Background/Purpose: Structural changes, increased tissue citrullination and signs of local inflammation are present in the pulmonary compartment of early seropositive RA and seropositive individuals at risk for developing RA. Cell-derived Microvesicles (MVs) are small particles (0.1-1.0 microns), formed by the outward blebbing of the plasma cell membrane, that can be released during and further contribute to inflammation. The MVs express surface markers similar to the cell of origin and have previously shown to induce tissue injury in the lung. We aimed to study the role of MVs in the lungs of early RA.

Methods: Bronchoalveolar lavage (BAL) fluid was obtained from 20 RA patients (8 females, 12 males, 16 sero-positive and 4 sero-negative, 9 smokers and 11 non-smoker, 59 median age). Additionally BAL samples from disease controls (10 patients with sarcoidosis with active lung inflammation) and healthy volunteers (n=3) were collected. Microvesicles derived from macrophage, endothelial cells, lymphocytes and T-cells were analysed by flow cytometry for phosphatidylserine, CD45, CD63E, CD68, CD154 and CD163 expression. Anti citrullinated protein antibodies (ACPA) were purified from the peripheral blood of RA patients by affinity chromatography, fluorescent labeled and used to identify expression of citrullinated proteins in MVs using flow cytometry.

Results: Elevated numbers of total MVs were observed in the BAL of RA (Mean±SD, 526.2±291.7, events/μL) compared with disease controls (402.3±107.5, p>0.05) and healthy volunteers (283.0±52.8, p<0.05). MVs derived from macrophage, endothelial cell and lymphocytes were significant increased in the BAL of RA patients (27.2± 13.4, events/μL for macrophage derived MVs, 20.8±9.0 for endothelial derived MVs and 47.7±24.4 for lymphocytes derived MVs) as compared to both disease controls (16.1±6.0 for macrophage derived MVs, 12.3±3.6 for endothelial derived MVs and 25.1±11.9 for lymphocytes derived MVs) and healthy volunteers (5.9±1.9 for macrophage derived MVs, 10.1±2.9 for endothelial derived MVs and 8.1±5.0 for lymphocytes derived MVs), (p<0.05 for all comparisons). Citrulline containing MVs, detected by ACPA were significantly higher in RA compared to disease controls (6.6±2.7 vs 4.3±1.1, p<0.05) and healthy BAL (6.6±2.7 vs 3.3±1.4, p<0.05) whereas no such difference and significantly lower amount of MVs were detected using RA-derived IgGs others than ACPA as controls.

Conclusion: MVs and citrulline-containing MVs are present in the RA BAL in a higher proportion than in the BAL of either patient with inflammatory lung disease (sarcoidosis) and healthy controls, suggesting a role for MVs in RA-associated lung changes. Confirmation of current findings in larger samples and investigation of potential pathogenic effects of MVs are needed.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/microvesicles-in-the-lungs-of-early-rheumatoid-arthritis/