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To the Editor: In a small study with 20 patients suffering from psoriatic arthritis, Hammamoto et al. have investigated TNF-α promoter polymorphisms and failed to confirm the previously published (Höhler et al., 1997Höhler T. Kruger A. Schneider P.M. et al.A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis.J Invest Dermatol. 1997; 109: 562-565Crossref PubMed Scopus (175) Google Scholar;Arias et al., 1997Arias A.I. Giles B. Eiermann T.H. Sterry W. Pandey J.P. TNF alpha gene polymorphism in psoriasis.Clin Exp Immunogenet. 1997; 14: 118-122PubMed Google Scholar) association of psoriatic arthritis and psoriasis with a G to A transition polymorphism (TNF238.A) in the TNF-α promoter region. This polymorphism has attracted particular interest as it seems to influence the transcription of the TNF-α gene and decreases the production of TNF-α in particular by T lymphocytes (Kaluza et al., 2000Kaluza K. Reuss E. Grossmann S. Schopf R.E. Galle P.R. Maerker-Hermann E. Höhler T. Influence of tumor necrosis factor-alpha (TNF-α) -promoter polymorphisms on transcriptional and in vitro TNF-α-production in patients with psoriatic arthritis and psoriasis.J Invest Dermatol. 2000; 114: 1180-1183Abstract Full Text Full Text PDF PubMed Scopus (193) Google Scholar). We have forwarded the hypothesis that this polymorphism could be an additional major histocompatibility complex (MHC) encoded susceptibility factor for the development of psoriasis favoring persistence of cutaneous skin infections, e.g. by streptococci. The TNF238A polymorphism is part of the ancestral haplotype B57.1 (TNF238.A-B57-Cw6) that has been linked to psoriasis. This is the most common haplotype in Western European Caucasians with the disease (Jenisch et al., 1999Jenisch S. Westphal E. Nair R.P. et al.Linkage disequilibrium analysis of familial psoriasis: identification of multiple disease associated MHC haplotypes.Tissue Antigens. 1999; 53: 135-146Crossref PubMed Scopus (50) Google Scholar). In addition, a number of other haplotypes have been associated with the occurrence of psoriasis, e.g. B13-Cw6, B8-Cw7, and B37-Cw6 (Jenisch et al., 1999Jenisch S. Westphal E. Nair R.P. et al.Linkage disequilibrium analysis of familial psoriasis: identification of multiple disease associated MHC haplotypes.Tissue Antigens. 1999; 53: 135-146Crossref PubMed Scopus (50) Google Scholar), the latter being the most common disease associated haplotype in Japan (Imanishi et al., 1992Imanishi T. Akaza T. Kimura A. Tokunaga K. Gojobori T. Allele and haplotype frequencies for HLA and complement loci in various ethnic groups.in: Tsuji K. Aizawa M. Sasazuki T. HLA 1991 Proceedings of the Eleventh International Histocompatibility Workshop and Conference. Vol. 1. Oxford Science Publications, Oxford1992: 1065-1220Google Scholar). The strong haplotype conservation within the MHC makes the investigation of TNF-α polymorphisms in conjunction with HLA-B and Cw-alleles mandatory. Unfortunately, Hamamoto et al. do not provide any data concerning HLA-B- and -Cw-allele haplotypes and frequencies in their psoriatic arthritis group. Considering the high frequency of the B37-Cw6 haplotype in Japanese psoriasis patients (Imanishi et al., 1992Imanishi T. Akaza T. Kimura A. Tokunaga K. Gojobori T. Allele and haplotype frequencies for HLA and complement loci in various ethnic groups.in: Tsuji K. Aizawa M. Sasazuki T. HLA 1991 Proceedings of the Eleventh International Histocompatibility Workshop and Conference. Vol. 1. Oxford Science Publications, Oxford1992: 1065-1220Google Scholar) it is not surprising that the authors do not find an association with the TNF238.A promoter variant, which is almost exclusively found on the B57-Cw6 haplotype. Nevertheless, the findings of this small study are interesting as they underline ethnic heterogeneity in the genetics of psoriasis. These results should be confirmed in a larger set of Japanese patients with psoriasis vulgaris and psoriatic arthritis including HLA-B and Cw alleles in the analysis. Very recent data byNair et al., 2000Nair R.P. Stuart P. Henseler T. et al.Localization of psoriasis-susceptibility locus PSORS1 to a 60-kb interval telomeric to HLA-C.Am J Hum Genet. 2000; 66: 1833-1844Abstract Full Text Full Text PDF PubMed Scopus (217) Google Scholar indicate that the MHC encoded PSORS1 susceptibility locus, which has been confirmed in a number of different studies, is located 100 kB telomeric to HLA-C. This group has identified a 60 kB fragment of the ancestral haplotype 57.1 that is shared by all identifiable risk haplotypes. Nevertheless the TNF238.2 polymorphism on the B57.1 haplotype could characterize psoriasis patients with a particular disease course or be related to an impaired clearance of skin infections with candida or steptococci, and thus predispose individuals to the development of psoriasis.