Background Evidence suggests that monocyte precursor cells in rheumatoid arthritis (RA) might become partially activated in the bone marrow or the peripheral blood before they enter the rheumatoid synovium. However, whether this is the result of pro-inflammatory cytokines leaking from the inflamed synovium into the circulation or rather a functional abnormality of myeloid cells has not yet been conclusively delineated.
Objectives To test the hypothesis that monocytes in RA might express an intrinsic abnormality for activation, we investigated the function and the phenotype of peripheral blood monocytes from patients with RA and healthy controls in vitro.
Methods Monocytes were isolated by negative selection from patients with active, early RA and from patients with long standing RA under effective anti-inflammatory therapy with disease modifying antirheumatic drugs (DMARDs). A cell culture system was employed that permitted the differentiation of monocytes to macrophages. Expression of surface molecules indicative of activation and/or differentiation was assessed by flow cytometry.
Results No differences were detected for the expression of HLA-DR, CD14, CD40, CD68, CD80 and CD86 on freshly isolated monocytes between patients and controls. During differentiation to macrophages, the expression of HLA-DR, CD14 and CD80 was increased in RA monocytes. Interestingly, patients with untreated, active early disease manifested an even higher propensity to upregulate HLA-DR during differentiation compared to patients with long standing disease under effective anti-inflammatory therapy. In contrast, the expression of CD40, CD68 and CD86 was reduced in myeloid cells from RA patients during differentiation. This feature was more pronounced in patients with long standing disease, but was not correlated with clinical activity.
Conclusion The data indicate that monocytes from RA patients might have an intrinsically increased ability for activation during differentiation. This ability might contribute to clinical disease activity and emphasises the systemic nature of the disease. The data further suggest that long standing disease might alter the functional phenotype of circulating monocytes. However, the contribution of continuous treatment with DMARDs to this phenomenon remains to be elucidated.
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