Background/Purpose

Different frequency of monocytes subsets has been reported in rheumatoid arthritis (RA).Human monocytes are divided into three main subpopulations according to expression of the surface markers CD14 and CD16:’classic’ CD14brightCD16- monocytes, ‘non-classic’ CD14dimCD16bright cells and ‘intermediate’ CD14brightCD16bright subpopulation.

Aim: to functionally characterize the different monocytes subsets in RA patients and analyze their role in the endothelial dysfunction, altered oxidative status and proinflammatory/prothrombotic profile associated to RA.

Methods

Thirty RA patients and 15 healthy donors were included in the study. Endothelial function was measured through post occlusive hyperaemia (PORH) using the Laser-Doppler linear Periflux 5010. Classic, intermediate and non-classic monocytes were characterized by flow cytometry. Different proinflammatory cytokines and peroxides levels were analyzed by flow cytometry in the three different subsets.CD14brightCD16- and CD16+ cells were isolated using immuno-magnetic selection.mRNA expression of inflammatory cytokines,endothelial adhesion markers and oxidative enzymes were analyzed in the two monocytes subsets.Correlation studies between clinical parameters, endothelial function and markers of inflammation and endothelial adhesion expressed by the different monocytes subsets were performed.

Results

CD16+(intermediate and non-classic)monocytes were extended in RA patients.These subsets had increased protein expression of TF, IKK and TNFa and lower peroxide levels compared to CD14brightCD16-.CD16+ monocytes displayed higher mRNA expression of TF, TNFa, TLR4, PPARg and MCP-1.In contrast, CD14brightCD16- cells had increased expression of IL8 and oxidative enzymes. All these parameters were significantly increased in RA patients. RA patients had impaired endothelial function, with a reduced perfusion value after ischemia.

Clinical parameters such as evolution time, CRP, anti-CCPs antibodies and rheumatoid factor levels strongly correlated with endothelial dysfunction,decreased percentage of classic monocytes and increased number of non-classic and intermediate subsets.Furthermore, higher expression of proinflammatory/prothrombotic molecules and endothelial adhesion markers in these CD16+ cells correlated with the alteration in endothelial function and the clinical parameters.

Conclusion

RA patients display an increased number of intermediate and non-classic monocytes directly associated to the autoimmune and inflammatory profile, the progression of the disease and the altered microvascular function. Therefore, CD16+ subpopulation might play a key role in the atherothrombotic pathogenesis of RA

Funded by CTS7940, PI12/01511, PI2013-0191, SER

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-monocytes-subsets-in-the-pathology-of-rheumatoid-arthritis-involvement-in-endothelial-dysfunction-and-proinflammatory-profile/