Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis

Lara Gibellini, Sara De Biasi, Elena Bianchini, Regina Bartolomeo, Antonella Fabiano, Marco Manfredini, Federica Ferrari, Giuseppe Albertini, Tommaso Trenti, Milena Nasi, Marcello Pinti, Anna Iannone, Carlo Salvarani, Andrea Cossarizza, Giovanni Pellacani

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Article numbere0167757
JournalPLoS One
Volume11
Issue number12
DOIs
Publication statusPublished - Dec 1 2016

Fingerprint

psoriasis
Psoriasis
monocytes
Monocytes
drugs
Pharmaceutical Preparations
Tumor Necrosis Factor Receptors
Anti-Idiotypic Antibodies
Antibodies
mononuclear leukocytes
antibodies
Blood
Blood Cells
receptors
Modulation
Drug Receptors
Plasmas
Phenotype
phenotype
Infliximab

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Gibellini, L., De Biasi, S., Bianchini, E., Bartolomeo, R., Fabiano, A., Manfredini, M., ... Pellacani, G. (2016). Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis. PLoS One, 11(12), [e0167757]. https://doi.org/10.1371/journal.pone.0167757

Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis. / 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.

In: PLoS One, Vol. 11, No. 12, e0167757, 01.12.2016.

Research output: Contribution to journalArticle

Gibellini, L, De Biasi, S, Bianchini, E, Bartolomeo, R, Fabiano, A, Manfredini, M, Ferrari, F, Albertini, G, Trenti, T, Nasi, M, Pinti, M, Iannone, A, Salvarani, C, Cossarizza, A & Pellacani, G 2016, 'Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis', PLoS One, vol. 11, no. 12, e0167757. https://doi.org/10.1371/journal.pone.0167757
Gibellini L, De Biasi S, Bianchini E, Bartolomeo R, Fabiano A, Manfredini M et al. Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis. PLoS One. 2016 Dec 1;11(12). e0167757. https://doi.org/10.1371/journal.pone.0167757
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. / Anti-TNF-α drugs differently affect the TNFα-sTNFR system and monocyte subsets in patients with psoriasis. In: PLoS One. 2016 ; Vol. 11, No. 12.
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