Paradoxical psoriasis induced by TNF-α blockade shows immunological features typical of the early phase of psoriasis development.
anti-TNF-α therapy
hidradenitis suppurativa
innate immunity
lymphotoxin
paradoxical psoriasis
psoriasis
skin inflammation
type I IFN
Journal
The journal of pathology. Clinical research
ISSN: 2056-4538
Titre abrégé: J Pathol Clin Res
Pays: England
ID NLM: 101658534
Informations de publication
Date de publication:
01 2020
01 2020
Historique:
received:
22
08
2019
revised:
17
09
2019
accepted:
19
09
2019
pubmed:
3
10
2019
medline:
23
6
2021
entrez:
3
10
2019
Statut:
ppublish
Résumé
Immunomodulation with anti-TNF-α is highly effective in the treatment of various immune-mediated inflammatory diseases, including hidradenitis suppurativa (HS). However, this may be responsible for unexpected paradoxical psoriasiform reactions. The pathogenic mechanisms underlying the induction of these events are not clear, even though the involvement of innate immune responses driven by plasmacytoid dendritic cells (pDC) has been described. In addition, the genetic predisposition to psoriasis of patients could be determinant. In this study, we investigated the immunological and genetic profiles of three HS patients without psoriasis who developed paradoxical psoriasiform reactions following anti-TNF-α therapy with adalimumab. We found that paradoxical psoriasiform skin reactions show immunological features common to the early phases of psoriasis development, characterized by cellular players of innate immunity, such as 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, other innate immunity molecules, such as the catheledicin LL37 and lymphotoxin (LT)-α and LT-β were overproduced. Interestingly, these innate immunity molecules were abundantly expressed by keratinocytes, in addition to the inflammatory infiltrate. In contrast to classical psoriasis, psoriasiform lesions of HS patients showed a reduced number of IFN-γ and TNF-α-releasing T lymphocytes. On the contrary, IL-22 immunoreactivity was significantly augmented together with the IL-36γ staining in leukocytes infiltrating the dermis. Finally, we found that all HS patients with paradoxical reactions carried allelic variants in genes predisposing to psoriasis. Among them, SNPs in ERAP1, NFKBIZ, and TNFAIP genes and in the HLA-C genomic region were found.
Identifiants
pubmed: 31577850
doi: 10.1002/cjp2.147
pmc: PMC6966707
doi:
Substances chimiques
Anti-Inflammatory Agents
0
TNF protein, human
0
Tumor Necrosis Factor-alpha
0
Adalimumab
FYS6T7F842
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
55-68Informations de copyright
© 2019 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
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