HLA Class I and II Alleles and Susceptibility to Generalized Pustular Psoriasis: Significant Associations with HLA‐Cw1 and HLA‐DQB1*0303

Abstract

HLA alleles in generalized pustular psoriasis (GPP) were investigated to clarify the etiology and/or pathogenesis of this disease. Not only serological typing of HLA class I and II antigens but also genotyping of HLA class II alleles were carried out in twenty-six unrelated Japanese patients with GPP. These patients were classified according to their history of psoriasis vulgaris (PV). Serological typing revealed a significantly high incidence of HLA-Cw1 (Pc = 0.04) in the patients as compared with Japanese healthy controls. The frequency of HLA-B46 was particularly high in the patients with GPP and a previous history of PV. Genotyping of HLA class II alleles showed a highly significant increase in HLA-DQB1*0303 (Pc = 0.01) in the patients vs. the healthy controls. In particular, HLA-DQB1*0303 was significantly more frequent in the patients with no prior history of PV than in those with a history of PV. Analysis on linkage disequilibrium showed remarkably different patterns for HLA class II haplotypes between the patients and the healthy controls. Based on the comparative analysis among the amino acid sequences of the beta 1-domain of the HLA-DQB1*03 alleles, proline at residue 55 was suggested to be important as a common amino acid for determination of the susceptibility to GPP. These results revealed not only an association between the etiology and/or pathogenesis of GPP and HLA, but also different mechanisms of the immune response between the patients with GPP and PV.

Genome-wide association scan yields new insights into the immunopathogenesis of psoriasis

“…The association of guttate psoriasis with HLA-Cw6 is even stronger than it is for chronic plaque psoriasis 12. Generalized pustular psoriasis manifests the same HLA associations found in plaque-type psoriasis 13. In contrast, palmoplantar pustulosis is not associated with HLA-Cw6 14 and is only rarely associated with typical psoriatic plaques.…”

A Case of Generalized Pustular Psoriasis Associated with Turner Syndrome

“…In addition, a higher frequency of HLA-DQB1*0303 susceptible alleles is present in GPP patients without a previous history of psoriasis vulgaris than in normal healthy controls (8). Our recent observation demonstrated that there is a weak association between a G to A conversion at nucleotide-308 of the TNF-α gene promotor and the characteristic features of GPP in the Japanese population (9).…”

“…The etiology of GPP is still incompletely understood; however, ample evidence suggests a close relationship between the distinct HLA haplotype, HLA-B27 and HLA-CW-1, and the genetic background of the disease (7,8). In addition, a higher frequency of HLA-DQB1*0303 susceptible alleles is present in GPP patients without a previous history of psoriasis vulgaris than in normal healthy controls (8).…”

Genetic associations of psoriasis in a Pakistani population

“…HLA‐Cw6 showed the strongest association (OR 2·43, P = 2·3 × 10 −12 ), consistent with previous reports. Interestingly, HLA‐Cw1 , which previously was shown to be associated with psoriasis in Thailand and Japan, showed marginally significant association (OR 1·66, P = 0·049), suggesting that the HLA‐Cw1‐B46 risk haplotype may be present in the Pakistani population. Three other loci ( IL13 , NOS2 , TRAF3IP2 ) showed nominally significant allelic associations (OR 1·35, 1·29, 1·70; P = 0·006, 0·0097, 0·0017, respectively).…”