Role of the Complement Pathway in Inflammatory Skin Diseases: A Focus on Hidradenitis Suppurativa

Abstract

Although the role of immune dysregulation in hidradenitis suppurativa (HS) has yet to be elucidated, recent studies identified several complement abnormalities in patients with HS. The complement system serves a critical role in the modulation of immune response and regulation of cutaneous commensal bacteria. Complement is implicated in several inflammatory skin diseases including systemic lupus erythematosus, angioedema, pemphigus, bullous pemphigoid, and HS. A model of HS pathogenesis is proposed, integrating the role of commensal bacteria, cutaneous immune responses, and complement dysregulation. The role of complement in disease pathogenesis has led to the development of novel anticomplement agents and clinical trials investigating the efficacy of such treatments in HS.

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

“…The inflammatory signature of established hidradenitis suppurativa has been well characterized in multiple histologic 26,41 and molecular studies. 26,[42][43][44][45] Similarities and parallels with psoriasis 26 have been observed in lesional and perilesional hidradenitis suppurativa tissue, 26,46 with lesional nodules demonstrating mixed inflammatory infiltrates comprising T cells, dendritic cells, plasma cells, neutrophils, [47][48][49][50] and monocytes. 51 Chronic long-…”

What causes hidradenitis suppurativa ?—15 years after

“…Complement split products, like complement 5a (C5a), mediate neutrophil chemotaxis and may play some role in HS pathogenesis. 79,80 Indeed, C1q, C2 and factor B were found to be up-regulated and factor H, factor D and C7 downregulated in HS. In recent months, we have witnessed the spread of the novel coronavirus, SARS-CoV-2, which resulted in a global health emergency.…”

A Systematic Review of Promising Therapeutic Targets in Hidradenitis Suppurativa: A Critical Evaluation of Mechanistic and Clinical Relevance

“…The localization of complements (especially C5a) has not been assessed in HS tissue. Evidence from other inflammatory disorders identifies complement receptors as present on neutrophils, DCs, and monocytes (reviewed in [Ghias et al, 2020;Grand et al, 2020]). In vitro functional studies with anticomplement agents are limited.…”