Aberrant integrin expression on peripheral blood NK cells of women with recurrent pregnancy losses and repeated implantation failures.

Natural killer (NK) cells are key regulators of endometrial receptivity and placentation, and aberrant activation of peripheral blood NK (pNK) cells has been implicated in recurrent pregnancy loss (RPL) and repeated implantation failure (RIF). This study investigated adhesion molecule expression on pNK cells in women with primary RPL (pRPL), secondary RPL (sRPL), and unexplained infertility (uINF), and its associations with NK-cell phenotypes, cytotoxicity (NKC), and T-helper (Th)-1/Th2 (Th1/Th2) immune balance. Expression of adhesion markers LFA-1, VLA-1, VLA-2, and ICAM-1 on NK cells was assessed by flow cytometry. NKC was measured using the K562 assay, and Th1/Th2 cytokine ratios were determined by intracellular cytokine staining using flow cytometry. Total CD56⁺ NK cell proportions and overall NKC did not differ among groups. Expression of LFA-1, VLA-1, VLA-2, and ICAM-1 on total NK cells was also comparable. However, Th1/Th2 cytokine ratios were significantly lower in the sRPL group. Stratification by NKC revealed that women with RPL and higher NKC exhibited significantly increased ICAM-1 expression on cytotoxic subsets (CD56⁺CD16⁺ and CD56⁺CD57⁺). NKC positively correlated with ICAM-1-expressing NK subsets, while Th1/Th2 ratios were associated with mature and activated NK phenotypes in women with RPL. Although overall adhesion molecule expression did not differ by clinical classification, elevated ICAM-1 expression was associated with increased NKC and pro-inflammatory immune signatures in RPL but not in uINF, suggesting an association between ICAM-1 expression on NK cell subsets, increased NKC, and altered Th1/Th2 responses in RPL.