Analysis of FcαRI rs16986050 polymorphism in relation to autoimmune responses in dermatitis herpetiformis: an issue probing study

Dermatitis herpetiformis (DH) is an autoimmune blistering dermatosis (ABD) associated with gluten intolerance [1, 2]. It is postulated that DH is a blistering skin manifestation of gluten-sensitive enteropathy (celiac disease). However, the precise molecular relationship is still not fully understand. The presence of various proteins (epidermal transglutaminase – eTG, tissue transglutaminase – tTG, nonapeptides of gliadin – npG) and the lack of precise identification of a specific individual molecule [3] suggests that DH is unlikely to be a classical autoantigen-driven autoimmune disease. Thus, specific genetic susceptibility, as well as environmental factors, is implicated in DH induction and progression. The involvement of the impaired human immunoglobulin A (IgA) Fc receptor (FcRs) regulatory system is proposed, which may be linked to the activation of disease. The affinity of IgA Fc receptors (FcRs) to the autoimmune response in DH may vary based on single-nucleotide polymorphisms (SNPs) influencing the course and severity of the disease. Based on our previous studies [3, 4] FcI/CD89 seems to be the most promising candidate associated with the immune response during DH development. FcI/CD89 is a transmembrane glycoprotein binding both IgA1 and IgA2. CD89 shows abundant expression on human neutrophils and mediates inflammatory responses to IgA-immunocomplexes. The functional polymorphism 844 A>G in FCAR/CD89 (rs16986050) is associated with a proinflammatory response, and with a higher percentage of cells with the formation of neutrophil extracellular trap (NET) [5]. However, there seem to be no data or consensus concerning FCAR/CD89 polymorphisms in DH.