Dyslipidemia Is Associated With Increased Natural Killer Cell Cytotoxicity and Autoimmunity in Women With Recurrent Pregnancy Losses.

Abstract

Context: Dyslipidemia adversely affects female fertility; however, its relation with recurrent pregnancy loss (RPL) and its underlying mechanisms 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: One hundred fifteen RPL women, including 70 nondyslipidemia and 45 dyslipidemia women.

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-stranded and anti-thyroglobulin antibodies was significantly higher in dyslipidemia women. NK cell cytotoxicity, measured at effector to target cell ratio (E:T) of 25:1 and 12.5:1, was significantly higher in women with dyslipidemia (P < .05). NK cell cytotoxicities (E:Ts of 25:1 and 12.5:1) were positively correlated with serum total cholesterol and low-density lipoprotein cholesterol levels (all P < .05). However, there were no differences in the T helper 1 (Th1)/Th2 cytokine-producing cell ratios between the two groups. The ex vivo study revealed that pretreatment with oxidized low density lipoprotein (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 < .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.