Michihiro Hide

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 β1‐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.

Regulation of inflammation in urticaria.

Urticaria is characterized by wheal and flare, which usually disappear within several hours. However, there are some cases with severe and/or prolonged eruptions lasting more than 24 hours and resistant to treatments by ordinary histamine antagonists. Histology of such cases accompanies various cell infiltrations, such as eosinophils and neutrophils. In order to know the mechanism of such infiltrations, we studied the release of chemotactic activities from skin slices for neutrophils and eosinophils. The factor was identified with LTB4 by HPLC analysis and released either by antigens or substance P. Moreover, studies with skin chambers on patients with chronic urticaria revealed spontaneous release of substance P, suggesting the involvement of neuropeptides in the pathogenesis of chronic urticaria. Incubation of skin slices with dexamethasone scarcely inhibited histamine release, but almost abolished release of LTB4 in response to antigens. Recently-developed histamine H1-antagonists, called anti-allergic drugs, inhibited both degranulation and TNFα releases from rat mast cell (RBL-2H3) line, but concentrations required to inhibit TNFα release was about one tenth of those to inhibit degranulation. Inhibition of LTB4 and TNFα from mast cells may partially account for clinical efficacy of corticosteroids and some anti-allergic drugs for treatment of chronic idiopathic urticaria.