PloS one, 2012, Vol.7 (1), p.e28918
2012
Details
- Autor(en) / Beteiligte
- Titel
- FcγRIIIa expression on monocytes in rheumatoid arthritis: role in immune-complex stimulated TNF production and non-response to methotrexate therapy
- Ist Teil von
- PloS one, 2012, Vol.7 (1), p.e28918
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The expression of FcγRIIIa/CD16 may render monocytes targets for activation by IgG-containing immune complexes (IC). We investigated whether FcγRIIIa/CD16 was upregulated in rheumatoid arthritis (RA), associated with TNF production in response to IC-stimulation, and if this predicted response to methotrexate therapy. FcγRIIIa/CD16 expression on CD14(low) and CD14++ monocytes was measured by flow cytometry in healthy controls and RA patients (early and long-standing disease). Intracellular TNF-staining was carried out after in vitro LPS or heat-aggregated immunoglobulin (HAG) activation. FcγRIIIa/CD16 expression pre- and post-steroid/methotrexate treatment was examined. Increased FcγRIIIa/CD16 expression on CD14++ monocytes in long-standing RA patients compared to controls was demonstrated (p = 0.002) with intermediate levels in early-RA patients. HAG-induced TNF-production in RA patients was correlated with the percentage of CD14++ monocytes expressing FcγRIIIa/CD16 (p<0.001). The percentage of CD14++ monocytes expressing FcγRIIIa/CD16 at baseline in early DMARD-naïve RA patients was negatively correlated with DAS28-ESR improvement 14-weeks post-methotrexate therapy (p = 0.003) and was significantly increased in EULAR non-responders compared to moderate (p = 0.01) or good responders (p = 0.003). FcγRIIIa/CD16 expression was not correlated with age, presence of systemic inflammation or autoantibody titers. Increased FcγRIIIa/CD16 expression on CD14++ monocytes in RA may result in a cell that has increased responsiveness to IC-stimulation. This monocyte subset may contribute to non-response to methotrexate therapy.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0028918Titel-ID: cdi_plos_journals_1322070907
- Format
- –
- Schlagworte
- Adult, Aged, Aged, 80 and over, Antigen presentation, Antigen-antibody complexes, Arthritis, Arthritis, Rheumatoid - drug therapy, Arthritis, Rheumatoid - immunology, Arthritis, Rheumatoid - metabolism, Autoantibodies, Biology, Biomedical research, Case-Control Studies, CD14 antigen, CD16 antigen, Cell activation, Collagen, Consortia, Correlation, Cytokines, Cytometry, Dendritic cells, Disease control, Female, Flow cytometry, Gene Expression Regulation - drug effects, Gene Expression Regulation - immunology, Humans, Immunoglobulin G, Lipopolysaccharide Receptors - metabolism, Lipopolysaccharides, Male, Medicine, Methotrexate, Methotrexate - pharmacology, Methotrexate - therapeutic use, Middle Aged, Minority & ethnic groups, Monocytes, Monocytes - drug effects, Monocytes - immunology, Monocytes - metabolism, Pathogenesis, Patients, Receptors, IgG - metabolism, Retrospective Studies, Rheumatism, Rheumatoid arthritis, Rheumatology, Steroids - therapeutic use, Stimulation, Studies, Therapy, TNF inhibitors, Treatment Outcome, Tumor necrosis factor, Tumor Necrosis Factor-alpha - biosynthesis, Tumor necrosis factor-TNF, Young Adult