Kwak J Y, Kwak F M, Ainbinder S W, Ruiz A M, Beer A E
Department of Microbiology and Immunology, Finch University of Health Sciences, Chicago Medical School, IL 60060, USA.
Am J Reprod Immunol. 1996 Apr;35(4):363-9. doi: 10.1111/j.1600-0897.1996.tb00495.x.
We investigated the hypothesis that elevated peripheral blood natural killer cells (NK) are decreased by immunoglobulin G infusion (IVIg) therapy in women with recurrent spontaneous abortions (RSA) and elevated NK cells.
Seventy-three women with RSA and elevated NK cells received IVIg therapy (400 mg/Kg/day for 3 days ever 4 wks) and anticoagulation treatment. Peripheral blood immunophenotype assay by flow cytometry was done prospectively prior to and 7 days after first IVIg therapy, every 2 wks until 20 wks gestation and then monthly. Controls were 95 women with RSA and normal NK cells who received anticoagulation treatment.
(1) 86.3% of women with elevated NK cells who received the IVIg and anticoagulation therapy had a successful pregnancy outcome; (2) Peripheral blood CD56+ NK cells and CD56+/16+ NK cells were significantly suppressed 7 days post IVIg infusion (P < 0.0005); (3) Pre-IVIg infusion levels of other lymphocyte subsets were not different as compared with those of 7 days post-IVIg therapy; (4) Women who delivered a liveborn infant with IVIg therapy demonstrated downregulation of peripheral blood NK cells (CD56+, CD56+/16+) during early pregnancy when compared to women who miscarried the index pregnancy (P < 0.05); (5) Women with normal NK cells who miscarried while on anticoagulation therapy demonstrated significantly elevated CD56+ NK cells during early pregnancy as compared with that of women who delivered a liveborn infant (P < 0.05); (6) CD19+ B cells were significantly downregulated during pregnancy in women with anticoagulation and IVIg therapy when compared to women with anticoagulation therapy (P < 0.05).
Downregulation of NK cells in women with RSA is associated with a favorable pregnancy outcome. Peripheral blood NK cells (CD56+, CD56+/16+) are effectively suppressed after IVIg therapy. Women with RSA and high NK cells benefit from IVIg therapy and experience suppression of CD56+ and CD56+/16+ NK cells.
我们研究了这样一个假设，即对于复发性自然流产（RSA）且外周血自然杀伤细胞（NK）升高的女性，静脉输注免疫球蛋白G（IVIg）治疗会使升高的NK细胞数量减少。
73例RSA且NK细胞升高的女性接受了IVIg治疗（400mg/Kg/天，每4周3天）及抗凝治疗。在首次IVIg治疗前及治疗后7天进行前瞻性外周血免疫表型流式细胞术检测，每2周检测一次直至妊娠20周，之后每月检测一次。对照组为95例RSA且NK细胞正常并接受抗凝治疗的女性。
（1）接受IVIg及抗凝治疗且NK细胞升高的女性中，86.3%获得了成功妊娠结局；（2）IVIg输注7天后，外周血CD56⁺NK细胞及CD56⁺/16⁺NK细胞被显著抑制（P<0.0005）；（3）IVIg输注前其他淋巴细胞亚群水平与IVIg治疗7天后相比无差异；（4）与本次妊娠流产的女性相比，接受IVIg治疗并分娩活产婴儿的女性在妊娠早期外周血NK细胞（CD56⁺, CD56⁺/16⁺）表现为下调（P<0.05）；（5）与分娩活产婴儿的女性相比，接受抗凝治疗但流产的NK细胞正常女性在妊娠早期CD56⁺NK细胞显著升高（P<0.05）；（6）与接受抗凝治疗的女性相比，接受抗凝及IVIg治疗的女性在妊娠期间CD19⁺B细胞显著下调（P<0.05）。
RSA女性NK细胞下调与良好的妊娠结局相关。IVIg治疗后外周血NK细胞（CD56⁺, CD56⁺/16⁺）被有效抑制。RSA且NK细胞高的女性从IVIg治疗中获益，且CD56⁺及CD56⁺/16⁺NK细胞受到抑制。
