Immunology and genetics of tumour necrosis factor in allergic contact dermatitis

Abstract

During the sensitization phase of allergic contact dermatitis, the proinflammatory cytokine tumour necrosis factor (TNF) plays an important role by promoting epidermal Langerhans cell migration to draining lymph nodes. It also plays a role during the elicitation phase. The TNF gene (TNF) is located within the major histocompatibility complex region. Many single-nucleotide variants exist in the promoter region of TNF, and these may either increase or decrease mRNA transcription and therefore lead to higher or lower levels of TNF. The most extensively studied single-nucleotide variant of TNF is a base pair substitution in the promoter region at location –308 relative to the transcription start site (rs1800629, TNF –308G>A), which is believed to increase transcription and lead to higher TNF levels. The role of TNF in allergic contact dermatitis and the functionality of TNF –308G>A are reviewed in this article. The association between genetic variants and disease can be studied in a case–control design. Only a few case–control studies investigating the association between TNF –308G>A and allergic contact dermatitis have been published, with contradictory results. These are reviewed critically, and suggestions for future case–control studies on this topic are made.