Dyslipidemia is associated with increased NK cell cytotoxicity and autoimmunity in women with recurrent pregnancy losses

Abstract Context Dyslipidemia adversely affects female fertility; however, its relation with recurrent pregnancy losses (RPL) and underlying mechanism remains unclear. Objective This study aims to analyze the impact of dyslipidemia on natural killer (NK) cell cytotoxicities and autoimmunity in women with RPL and to elucidate how lipids affect cellular immunity. Design A retrospective cross-sectional study with ex vivo experiments. Setting University Clinic. Patients 115 RPL women, including 70 non-dyslipidemia, and 45 dyslipidemia. Interventions Dyslipidemia. Main Outcome Measures Cellular immune activity, and autoimmune parameters were evaluated. Results Out of 115 women, 45 (39.1%) had dyslipidemia. The prevalence of anti-single strand (ssDNA) and anti-thyroglobulin antibodies was significantly higher in dyslipidemia women. Natural killer (NK) cell cytotoxicity, measured at effector to target cell (E: T) ratio of 25:1 and 12.5:1, was significantly higher in women with dyslipidemia (P < 0.05). NK cell cytotoxicities (E:T ratios of 25:1 and 12.5:1) were positively correlated with serum total cholesterol and LDL-C levels (all P < 0.05). However, there were no differences in the T helper 1 (Th1)/Th2 cytokine-producing cell ratios between the two groups. The in-vitro study revealed that pretreatment with oxLDL enhanced the conjugation of NK cells with target cells and increased perforin secretion. NK cell cytotoxicities were significantly increased after pretreatment with 5 and 50 μg/mL oxLDL (P < 0.05 each). Conclusion A significant proportion of women with RPL have dyslipidemia, and the risk of autoimmune and cellular immune abnormalities is increased in women with a history of RPL and dyslipidemia.