{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T15:10:53Z","timestamp":1793459453410,"version":"4.5.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2019,10,29]],"date-time":"2019-10-29T00:00:00Z","timestamp":1572307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology CR"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Immunomodulation with anti\u2010TNF\u2010\u03b1 is highly effective in the treatment of various immune\u2010mediated 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\u2010TNF\u2010\u03b1 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\u2010\u03b2 and IFN\u2010\u03b12a, 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)\u2010\u03b1 and LT\u2010\u03b2 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\u2010\u03b3 and TNF\u2010\u03b1\u2010releasing T lymphocytes. On the contrary, IL\u201022 immunoreactivity was significantly augmented together with the IL\u201036\u03b3 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 <jats:italic>ERAP1<\/jats:italic>, <jats:italic>NFKBIZ<\/jats:italic>, and <jats:italic>TNFAIP<\/jats:italic> genes and in the <jats:italic>HLA\u2010C<\/jats:italic> genomic region were found.<\/jats:p>","DOI":"10.1002\/cjp2.147","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T12:40:18Z","timestamp":1570020018000},"page":"55-68","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Paradoxical psoriasis induced by TNF\u2010\u03b1 blockade shows immunological features typical of the early phase of psoriasis development"],"prefix":"10.1002","volume":"6","author":[{"given":"Luca","family":"Fania","sequence":"first","affiliation":[{"name":"Laboratory of Experimental Immunology and 1st Dermatology Division IDI\u2010IRCCS  Rome 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