Psoriasis: Classical vs. Paradoxical. The Yin-Yang of TNF and Type I Interferon

Abstract

Chronic plaque psoriasis is a common debilitating skin disease. The identification of the pathogenic role of the TNF/IL-23/TH17 pathway has enabled the development of targeted therapies used in the clinic today. Particularly, TNF inhibitors have become a benchmark for the treatment of numerous chronic inflammatory diseases such as psoriasis. Although being highly effective in psoriasis treatment, anti-TNFs can themselves induce psoriasis-like skin lesions, a side effect called paradoxical psoriasis. In this review, we provide a comprehensive look at the different cellular and molecular players involved in classical plaque psoriasis and contrast its pathogenesis to paradoxical psoriasis, which is clinically similar but immunologically distinct. Classical psoriasis is a T-cell mediated autoimmune disease driven by TNF, characterised by T-cells memory, and a relapsing disease course. In contrast, paradoxical psoriasis is caused by the absence of TNF and represents an ongoing type-I interferon-driven innate inflammation that fails to elicit T-cell autoimmunity and lacks memory T cell-mediated relapses.

Apoptotic or Antiproliferative Activity of Natural Products against Keratinocytes for the Treatment of Psoriasis

“…The activated neutrophils are recruited into the stratum corneum in the early stage and they create focal aggregates, called Munro’s microabscesses [31]. The enhancement of TNF-α and IL-17 signaling in the psoriatic plaque drives the neutrophil accumulation into the inflamed skin area, activating keratinocytes to release chemokine (C-X-C motif) ligand (CXCL)1, CXCL2, CXCL3, CXCL5, and IL-8 [32]. In turn, neutrophils produce reactive oxygen species (ROS), IL-17, cathelicidin, and neutrophil extracellular traps (NETs) as proinflammatory signals to reduce the inflammation.…”

Janus kinase inhibitors in immuno-inflammatory rheumatic diseases: new opportunities and prospects

“…С этим может быть связана недостаточная эффективность терапии или развитие НЛР, в том числе «парадоксальных», на фоне лечения ГИБП. В качестве примера можно привести осложнение фармакотерапии ингибиторами ФНОα, определяющееся как «парадоксальный» псориаз, связанный, как полагают, с активацией ИФН-зависимого врожденного иммунного ответа, на фоне блокирования физиологических иммунорегуляторных эффектов ФНОα [102,103]. Следует принимать во внимание и иммуногенность ГИБП, индуцирующих синтез антилекарственных антител, которые могут приводить к «вторичной» неэффективности ГИБП [104].…”

Possible Paradoxical Photosensitive Psoriasis Induced by Tumour Necrosis Factor-alpha Inhibitors

“…The pathogenesis of this reaction remains unclear. It has been suggested that interferon-α overproduction by plasmacytoid dendritic cells, increased number of interleukin (IL)-17/IL-22 secreting Th17 cells and IFNsecreting Th1 cells may play a crucial role (4,5).…”