Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?3. (10th May 2018)

• Record Type: Journal Article
• Authors: Kanni, T.; Zenker, O.; Habel, M.; Riedemann, N.; Giamarellos‐Bourboulis, E.J.
• Is Part Of: British journal of dermatology. Volume 179:Number 2(2018)
• Page Start: 413
• Page End: 419
• Publication Date: 2018-05-10
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.16428
• Languages: English
• ISSNs: 0007-0963

Abstract

Summary: Background: Despite the heavy purulence observed in hidradenitis suppurativa (HS), the kinetics of complement anaphylatoxins acting to prime chemotaxis of neutrophils has not been studied. Objectives: To explore complement activation in HS. Methods: Circulating concentrations of complement factor C5a, as well as of membrane attack complex C5b‐9, were determined in the plasma of 54 treatment‐naïve patients and of 14 healthy controls, as well as in the pus of seven patients. Results were correlated with Hurley stage and International Hidradenitis Suppurativa Severity Score. Peripheral blood mononuclear cells (PBMCs) were isolated from seven patients with Hurley stage III HS and seven healthy volunteers and stimulated in the presence of 25% of plasma for the production of tumour necrosis factor‐α (TNF‐α). Results: Circulating C5a and C5b‐9 were significantly greater in patient than in control plasma; however, concentrations in pus were very low. Circulating C5a levels exceeding 28 ng mL −1 were associated with a specificity > 90% with the occurrence of HS. Circulating levels of C5a and C5b‐9 were greater in patients with more severe HS. PBMCs of patients produced high concentrations of TNF‐α only when growth medium was enriched with patient plasma; this was reversed with the addition of the C5a blocker IFX‐1. Conclusions: Systemic complement activation occurs in HS and may be used as a surrogate biomarker of HS. C5a stimulates overproduction of TNF‐α and may be a future therapeutic target. Abstract : What's already known about this topic? Complement activation has not been studied in hidradenitis suppurativa (HS). What does this study add? Circulating C5a and C5b5‐9 are increased in HS. Consumption of circulating C5a is associated with disease severity. C5a primes the overproduction of tumour necrosis factor‐α by circulating mononuclear cells. What is the translational message? Inhibition of C5a may be a new treatment option in HS, based on an entirely new mode of action. C5a may be a new surrogate biomarker for HS. Linked Comment: Jemec. Br J Dermatol 2018;179 :251–252 . Plain language summary available online Respond to this article