Antibodies to phosphatidylethanolamine and phosphatidylserine are associated with increased natural killer cell activity in non-male factor infertility patients

Abstract

Antiphospholipid antibodies (APA) have been identified in patients with recurrent pregnancy loss and IVF failure. Of these, antiphosphatidylethanolamine (aPE) and antiphosphatidylserine (aPS) may have special significance. A link between increased natural killer cell activity (NKa+) and trophoblast cell apoptosis has also been reported. This study was undertaken to determine how the APA profile was associated with peripheral NK cell activity. We evaluated 197 female IVF candidates for APA and NKa. Eighty-nine patients (45%) were APA+ and of these, 51 (57%) were aPE/aPS+. Fifty-four patients (27%) had increased NK cell activity. Some 51% of APA+ and 78% of aPE/aPS+ patients had increased NK cell activity compared with 8% and 13% when APA and aPE/aPS tested negative respectively (P: < 0.0001). Non-male factor infertility patients were APA+ and NKa+ in 57% and 34% of cases respectively, compared with 19% and 13% if a pure male factor was present. Some 88% of aPE/aPS+, non-male factor patients had increased NK cell activity, compared with 12% who tested aPE/aPS negative (P: < 0.0001) and 25% of aPE/aPS+, isolated male factor patients (P: < 0.0001). These findings establish a direct relationship between APA (specifically aPE/aPS) and increased peripheral NK cell activity among non-male factor infertility patients. It is possible that APA do not directly cause reproductive failure but rather function as markers or intermediaries for an underlying, abnormal activation of cellular immunity.

Management of Obstetric Antiphospholipid Syndrome

“…They may affect implantation, placentation, and early embryonic development, as the antibody binds to b2 GP I and is responsible for breakdown of the phospholipids' adhesion molecules between different elements of trophoblast [10]. A 2000 meta-analysis concluded that there was no significant association between the presence of aPLs and either the clinical pregnancy rate or live birth rate in in vitro fertilization patients [11], but in this study, other antibodies besides aCL and LA, such as antiphosphatidylserine and antiphosphatidylethanolamine, had a positive relationship with increased natural killer cell activity among infertile women with non-male factor undergoing in vitro fertilization [12], and there is an elevated prevalence of these new antibodies among in vitro fertilization failure patients [13]. Further studies should be conducted to help us better understand the association between aPLs and infertility.…”

NK Cells, Autoantibodies, and Immunologic Infertility: A Complex Interplay

“…It has been demonstrated that APE and APS positivity in female infertility was associated with increased NK cell activity and decreased IVF success, which did not happen if the APE/APS were found in isolated male factor infertility. Thus, again in this study, APL were considered not as causally related to reproductive failure, rather as markers or intermediaries of an underlying abnormal cellular immunity [73].…”

The Means of Progress in Improving the Results of in vitro Fertilization Based on the Identification and Correction of the Pathology of Hemostasis

“…Women with APS demonstrate high level of NK cells in the peripheral blood and endometrium. It is possible that disturbed synthesis of mediator molecules which participate in embryo adhesion and invasion by NK cells is one of the causes of disturbed signaling interaction between the blastocyst and endometrium on the earliest implantation stages (Quenby et al, 2009;Sher et al, 2000). APLAs stimulate PAI-1 synthesis that may cause disturbed degradation of intercellular matrix and decreased depth of blastocyst invasion.…”