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Korean Journal of Reproductive Medicine 2010;37(2):115-124.
Published online June 1, 2010.
Increased Peripheral NK Cell Fraction and Their Cytolytic activity in Patients with History of Recurrent Spontaneous Abortion.
Ji Young Choi, Su Jin Hwang, Ae Ra Han, Ji Hee Yoo, Dong Wook Park, Chan Woo Park, Hye Ok Kim, Sun Hwa Cha, Jin Young Kim, In Ok Song, Mi Kyoung Koong, In Soo Kang, Kwang Moon Yang
1Laboratory of Molecular Oncology, Division of Reproductive Endocrinology & Infertility, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
2Department of Obstetrics & Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
3Laboratory of Reproductive Biology and Infertility, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.
Abstract
OBJECTIVE
To testify whether the increased peripheral blood natural killer (pbNK) cells fraction and their cytolytic activity could coincide with patient's history of recurrent spontaneous abortion (RSA) and to evaluate these factors are can be valuable diagnostic markers in RSA. METHODS: Women with a history of RSA comprised the patient group (n=35). Normal fertile women, who were experienced at least one healthy term birth without history of infertility or recurrent miscarriage, were included as the healthy control group (n=15). The pbNK cells of CD3-/CD56+/CD16+ and their cytolytic activities against K562 cells were measured by flow cytometry and the values were compared between study and control groups. RESULTS: Proportions of pbNK cells among peripheral blood monocytes (PBMC) (14.2+/-5.2 vs. 9.4+/-3.7%, p=0.002, 95% confidence interval [CI], 1.8 to 7.8) was significantly higher in the patient group. The odds ratio of having RSA history was increased as 8.4 folds (59% of sensitivity, 80% of specificity, and 95% CI: 2.0 to 35.8) in patients who showed pbNK cells fraction above 12.1% which was determined as cut-off value by using ROC curve analysis. The cytolytic activities of pbNK cells which measured by three different ratio of effecter pbNK cells to target K562 cells and calculated by the percent of cytolytic K562 cells, were significantly higher in study group than that of control group (in 50:1 ratio, 48.3+/-19.0 vs. 31.3+/-11.9%, p=0.002; in 25:1 ratio, 37.0+/-18.1 vs. 20.2+/-9.2%, p<0.001; in 12.5:1 ratio, 23.5+/-12.7 vs. 12.4+/-7.3%, p=0.001). With the cut-off values of cytolytic activity of pbNK cells as 43.1% (50:1), 26.9% (25:1), and 17.4% (12.5:1) each, the risk of having RSA history was increased by 10.0, 11.4, and 15.0 folds in patients who had increased in each effector of pbNK to target of K562 cells ratio. CONCLUSION: The analysis of pbNK cells fraction and their cytolytic activity can be valuable diagnostic markers for RSA. We are going to planning the large scaled studies which include the data of obstetric outcomes in subsequent pregnancies to clarify our results of this study.
Key Words: CD3-/CD56+/CD16+ peripheral blood natural killer cell; Flow cytometry; Cytolytic activity; Recurrent spontaneous abortion; Digonasitc markers


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