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Species: human
Number of cells: 23723
Number of downloads: 33
Study size: 620MB
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Hidradenitis suppurativa 
TNF-α blockade 
skin 

Immunopathogenesis of hidradenitis suppurativa and response to anti–TNF-α therapy

Margaret M. Lowe, Haley B. Naik, Sean Clancy, Mariela Pauli, Kathleen M. Smith, Yingtao Bi, Robert Dunstan, Johann E. Gudjonsson, Maia Paul, Hobart Harris, Esther Kim, Uk Sok Shin, Richard Ahn, Wilson Liao, Scott L. Hansen, and Michael D. Rosenblum

Hidradenitis suppurativa (HS) is a highly prevalent, morbid inflammatory skin disease with limited treatment options. The major cell types and inflammatory pathways in skin of patients with HS are poorly understood, and which patients will respond to TNF-α blockade is currently unknown. We discovered that clinically and histologically healthy appearing skin (i.e., nonlesional skin) is dysfunctional in patients with HS with a relative loss of immune regulatory pathways. HS skin lesions were characterized by quantitative and qualitative dysfunction of type 2 conventional dendritic cells, relatively reduced regulatory T cells, an influx of memory B cells, and a plasma cell/plasmablast infiltrate predominantly in end-stage fibrotic skin. At the molecular level, there was a relative bias toward the IL-1 pathway and type 1 T cell responses when compared with both healthy skin and psoriatic patient skin. Anti–TNF-α therapy markedly attenuated B cell activation with minimal effect on other inflammatory pathways. Finally, we identified an immune activation signature in skin before anti–TNF-α treatment that correlated with subsequent lack of response to this modality. Our results reveal the fundamental immunopathogenesis of HS and provide a molecular foundation for future studies focused on stratifying patients based on likelihood of clinical response to TNF-α blockade.

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