POLYMORPHISM OF THE TUMOR-NECROSIS-FACTOR GENES IN PATIENTS WITH DERMATITIS-HERPETIFORMIS

In 18 patients with dermatitis herpetiformis (DH) of whom 16 were HLA- DR3 positive and 14 had the HLA-B8, -DR3 haplotype, the frequencies of known mutations of the tumor necrosis factor alpha (TNF-alpha) and TN F-beta genes were investigated using restriction fragment length polym orphism analysis and the single-strand conformational polymorphism tec hnique. In DH, the phenotype frequency (28%) and allele frequency (0.5 8) of the rare TNF-beta allele TNFB1 were significantly increased (no rmal control 12.4% and 0.37). For the TNF-alpha promoter/enhancer poly morphism, the rare allele TNF2 was more frequent in DH patients (11%, 0.47) compared to controls (2%, 0.16). Since functional studies have a ssociated the rare TNFB1 and TNF2 alleles with a higher secretion of TNF upon activation in vitro, the predominance of these two 'high-resp onse' TNF alleles in DH patients may represent a genetic basis for the chronic inflammatory response in the skin and mucosal tissues of pati ents with DH.