Endothelial Progenitor Cell CD34 + and CD133 + Concentrations and Soluble HLA-G Concentrations During Pregnancy and in C

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PREGNANCY: ORIGINAL ARTICLE

Endothelial Progenitor Cell CD34+ and CD133+ Concentrations and Soluble HLA-G Concentrations During Pregnancy and in Cord Blood in Undifferentiated Connective Tissue Diseases Compared to Controls Fausta Beneventi 1 & Irene De Maggio 1 & Chiara Cavagnoli 1 & Camilla Bellingeri 1 Greta Riceputi 1 & Gianluca Viarengo 2 & Véronique Ramoni 3 & Arsenio Spinillo 1

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Beatrice Ruspini 1

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Received: 3 July 2020 / Accepted: 16 November 2020 # Society for Reproductive Investigation 2020

Abstract The objective of this study is to evaluate endothelial progenitor cells (EPCs) CD34+ CD133− and CD34+ CD133+ and soluble HLA-G (sHLA-G) concentrations among undifferentiated connective tissue disease (UCTD) subjects, compared to controls, during pregnancy and in cord blood. This is a case-control study including 29 controls and 29 UCTDs. CD34+ CD133−, CD34+ CD133+, and sHLA-G concentrations were detected in maternal plasma and in cord blood. This study was approved by the Medical-Ethical Committee of our Institution (Current Research Project N. 901-rcr2017i-23 of IRCCS Foundation Policlinico San Matteo of Pavia). Circulating CD34+ CD133− and CD34+ CD133+ counts and sHLA-G (soluble human leucocyte antigen G) concentrations in maternal peripherical blood were higher in UCTD compared to those in controls in first and third trimester of pregnancy and at delivery (p < 0.001). Maternal CD34+ CD133− and CD34+ CD133+ counts were strongly and significantly correlated in UCTD (Spearman’s rho = 0.79, p < 0.0001) but not in controls (Spearman’s rho = 0.10, p = 0.35). Cord blood CD34+ CD133− and CD34+ CD133+ median counts and median sHLA-G concentrations were higher among UCTD subjects than in controls (p < 0.001). Cord blood CD34+ and CD133+ counts were inversely and significantly correlated with sHLA-G concentrations among UCTDs, but not in controls. Early UCTD is characterized by increased EPC levels in maternal plasma and in cord blood and higher levels of sHLA-G, compared to controls. Data suggest that fetoplacental unit plays an independent role in the EPC response to a systemic autoimmune disease. Keywords Pregnancy . Circulating endothelial progenitor cells . HLA-G . Undifferentiated connective tissue diseases

Introduction Circulating endothelial progenitor cells (EPCs) play a significant role both in vasculogenesis and in vascular repair in endothelial injury associated with autoinflammation [1].

* Irene De Maggio [email protected] 1

Department of Obstetrics and Gynecology, IRCCS Foundation Policlinico San Matteo, University of Pavia, Viale Golgi 19, 27100 Pavia, Italy

2

Immunohaematology and Transfusion Service, IRCCS Foundation Policlinico San Matteo, 27100 Pavia, Italy

3

Division of Rheumatology, IRCCS Foundation Policlinico San Matteo, University of Pavia, 27100 Pavia, Italy

Early circulating EPCs could be recognized by the coexpression of CD34 and CD133. In the transition from bone marrow towards the blood stream, EPCs would lose CD133; therefore, the co-expression of the stem cell ant