Beyond Uterine Natural Killer Cell Numbers in Unexplained Recurrent Pregnancy Loss: Combined Analysis of CD45, CD56, CD16, CD57, and CD138

Abstract

Changes in the number and cytotoxic potential of uterine Natural Killer (uNK) cells have been associated with reduced fertility. To provide a better characterization of immunophenotypes in the endometrium of women with uRPL (unexplained recurrent pregnancy loss), we examined the applicability of a set of five immune cell markers. The concentration (cells/mm²) of CD45⁺ leukocytes, CD56⁺ uNK cells, and CD138⁺ plasma cells as well as of CD16⁺ and CD57⁺ cells, which indicate high cytotoxic uNK cells, were assessed by immunohistochemistry in endometrial biopsies from 61 uRPL patients and 10 controls. Control fertile endometria presented 90–300 CD56⁺ uNK cells/mm². uRPL cases were classified in subgroups of low (uRPL-CD56^low < 90 cells/mm²), normal (uRPL-CD56^normal 90–300 cells/mm²), and high uNK cell counts (uRPL-CD56^high > 300 cells/mm²). Some cases from the uRPL-CD56^low and uRPL-CD56^normal subgroups showed elevated proportions of cytotoxic CD16⁺ and CD57⁺ cells in relation to CD56⁺ cells. In the uRPL-CD56^high subgroup, the CD57/CD56 ratio was reduced in most samples and the CD16/CD56 ratio was unaltered. Analysis of CD138 excluded the influence of chronic endometritis on these observations. Our results reinforce a link between uRPL and a dysfunctional endometrial environment associated with distinct immune cell profiles.