CD34(+) CD133(+) CD309(+) circulating angiogenic cell level is reduced but positively related to hydroxychloroquine use in SLE patients-a case control study and meta-regression analysis

Objectives. To identify and quantify the level of CD34(+) CD133(+) CD309(+) circulating angiogenic cells (CAC) and explore factors associated with the level of CAC in patients with SLE. Methods. The peripheral blood mononuclear cells of consecutive SLE patients and demographically matched healthy controls (HC) were extracted and identified, enumerated and compared for CAC levels by multi-colour flow cytometry based on the EULAR Scleroderma Trials and Research (EUSTAR) recommendation. Meta-analyses were performed by combining the current and previous case-control studies, aiming to increase the statistical power to discern the difference in CAC level between SLE patients and HC. Mixed-model meta-regression was conducted to explore potential demographic and clinical factors that were associated with CAC level. Results. A lower level of CAC was found in 29 SLE patients compared with 24 HC [mean (S.D.) 10.76 (13.9) vs 24.58 (25.4) cells/ml, P = 0 .015]. Random-effects meta-analyses of the current and six previously published case-control studies involving 401 SLE patients and 228 HC revealed a lower CAC level compared with HC (standardized mean difference=-2.439, P = 0 .001) . Meta-regression analysis demonstrated that HCQ use was associated with a more discrepant CAC level between both groups (P = 0 .01115). Conclusion. SLE patients had a significantly lower CD34(+) CD133(+) CD309(+) CAC level than HC, and HCQ use was associated with a more discrepant CAC level between SLE patients and HC. This study triggers further observational, interventional and mechanistic studies to address the beneficial impact of HCQ on the functionality of CAC in SLE patients.