title: Differential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients.
abstract: Anti-tumour necrosis factor (TNF) biologics have revolutionized therapy of rheumatoid arthritis (RA). We compared the effects of infliximab on numbers of circulating leucocyte subsets in early RA (disease/symptom duration of ≤1 year) and late RA patients (>1 year). A control group consisted of early RA patients treated with a combination of methotrexate (MTX) and methylprednisolone. Blood samples were obtained at baseline (pre-therapy) from all RA patients, divided into three groups: (i) late RA receiving infliximab/MTX, (ii) early RA-infliximab/MTX, (iii) early RA-steroid/MTX, and also from follow-up patients at 2 and 14 weeks. Significant differences in absolute counts of monocytes and granulocytes were observed between healthy controls and RA patients. At baseline CD14(bright)  monocytes and CD16(+)  granulocytes were increased in both early RA and late RA patients. CD4(+)  T cells, CD8(+)  T cells and B cells were all increased at baseline in early RA, but not in late RA. At 2 weeks following infliximab treatment decreased granulocytes were observed in both early and late RA and decreased natural killer (NK) cells in late RA. CD16(+)  granulocytes and NK cells were also decreased at 14 weeks post-infliximab in early RA. Biotinylated infliximab was used to detect membrane-associated TNF (mTNF)-expressing leucocytes in RA patients. CD16(+)  granulocytes, NK cells and CD14(dim)  monocytes all expressed higher levels of mTNF in RA patients. In summary infliximab is associated with decreased CD16(+)  granulocyte and NK cell counts, possibly through binding of mTNF. Differential effects of infliximab between early and late RA suggest that pathogenic mechanisms change as disease progresses.
authors.affiliation: NIHR-Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Leeds, UK.
authors.forename: L R
authors.initials: LR
authors.lastname: Coulthard
authors.forename: J
authors.initials: J
authors.lastname: Geiler
authors.forename: R J
authors.initials: RJ
authors.lastname: Mathews
authors.forename: L D
authors.initials: LD
authors.lastname: Church
authors.forename: L J
authors.initials: LJ
authors.lastname: Dickie
authors.forename: D L
authors.initials: DL
authors.lastname: Cooper
authors.forename: C
authors.initials: C
authors.lastname: Wong
authors.forename: S
authors.initials: S
authors.lastname: Savic
authors.forename: D
authors.initials: D
authors.lastname: Bryer
authors.forename: M H
authors.initials: MH
authors.lastname: Buch
authors.forename: P
authors.initials: P
authors.lastname: Emery
authors.forename: A W
authors.initials: AW
authors.lastname: Morgan
authors.forename: M F
authors.initials: MF
authors.lastname: McDermott
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology / Q000628:therapy*; D001402:B-Lymphocytes / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D016022:Case-Control Studies; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000378:metabolism; D006098:Granulocytes / Q000187:drug effects; D006801:Humans; D000069285:Infliximab; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects*; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage; D008775:Methylprednisolone / Q000627:therapeutic use; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D017452:Receptors, IgG / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D008775:Methylprednisolone; D008727:Methotrexate