HLA class I and II alleles and susceptibility to generalized pustular psoriasis: significant associations with HLA-Cw1 and HLA-DQB1*0303.
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.
Ozawa
A
A
Department of Dermatology, Tokai University School of Medicine, Kanagawa, Japan.
Miyahara
M
M
Sugai
J
J
Iizuka
M
M
Kawakubo
Y
Y
Matsuo
I
I
Ohkido
M
M
Naruse
T
T
Ando
H
H
Inoko
H
H
Kobayashi
H
H
Ohkawara
A
A
Takahashi
H
H
Iizuka
H
H
Morita
E
E
Yamamoto
S
S
Hide
M
M
Taniguchi
Y
Y
Shimizu
M
M
D000595:Amino Acid Sequence; D017951:Antigen Presentation; D016009:Chi-Square Distribution; D018076:DNA, Complementary / Q000032:analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015788:HLA-A1 Antigen / Q000032:analysis / Q000235:genetics*; D015789:HLA-A2 Antigen / Q000032:analysis / Q000235:genetics*; D015236:HLA-C Antigens / Q000032:analysis / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D012016:Reference Values; D012680:Sensitivity and Specificity; D012698:Serologic Tests
D018076:DNA, Complementary; D015788:HLA-A1 Antigen; D015789:HLA-A2 Antigen; D015236:HLA-C Antigens; C047431:HLA-Cw1 antigen; D006683:HLA-DQ Antigens