Immunophenotyping of peripheral blood monocytes could help identify a baseline pro-inflammatory profile in women with recurrent reproductive failure

• Published in: Journal of reproductive immunology 2022-12, Vol.154, p.103735-103735, Article 103735
• Main Authors: Comins-Boo, Alejandra, Valdeolivas, Lorena, Pérez-Pla, Fernando, Cristóbal, Ignacio, Subhi-Issa, Nabil, Domínguez-Soto, Ángeles, Pilar-Suárez, Lydia, Gasca-Escorial, Pilar, Calvo-Urrutia, Marta, Fernández-Arquero, Miguel, Herráiz, Miguel Ángel, Corbí, Ángel, Sánchez-Ramón, Silvia
• Format: Article
• Language: English
• Subjects: Abortion, Habitual; CCR5; CX3CR1; Cytokines; Female; Flow Cytometry; Humans; Immunophenotyping; Monocytes; Pregnancy; Recurrent Implantation Failure; Recurrent Pregnancy Loss
• ISSN: 0165-0378; 1872-7603
• DOI: 10.1016/j.jri.2022.103735

Recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF) are two well-defined clinical entities, but the role of the monocytes in their pathophysiology needs to be clarified. This study aimed to evaluate the role of the three monocyte subsets (classical, intermediate, and non-classical) and relevant cytokines/chemokines in a cohort of RPL and RIF women to better characterize a baseline proinflammatory profile that could define inflammatory pathophysiology in these two different conditions. We evaluated 108 non-pregnant women: 53 RPL, 24 RIF, and 31 fertile healthy controls (HC). Multiparametric flow cytometry was used to quantify the frequency of surface chemokine receptors (CCR2, CCR5, and CX3CR1) on the monocyte subsets. Cytokines were assessed in plasma samples using a multiplex assay. The CX3CR1+ and CCR5+ intermediate monocytes were significantly higher in RPL and RIF compared to HC. A significant positive correlation was observed between CX3CR1+ intermediate monocytes and IL-17A (P = .03, r = 0.43). The Boruta algorithm followed by a multivariate logistic regression model was used to select the most relevant variables that could help define RPL and RIF: in RPL were CX3CR1 non-classical monocytes, TGF-β1, and CCR5 intermediate monocytes; in RIF: CCR5 intermediate monocytes and TGF-β3. The combination of these variables could predict RPL and RIF with 90 % and 82 %, respectively. Our study suggests that a combination of specific blood monocyte subsets and cytokines could aid in identifying RPL and RIF women with a pro-inflammatory profile. These findings could provide a more integrated understanding of these pathologies. Further investigation and validation in independent cohorts are warranted. •Monocytes/macrophages play a critical role in pregnancy success.•CX3CR1+ and CCR5+ intermediate monocytes were significantly higher in RPL than in healthy mothers.•High intermediate monocytes may reflect a baseline pro-inflammatory state in a subgroup of patients.•We present a Boruta algorithm as a valuable tool to identify women with inflammatory RPL.