Differential effects of infliximab on absolute circulating blood leucocyte counts of innate immune cells in early and late rheumatoid arthritis patients

L R Coulthard, J Geiler, R J Mathews, L D Church, L J Dickie, D L Cooper, C Wong, S Savic, D Bryer, M H Buch, P Emery, A W Morgan, M F McDermott

    Research output: Contribution to journalArticlepeer-review

    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.

    Original languageEnglish
    Pages (from-to)36-46
    Number of pages11
    JournalClinical and experimental immunology
    Volume170
    Issue number1
    DOIs
    Publication statusPublished - Oct 2012

    Keywords

    • Adult
    • Aged
    • Antibodies, Monoclonal/administration & dosage
    • Antirheumatic Agents/therapeutic use
    • Arthritis, Rheumatoid/immunology
    • B-Lymphocytes/drug effects
    • CD4-Positive T-Lymphocytes/drug effects
    • CD8-Positive T-Lymphocytes/drug effects
    • Case-Control Studies
    • Disease Progression
    • Drug Therapy, Combination
    • Female
    • Flow Cytometry
    • GPI-Linked Proteins/immunology
    • Granulocytes/drug effects
    • Humans
    • Infliximab
    • Leukocyte Count
    • Leukocytes/drug effects
    • Lipopolysaccharide Receptors/immunology
    • Male
    • Methotrexate/administration & dosage
    • Methylprednisolone/therapeutic use
    • Middle Aged
    • Monocytes/drug effects
    • Receptors, IgG/immunology
    • Tumor Necrosis Factor-alpha/therapeutic use

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