Neutrophil extracellular traps, B cells, and type I interferons contribute to immune dysregulation in hidradenitis suppurativa

Angel S. Byrd, Carmelo Carmona-Rivera, Liam J. O'Neil, Philip M. Carlucci, Cecilia Cisar, Avi Rosenberg, Michelle L. Kerns, Julie Caffrey, Stephen M. Milner, Justin Michael Sacks, Oluseyi Aliu, Kristen Broderick, Jonathan S. Reichner, Lloyd S Miller, Sewon Kang, William H. Robinson, Ginette A. Okoye, Mariana J. Kaplan

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Abstract

Hidradenitis suppurativa (HS), also known as acne inversa, is an incapacitating skin disorder of unknown etiology manifested as abscess-like nodules and boils resulting in fistulas and tissue scarring as it progresses. Given that neutrophils are the predominant leukocyte infiltrate in HS lesions, the role of neutrophil extracellular traps (NETs) in the induction of local and systemic immune dysregulation in this disease was examined. Immunofluorescence microscopy was performed in HS lesions and detected the prominent presence of NETs. NET complexes correlated with disease severity, as measured by Hurley staging. Neutrophils from the peripheral blood of patients with HS peripheral also displayed enhanced spontaneous NET formation when compared to healthy control neutrophils. Sera from patients recognized antigens present in NETs and harbored increased antibodies reactive to citrullinated peptides. B cell dysregulation, as evidenced by elevated plasma cells and IgG, was observed in the circulation and skin from patients with HS. Peptidylarginine deiminases (PADs) 1 to 4, enzymes involved in citrullination, were differentially expressed in HS skin, when compared to controls, in association with enhanced tissue citrullination. NETs in HS skin coexisted with plasmacytoid dendritic cells, in association with a type I interferon (IFN) gene signature. Enhanced NET formation and immune responses to neutrophil and NET-related antigens may promote immune dysregulation and contribute to inflammation. This, along with evidence of up-regulation of the type I IFN pathway in HS skin, suggests that the innate immune system may play important pathogenic roles in this disease.

Original languageEnglish (US)
Article numberaav5908
JournalScience translational medicine
Volume11
Issue number508
DOIs
StatePublished - Sep 4 2019

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ASJC Scopus subject areas

  • Medicine(all)

Cite this

Byrd, A. S., Carmona-Rivera, C., O'Neil, L. J., Carlucci, P. M., Cisar, C., Rosenberg, A., Kerns, M. L., Caffrey, J., Milner, S. M., Sacks, J. M., Aliu, O., Broderick, K., Reichner, J. S., Miller, L. S., Kang, S., Robinson, W. H., Okoye, G. A., & Kaplan, M. J. (2019). Neutrophil extracellular traps, B cells, and type I interferons contribute to immune dysregulation in hidradenitis suppurativa. Science translational medicine, 11(508), [aav5908]. https://doi.org/10.1126/scitranslmed.aav5908