Anti-TNF-α Drugs Differently Affect the TNFα-sTNFR System and Monocyte Subsets in Patients with Psoriasis

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-T...

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Published in:	PloS one 2016-12, Vol.11 (12), p.e0167757-e0167757
Main Authors:	Gibellini, Lara, De Biasi, Sara, Bianchini, Elena, Bartolomeo, Regina, Fabiano, Antonella, Manfredini, Marco, Ferrari, Federica, Albertini, Giuseppe, Trenti, Tommaso, Nasi, Milena, Pinti, Marcello, Iannone, Anna, Salvarani, Carlo, Cossarizza, Andrea, Pellacani, Giovanni
Format:	Article
Language:	eng
Subjects:	Adalimumab - immunology Adalimumab - therapeutic use Adult Aged Amino acids Anti-Inflammatory Agents - immunology Anti-Inflammatory Agents - therapeutic use Antibodies Antibodies - blood Antibodies - immunology Biology and Life Sciences Cell adhesion & migration Cohort Studies Cytokines Dendritic cells Dentistry Dermatologic Agents - immunology Dermatologic Agents - therapeutic use Dermatology Drug dosages Drugs Etanercept Etanercept - immunology Etanercept - therapeutic use Female Humans Immunoglobulins Inflammation Infliximab Infliximab - immunology Infliximab - therapeutic use Leukocytes (mononuclear) Leukocytes, Mononuclear - drug effects Leukocytes, Mononuclear - immunology Life sciences Lymphocytes Male Medicine Medicine and Health Sciences Middle Aged Modulation Monoclonal antibodies Monocytes Monocytes - drug effects Monocytes - immunology Morphology Pathogenesis Patients Peripheral blood mononuclear cells Plaques Plasma levels Psoriasis Psoriasis - blood Psoriasis - drug therapy Psoriasis - immunology Receptors Receptors, Tumor Necrosis Factor - blood Receptors, Tumor Necrosis Factor - immunology Research and Analysis Methods Rheumatoid arthritis Serum levels Surgery Systematic review TNF inhibitors Tumor Necrosis Factor-alpha - antagonists & inhibitors Tumor Necrosis Factor-alpha - blood Tumor Necrosis Factor-alpha - immunology Tumor necrosis factor-TNF Tumor necrosis factor-α
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Summary:	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.
ISSN:	1932-6203 1932-6203