1. Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?
Theodora Kanni,1 Othmar Zenker,2 Maria Habel,2 Niels Riedemann, 2 Evangelos J. Giamarellos-Bourboulis1
14th Department of Internal Medicine, National and Kapodistrian University of Athens, Medical School, Greece,
2InflaRx, Jena, Germany
British Journal of Dermatology. DOI: /bjd.16428

2. Theodora Kanni,First author
Evangelos J. Giamarellos-Bourboulis, Senior author

3. Introduction: Background to study
Hidradenitis suppurativa (HS) is a chronic debilitating skin disorder affecting skin areas rich in apocrine glands. During each flare, the affected apocrine gland becomes an inflamed nodule that spontaneously ruptures with the release of pus.
We don’t know how neutrophils are recruited to produce pus. One hypothesis is that this process is mediated by anaphylatoxins produced during complement activation, namely C5a. Complement activation has never been studied in HS.

4. Objective
To explore the kinetics of circulating concentrations of anaphylatoxin C5a as well as of membrane attack complex C5b-9 in vivo in people with HS

5. Methods 54 treatment-naïve patients with HS and 14 healthy controls
Patients with neutropenia and HIV-1 infection were excluded
Disease severity was scored by Hurley classification and iHS4 score
Plasma C5a and C5b-9 were measured by enzyme immunoassays
Peripheral blood mononuclear cells (PBMCs) were also isolated from 7 patients and 7 controls; stimulated with heat-killed Staphycococcus aureus in the absence/presence of own plasma.

6. Results (1)
C5a and C5b-9 were higher in the plasma of patients than controls
C5a and C5b-9 were higher in the plasma of patients with Hurley I stage disease that Hurley II/III disease
C5a and C5b-9 were higher in the plasma of patients with mild disease than moderate/severe disease (iHS4 classification)
The odds ratio for HS when C5a was >28ng/ml was (95% confidence intervals: ; p: 0.005).

7. Figure One

8. Results (2)
PBMCs of patients produce less TNFα than controls after stimulation with S.aureus
PBMCs of patients become over-producers of TNFα upon addition of plasma in the growth medium
This plasma-associated over-production of TNFα is attenuated upon addition of IFX-1
IFX-1 is a chimeric monoclonal IgG4 kappa antibody which specifically binds to the soluble human complement split product C5a

9. Discussion (1)
Systemic activation of complement is observed in this cohort with HS
The concentrations of C5a and C5b-9 found in patients with HS are greater than the circulating concentrations described for other systemic inflammatory disorders including like multiple injuries and severe sepsis.
Complement activation supports a systemic inflammatory reaction as contributing to pathogenesis of HS.
Complement activation may happen early in disease process; complement levels were greater in Hurley I stage disease patients.

10. Discussion (2)
C5a is a host component mandatory for priming of the production of TNFα by human monocytes in HS
Blocking C5a may be a future therapeutic target for HS

11. Conclusions What does this study add?
Circulating C5a and C5b5-9 are increased in HS vs. controls
Consumption of circulating C5a is associated with disease severity
C5a primes the over-production of TNFα by circulating mononuclear cells

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