Identification of a unique intervillous cellular signature in chronic histiocytic intervillositis.

Introduction: Chronic histiocytic intervillositis (CHI) is a rare histopathological lesion in the placenta characterized by an infiltrate of CD68 cells in the intervillous space. CHI is associated with adverse pregnancy outcomes such as miscarriage, fetal growth restriction, and (late) intrauterine fetal death. The adverse pregnancy outcomes and a variable recurrence rate of 25-100% underline its clinical relevance. The pathophysiologic mechanism of CHI is unclear, but it appears to be immunologically driven. The aim of this study was to obtain a better understanding of the phenotype of the cellular infiltrate in CHI.

Method: We used imaging mass cytometry to achieve in-depth visualization of the intervillous maternal immune cells and investigated their spatial orientation in situ in relation to the fetal syncytiotrophoblast.

Results: We found three phenotypically distinct CD68HLA-DRCD38 cell clusters that were unique for CHI. Additionally, syncytiotrophoblast cells in the vicinity of these CD68HLA-DRCD38 cells showed decreased expression of the immunosuppressive enzyme CD39.

Discussion: The current results provide novel insight into the phenotype of CD68 cells in CHI. The identification of unique CD68 cell clusters will allow more detailed analysis of their function and could result in novel therapeutic targets for CHI.