Endometrial immune markers are upregulated in the proliferative and secretory phases in recurrent pregnancy loss

Immune factors in the endometrium of women with recurrent pregnancy loss (RPL) appear to play a crucial role in the pathophysiology of a subset of RPL patients. Differences in the expression of five immune markers, CD138 (plasma cells), CD56 (uterine natural killer (uNK) cells), CD163 (M2 macrophages), soluble HLA-G and HLA-F, were studied in the preconceptional endometrium between women with RPL and control/reference women, and also between the proliferative and secretory phases. The RPL group included 96 patients. One reference group (n = 58) comprised women referred for IVF/ICSI treatment; another control group (n = 22) consisted of healthy fertile women. Endometrial biopsies were subjected to immunohistochemistry analysis; 118 biopsies from the proliferative phase, 55 from the secretory phase and three from inactive endometrium. Increased levels of CD56-positive uNK cells and sHLA-G expression in the proliferative phase and of CD138-positive plasma cells in the secretory phase were observed in the RPL group compared with the other groups. High expression of CD56 in uNK cells and high HLA-F-positive cell fraction in the glands in the proliferative phase served as negative predictors for achieving a successful pregnancy for women with RPL in Cox regression analyses. Follow-up for 45 months. A new finding was an intense sHLA-G staining of intracellular vesicles in the glands of some biopsies in the RPL group associated with the achievement of a healthy pregnancy. Increased levels of the preconceptional endometrial markers CD56 (uNK cells), HLA-F, sHLA-G and CD138 (plasma cells) may contribute to the pathophysiology of RPL.