Epithelialized tunnels are a source of inflammation in hidradenitis suppurativa - 03/06/21
Abstract |
Background |
Hidradenitis suppurativa (HS), also known as acne inversa, is a chronic, painful, and burdensome inflammatory disease manifesting in nodules and abscesses, with progression to chronically draining tunnels in later-stage disease.
Objective |
We sought to determine whether HS tunnels are immunologically active participants in disease activity.
Methods |
Skin biopsy specimens were obtained by using ultrasound guidance in untreated patients with HS and those enrolled in an open-label study of brodalumab (ClinicalTrials.gov identifier NCT03960268) for patients with moderate-to-severe HS.
Results |
Immunohistochemistry of HS biopsy specimens demonstrated that the epithelialized HS tunnels recapitulate the psoriasiform epidermal hyperplasia morphology of the overlying epidermis, displaying molecular inflammation, including S100A7 (psoriasin) positivity, as well as features of epidermal skin, including loricrin, filaggrin, lipocalin-2, and Melan-A positive cells. Tunnels were associated with increased infiltration of T cells, dendritic cells, and neutrophils; formation of neutrophil extracellular traps, and increased expression of psoriasiform proinflammatory cytokines. Unsupervised hierarchical clustering demonstrated a separation of HS samples based on the presence or absence of tunnels. Tunnels isolated by microdissection had higher levels of epithelium-derived inflammatory cytokines compared with the overlying epidermis and healthy controls. Clinically, the size and draining of the tunnels were decreased with treatment with the IL-17RA antagonist brodalumab.
Conclusion |
These data suggest that tunnels are a source of inflammation in HS.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Hidradenitis suppurativa, IL-17, neutrophils, brodalumab
Abbreviations used : H&E, HS, IHC, IL-17RA, IPGM, NET, NL, RT, TLDA, TNF-α
Plan
| K.N. was supported by a Medical Scientist Training Program grant from the National Institute of General Medical Sciences of the National Institutes of Health under award number T32GM007739 to the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program. J.W.F. and J.G.K. were supported in part by grant UL1 TR001866 from the National Center for Advancing Translational Sciences, National Institutes of Health Clinical and Translational Science Award Program. J.W.F. was supported by the Shapiro-Silverberg Fund for the Advancement of Translational Research and the Hidradenitis Suppurativa Foundation Danby Grant. |
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| Disclosure of potential conflict of interest: J. G. Krueger has received research support (grants paid to his institution) from AbbVie, Amgen, BMS, Boehringer, EMD Serono, Innovaderm, Kineta, LEO Pharma, Novan, Novartis, Paraxel, Pfizer, Regeneron, and Vitae, as well as by personal fees from AbbVie, Acros, Allergan, Aurigne, BiogenIdec, Boehringer, Escalier, Janssen, Lilly, Novartis, Pfizer, Roche, and Valeant. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 147 - N° 6
P. 2213-2224 - juin 2021 Retour au numéro
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