title: Relation among anti-rheumatic drug therapy, CD14(+)CD16(+) blood monocytes and disease activity markers (DAS28 and US7 scores) in rheumatoid arthritis: A pilot study.
abstract: Circulating human monocytes, a functionally and phenotypically heterogeneous population, are emerging as fundamental cell types in rheumatoid arthritis (RA). The aim of this pilot study was to assess the correlation, if any, among anti-rheumatic drug therapy, circulating CD14(+)CD16(+) monocytes and validated clinical scales (e.g., DAS28 score and ultrasonography US7 score) of disease severity in RA. Thirty consecutive RA patients, either naïve or under disease-modifying anti-rheumatic drugs (DMARDs) or biological therapy, and 10 age-matched healthy volunteers, were enrolled. Monocytes were prepared from heparinized blood samples; surface expression of CD14 and CD16 was determined by flow cytometry. RA patients presented a significantly higher percentage of CD14(+)CD16(+) monocytes, as compared to healthy subjects. There was a good correlation between DAS28 clinical score and the ultrasound composite score US7 (r=0.66), as well as between both scores and the percentage of CD14(+)CD16(+) monocytes (r=0.43 and 0.47, respectively). Naïve RA patients had the highest expression (19.2±3.2%) of CD14(+)CD16(+) monocytes and elevated DAS28 score; patients on DMARDs presented a 7-fold increased expression of CD14(+)CD16(+) monocytes, relatively to healthy volunteers (2.1±1.4%), and an intermediate disease severity. The RA patients treated with biological therapy had a low percentage of CD14(+)CD16(+) monocytes (5.1±3.6%; p<0.01 vs naïve and DMARDs groups), similar to the one detected in healthy controls, and reduced US7 and DAS28 scores. Interestingly, for the same DAS28 score, monocytes isolated from RA patients on biological therapy had a lower CD16 expression than patients on DMARDs. Therefore, CD14(+)CD16(+) circulating blood monocytes may represent an appropriate biomarker to assess RA disease activity along with DAS28 and US7 scores. Together, these three parameters may represent a better indicator for evaluating therapy efficacy.
authors.affiliation: Department of Health Sciences, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoruso
authors.affiliation: Department of Health Sciences, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy; Azienda Ospedaliera Universitaria ⿿Maggiore della Carità⿿, 28100 Novara, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Sola
authors.affiliation: Azienda Ospedaliera Universitaria ⿿Maggiore della Carità⿿, 28100 Novara, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Rossi
authors.affiliation: Department of Health Sciences, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy.
authors.forename: Joyce Afrakoma
authors.initials: JA
authors.lastname: Obeng
authors.affiliation: Department of Health Sciences, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy.
authors.forename: Luigia Grazia
authors.initials: LG
authors.lastname: Fresu
authors.affiliation: Azienda Ospedaliera Universitaria ⿿Maggiore della Carità⿿, 28100 Novara, Italy; IRCAD, School of Medicine, Novara, Italy.
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Sainaghi
authors.affiliation: Azienda Ospedaliera Universitaria ⿿Maggiore della Carità⿿, 28100 Novara, Italy; IRCAD, School of Medicine, Novara, Italy; Department of Translational Medicine, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Pirisi
authors.affiliation: Department of Health Sciences, School of Medicine, University of Eastern Piedmont, Via Solaroli, 17-28100 Novara, Italy; IRCAD, School of Medicine, Novara, Italy. Electronic address: sandra.brunelleschi@med.uniupo.it.
authors.forename: Sandra
authors.initials: S
authors.lastname: Brunelleschi
mesh_terms: D000328:Adult; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000276:immunology; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000276:immunology*; D008297:Male; D008727:Methotrexate / Q000494:pharmacology / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D010865:Pilot Projects; D011241:Prednisone / Q000494:pharmacology / Q000627:therapeutic use; D017452:Receptors, IgG / Q000276:immunology*; D012720:Severity of Illness Index
chemical_list: D000906:Antibodies; D018501:Antirheumatic Agents; D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D011241:Prednisone; D008727:Methotrexate
keywords: Biological drugs; CD14(+)CD16(+) monocytes; DAS28 score; DMARDs; Rheumatoid arthritis; US7 score