Abstract
TNF-α has a central role in the development and maintenance of psoriatic plaques, and its serum levels correlate with disease activity. Anti-TNF-α drugs are, however, ineffective in a relevant percentage of patients for reasons that are currently unknown. To understand whether the response to anti-TNF-α drugs is influenced by the production of anti-drug antibodies or by the modulation of the TNFα-TNFα receptor system, and to identify changes in monocyte phenotype and activity, we analysed 119 psoriatic patients who either responded or did not respond to different anti-TNF-α therapies (adalimumab, etanercept or infliximab), and measured plasma levels of TNF-α, TNF-α soluble receptors, drug and anti-drug antibodies. Moreover, we analyzed the production of TNF-α and TNF-α soluble receptors by peripheral blood mononuclear cells (PBMCs), and characterized different monocyte populations. We found that: i) the drug levels varied between responders and non-responders; ii) anti-infliximab antibodies were present in 15% of infliximab-treated patients, while anti-etanercept or anti-adalimumab antibodies were never detected; iii) plasma TNF-α levels were higher in patients treated with etanercept compared to patients treated with adalimumab or infliximab; iv) PBMCs from patients responding to adalimumab and etanercept produced more TNF-α and sTNFRII in vitro than patients responding to infliximab; v) PBMCs from patients not responding to infliximab produce higher levels of TNF-α and sTNFRII than patients responding to infliximab; vi) anti- TNF-α drugs significantly altered monocyte subsets. A complex remodelling of the TNFα-TNFα receptor system thus takes place in patients treated with anti-TNF-α drugs, that involves either the production of anti-drug antibodies or the modulation of monocyte phenotype or inflammatory activity.
Highlights
Psoriasis, defined as plaque psoriasis or psoriasis vulgaris, is a chronic inflammatory disease characterized by the infiltration of inflammatory cells in the skin and hyper-proliferation of keratinocytes, resulting in red-coloured plaques, mainly located on elbows, knees, scalp and in the sacral area [1,2,3]
Among patients treated with adalimumab, 30 were R (62.5%) and 18 were NR (37.5%); among patients treated with etanercept, 20 were R (66.7%) and 10 were NR (33.3%); among patients treated with infliximab, 29 were R (70.8%) and 12 were NR (29.2%)
In patients treated with infliximab, the mean concentration of the drug was 2.63 μg mL-1 in R, and 1.63 μg mL-1 in NR, and no significant differences were observed between R and NR (Fig 1C)
Summary
Defined as plaque psoriasis or psoriasis vulgaris, is a chronic inflammatory disease characterized by the infiltration of inflammatory cells in the skin and hyper-proliferation of keratinocytes, resulting in red-coloured plaques, mainly located on elbows, knees, scalp and in the sacral area [1,2,3]. Myeloid DCs sustain the activation and differentiation of several T cell subsets, including type helper T cells (Th1), type-17 helper T cells (Th17), and γδ T cells These cells secrete a number of specific cytokines, including tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1, IL-6, IL-17A, IL-17F and IL-22, which play a role in the pathogenesis of psoriasis [3, 8]. TNF-α modulates the activity of various cells It induces the maturation of DCs, and skews monocyte differentiation from macrophages to DCs, favouring adaptive immunity [10]. It promotes the expression of adhesion molecules, including intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin, on dermal vascular endothelial cells. It induces the expression of chemokines, such as chemokine ligand (CCL)-20, CCL5, and CCL2 on keratinocytes and dermal fibroblasts [11]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
