Beyond antibodies: B cells in Hidradenitis Suppurativa: Bystanders, contributors or therapeutic targets?

Abstract

Hidradenitis Suppurativa (HS) is a chronic inflammatory dermatosis in which B cells play a prominent but unclear role. Our understanding of the role of B cells in innate and adaptive immunity (including antibody production, antigen presentation and effector functions) is rapidly evolving; and these novel findings require integration into the pathophysiologic model of HS. B cells are transiently present in normal human skin and have functions in the maintenance of innate cutaneous immunity. Recruitment and trafficking of B cells in significant numbers to skin is mediated via B cell-specific chemokines as well as shared signalling with T-cells. The evidence suggests that the presence of antibody-secreting B cells is not sufficient to induce clinical disease and

Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

“…However, to date no product has been definitively identified as an autoimmune target for the disease. 83 B cells are present in other chronic inflammatory disorders without known Initiating factors in hidradenitis suppurativa. Normal control skin (first panel from the left) from hidradenitis suppurativaeassociated cutaneous sites (eg, axilla) have normal colonizing microbionts (including within the follicular infundibulum), which are continuously monitored by circulating immune cells in homeostasis (circulating to and from regional lymph nodes (inset in first panel from the left).…”

“…Byrd et al 3 demonstrated that antibodies to citrullinated peptides contribute to the development of neutrophil extracellular traps in advanced disease, with parallels to B-cell and neutrophil extracellular traps in rheumatoid arthritis. 3 Case reports of rituximab ameliorating hidradenitis suppurativa disease activity are known, 83 but overall, the role of B cells as bystanders, amplifiers of existing inflammation, or central pathogenic players is unclear and requires further investigation. 83 The inflammatory infiltrate is associated with high levels of matrix metalloproteinases, which degrade the reticular lamina.…”

“…3 Case reports of rituximab ameliorating hidradenitis suppurativa disease activity are known, 83 but overall, the role of B cells as bystanders, amplifiers of existing inflammation, or central pathogenic players is unclear and requires further investigation. 83 The inflammatory infiltrate is associated with high levels of matrix metalloproteinases, which degrade the reticular lamina. Keratinocyte-leucocyte cross talk activated epithelial-mesenchyme-transition mechanisms, leading to degradation of the basement membrane zone, loss of hemidesmosomes and desmosomes, and keratinocytes expressing mesenchymal cell surface markers (yellow keratinocytes).…”

“… 2 , 11 The role and characteristics of B cells in mild to moderate hidradenitis suppurativa are unclear. 83 The presence of B cells and plasma cells in skin and blood 3 , 12 , 13 suggests the possibility that some component of severe or long-standing hidradenitis suppurativa may be an autoimmune or antibody-mediated disorder. However, to date no product has been definitively identified as an autoimmune target for the disease.…”

“…However, to date no product has been definitively identified as an autoimmune target for the disease. 83 B cells are present in other chronic inflammatory disorders without known autoimmune targets, including psoriasis and atopic dermatitis. 84 In these conditions, they are thought to be bystanders (secondary to combined B-cell and T-cell chemoattractants such as CXCL13 or CCL20) or secondary amplifiers of T-cell–mediated inflammation.…”