Experimental Methods for the Immunological Characterization of Paradoxical Psoriasis Reactions Induced by TNF-α Biologics

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Immunomodulation with anti-TNFα biologics is highly effective in the treatment of various immune-mediated inflammatory diseases, even though 2–5% of patients treated can develop paradoxical psoriasiform skin lesions. We recently analyzed three patients affected by severe hidradenite suppurativa (HS), and who developed paradoxical psoriasiform reactions following treatment with the TNF-α blockers. Psoriasiform skin reactions showed immunological and immunohistochemical features common to acute psoriasis, characterized by cellular players of innate immunity, such as plasmacytoid dendritic cells (pDC), neutrophils, mast cells, macrophages, and monocytes. In addition, IFN-β and IFN-α2a, two type I IFNs typical of early psoriasis, were highly expressed in paradoxical skin reactions. Concomitantly, the lymphotoxin (LT)-α and LT-β were overproduced. Detection of innate immunity cells was carried out on skin sections from HS patients, by immunohistochemistry (IHC) by using antibodies (Abs) against markers identifying specific leukocyte subpopulations. Anti-BDCA2, anti-CD15, anti-CD117, anti-CD68, anti-CD11c, and anti-CD3 Abs were employed to detect pDC, neutrophils, mast cells, macrophages, monocytes/dendritic cells, and T lymphocytes, respectively. In parallel, skin expression of the innate immunity soluble mediators IL-36γ, IFN-β, IFN-κ, LT-α and LT-β was also evaluated by IHC by using specific Abs. In this chapter, we describe the methods and protocols to detect the in situ expression and localization of innate immunity molecules and leukocyte subpopulations in skin lesions where inflammatory and psoriasiform reactions are evoked by anti-TNF- α biological therapy.

Original languageEnglish
Title of host publicationMethods in Molecular Biology
PublisherHumana Press Inc.
Pages155-165
Number of pages11
DOIs
Publication statusPublished - 2021

Publication series

NameMethods in Molecular Biology
Volume2248
ISSN (Print)1064-3745
ISSN (Electronic)1940-6029

Keywords

  • IL-17A
  • Innate immunity
  • Lymphotoxins
  • Paradoxical psoriasis
  • Plasmacytoid dendritic cells
  • TNF-α blockade
  • Type I IFNs

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics

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