Comparative Genetic Association of Human Leukocyte Antigen Class II and Tumor Necrosis Factor-Alpha with Dermatitis Herpetiformis

Abstract

Dermatitis herpetiformis is a chronic subepidermal vesicular autoimmune skin disease characterized by a strong association with the human leukocyte antigen A1-B8-DR3-DQ2 haplotype. Although the strongest major histocompatibility complex association has been shown to be with the DQw2 (DQB1*0201/DQA1*0501) heterodimer, recent evidence has suggested that there may be up to three susceptibility loci within the major histocompatibility complex. Tumor necrosis factor-alpha (TNF-alpha) is a cytokine with a broad range of proinflammatory, immunomodulating, and catabolic activities. We have recently described the first known polymorphism in the human TNF-alpha gene, which is biallelic and lies in the promoter region. The rare allele, TNF2, is in strong linkage disequilibrium with the human leukocyte antigen A1-B8-DR3-DQ2 haplotype. We therefore examined TNF-alpha genotypes in patients with dermatitis herpetiformis and controls and compared the association with that of the class II alleles. Although TNF2 is strongly associated with dermatitis herpetiformis, this was weaker than the association with the class II loci, with DQw2 (DQB1*0201/DQA1*0501) showing the strongest disease association. Of the four patients negative for this marker, only one carried the TNF2 allele. These results indicate that TNF2 is not a major disease susceptibility marker, although our results do not exclude a minor role.

Recovery of CD4+ T Cells in HIV Patients With a Stable Virologic Response to Antiretroviral Therapy Is Associated With Polymorphisms of Interleukin-6 and Central Major Histocompatibility Complex Genes

“…11 Alleles at CCR5D32, CCR5 59353, CCR2+190 (V64I), SDF1 3#UTR, and CCR5 59029 were determined by sequence-specific priming. 12 IL4-589 13 and TNFA-1031 14 alleles were assessed by PCR-RFLP using primers described previously.…”

TNF-? gene polymorphism: Clinical and biological implications

“…Small studies have been carried out in a variety of conditions. Disease associations have been shown for the TNF -308 alleles and dermatitis herpetiformis (Wilson et al, 1995a) or alopecia areata (Galbraith and Pandey, 1995). In three studies of various forms of psoriasis (Alheresh et al, 1997;Arias et al, 1997;Hohler et al, 1997) all showed significant associations with the TNF -238 alleles, and the latter study (Alheresh et al, 1997) also showed an association with TNF -308 polymorphism.…”

Haplotype structure of inflammatory cytokines genes (IL1B, IL6 and TNF/LTA) in US Caucasians and African Americans

“…28 In support for a clinical relevance, the À308A allele is associated with a seven-fold increased risk for cerebral complications of malaria 29 and with a worse prognosis and longer disease duration in dermatitis herpetiformis. 30 However, the same marker was not responsible for differential TNFa production induced by standard in vitro stimuli. 31 Although taking into consideration the importance and informativeness of known functional loci in inflammatory genes, it can be assumed that consistent pictures of IL1b, IL6 and TNF genotype-phenotype relationships are yet to emerge.…”