title: Anti-TNF-α Drugs Differently Affect the TNFα-sTNFR System and Monocyte Subsets in Patients with Psoriasis.
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.
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Lara
authors.initials: L
authors.lastname: Gibellini
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: De Biasi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Bianchini
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Regina
authors.initials: R
authors.lastname: Bartolomeo
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Fabiano
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Manfredini
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Ferrari
authors.affiliation: Dermatologic Unit, IRCCS - Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Albertini
authors.affiliation: Department of Clinical Pathology - NOCSAE Baggiovara, Modena, Italy.
authors.forename: Tommaso
authors.initials: T
authors.lastname: Trenti
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Milena
authors.initials: M
authors.lastname: Nasi
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Marcello
authors.initials: M
authors.lastname: Pinti
authors.affiliation: Department of Diagnostics, Clinical and Public Health Medicine, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Iannone
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.|Reumatology Unit, IRCCS - Santa Maria Nuova Hospital, Reggio Emilia, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Salvarani
authors.affiliation: Department of Medical and Surgical Sciences for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Andrea
authors.identifier: http://orcid.org/0000-0002-5381-1558
authors.initials: A
authors.lastname: Cossarizza
authors.affiliation: Department of Surgery, Medicine, Dentistry and Morphological Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pellacani
mesh_terms: D000068879:Adalimumab / Q000276:immunology / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000276:immunology / Q000627:therapeutic use*; D000906:Antibodies / Q000097:blood / Q000276:immunology; D015331:Cohort Studies; D003879:Dermatologic Agents / Q000276:immunology / Q000627:therapeutic use*; D000068800:Etanercept / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000069285:Infliximab / Q000276:immunology / Q000627:therapeutic use*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011565:Psoriasis / Q000097:blood / Q000188:drug therapy* / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D000906:Antibodies; D003879:Dermatologic Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068879:Adalimumab; D000068800:Etanercept