that explains the risk of PSORS1 (Nair et al, 2006). The strong PsV risk of HLA-C*06:02 allele has been validated in worldwide populations including Europeans (Lenz et al, 2015;Okada et al, 2014a), South Asians (Chandra et al, 2016), and East Asians (Mabuchi et al, 2014;Zhou et al, 2016), with an odds ratio (OR) of as high as 3.0e10.0. However, the genetic landscape of PsV within MHC has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

Hirata

Hirota

Ozeki

et al. 2018

Journal of Investigative Dermatology

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Psoriasis vulgaris (PsV) is an autoimmune disease of skin and joints with heterogeneity in epidemiologic and genetic landscapes of global populations. We conducted an initial genome-wide association study and a replication study of PsV in the Japanese population (606 PsV cases and 2,052 controls). We identified significant associations of the single nucleotide polymorphisms with PsV risk at TNFAIP3-interacting protein 1and the major histocompatibility complex region (P = 3.7 × 10 and 6.6 × 10, respectively). By updating the HLA imputation reference panel of Japanese (n = 908) to expand HLA gene coverage, we fine-mapped the HLA variants associated with PsV risk. Although we confirmed the PsV risk of HLA-C*06:02 (odds ratio = 6.36, P = 0.0015), its impact was relatively small compared with those in other populations due to rare allele frequency in Japanese (0.4% in controls). Alternatively, HLA-A*02:07, which corresponds to the cysteine residue at HLA-A amino acid position 99 (HLA-A Cys99), demonstrated the most significant association with PsV (odds ratio = 4.61, P = 1.2 × 10). In addition to HLA-A*02:07 and HLA-C*06:02, stepwise conditional analysis identified an independent PsV risk of HLA-DQβ1 Asp57 (odds ratio = 2.19, P = 1.9 × 10). Our PsV genome-wide association study in Japanese highlighted the genetic architecture of PsV, including the identification of HLA risk variants.

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Increased Risk of Psoriasis due to combined effect of HLA-Cw6 and LCE3 risk alleles in Indian population

Cited by 29 publications

References 52 publications

Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis

Human Leukocyte Antigen-Class I Alleles and the Autoreactive T Cell Response in Psoriasis Pathogenesis

HLA-Cw6 and psoriasis

Variants at HLA-A, HLA-C, and HLA-DQB1 Confer Risk of Psoriasis Vulgaris in Japanese

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