Journal List > Korean J Obstet Gynecol > v.55(10) > 1088525

TOOLS
Kim, Kim, Jeong, Cha, Choi, and Yang: Changes of natural killer cell number and cytolytic activity during first trimester of pregnancy in recurrent spontaneous abortion patients and fertile control
Original Article
Korean Journal of Obstetrics & Gynecology

Korean Journal of Obstetrics & Gynecology 2012; 55(10): 713-720.

Published online: 10 October 2012

DOI: https://doi.org/10.5468/KJOG.2012.55.10.713

Changes of natural killer cell number and cytolytic activity during first trimester of pregnancy in recurrent spontaneous abortion patients and fertile control

Yun-Hee Kim, MD, Young-Joo Kim, MD, Shin-Ok Jeong, MD, Sun-Hwa Cha, MD, Min-Hye Choi, MD, Kwang Moon Yang, MD, PhD

Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, Seoul, Korea.

Corresponding author: Kwang Moon Yang, MD, PhD. Department of Obstetrics and Gynecology, Cheil General Hospital and Women's Healthcare Center, Kwandong University College of Medicine, 17 Seoae-ro 1-gil, Jung-gu, Seoul 100-380, Korea. Tel: +82-2-2000-7545, Fax: +82-2-2000-7790, km1yang@naver.com

Received 18 June 2012       Revised 1 August 2012       Accepted 24 August 2012

Copyright © 2012. Korean Society of Obstetrics and Gynecology

(open-access):

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

We aimed to evaluate whether natural killer cell (NK cell) numbers and their cytolytic activity are changed in 1st trimester of pregnancy in patients who had history of recurrent spontaneous abortion (RSA).

Methods

Non-pregnant women who had history of RSA (n=48) and 10 patients who had success to get pregnancy comprised the study group. Non-pregnant fertile (n=17) and early pregnant women (n=7) who had history of at least one term birth without history of RSA or infertility were included as controls. %NK cells among peripheral blood lymphocyte and their cytolytic activities are measured.

Results

%NK cells among peripheral blood lymphocyte in RSA patients before pregnancy was significantly higher than that of non-pregnant normal control. NK cell cytolytic activity in non-pregnant RSA patients was significantly higher than that of non-pregnant fertile group. After success to get pregnancy, NK cell cytolytic activity in RSA patients were decreased but were not significantly different compared to that of NK cell cytolytic activity checked at non-pregnant status. NK cell cytolytic activity in pregnant RSA patients was significantly higher than that of pregnant normal control.

Conclusion

Failure to decrease NK cell cytolytic activity in early pregnancy would have pivotal role in failure to sustain pregnancy in RSA patients. Further studies would be needed for clarifying our results.

Keywords: Recurrent spontaneous abortion, Peripheral blood natural killer cell, Natural killer cell cytolytic activity

Figures and Tables

Fig. 1
Determination of immune cell profiles in peripheral blood. Gating strategy for three color flow cytometry evaluation of peripheral blood immune cell. This step descript of analysis gate around lymphocyte (R1), excluding cell debris (A). Next step shows four regions as NK cell, CD3-/16+/56+ (B), NKT cell, CD3+/16+/56+, T cell, CD3+/56- and B cell (CD3-/56-) each. SCC, squamous cell carcinoma; NK cell, natural killer cell.
kjog-55-713-g001
Fig. 2
Determination of peripheral blood natural killer cell (NK cell) cytolytic activities. Figures describes analysis gate around K562 (target cell) live & dead cell in control (A, no effector cell), 50:1 E:T ratio (B), 25:1 E:T ratio (C), and 12.5:1 E:T ratio (D) each which excluding cell debris. E:T, effector cell:target cell; PI, propidum iodie dye.
kjog-55-713-g002
Fig. 3
Comparisons of natural killer cell (NK cell) levels (%) between recurrent spontaneous abortion (RSA) and normal control. aP-value<0.05.
kjog-55-713-g003
Fig. 4
Comparision of natural killer cell (NK cell) cytolytic activity between recurrent spontaneous abortion (RSA) and fertile group. E:T ratio is (A) 50:1, (B) 25:1, (C) 12.5:1. aP-value<0.05.
kjog-55-713-g004
Table 1
Characteristics of patients with RSA group and non-pregnant fertile women and normal early pregnant women
kjog-55-713-i001

Values are presented as mean±standard deviation.

RSA, recurrent spontaneous abortion; NS, not significant; SAB, spontaneous abortion.

References

1. Hannes M, Englert Y, Gotlieb W, Dupont E. Recurrent spontaneous miscarriage. Rev Med Brux. 1992. 13:103–106.
2. Stray-Pedersen B, Stray-Pedersen S. Etiologic factors and subsequent reproductive performance in 195 couples with a prior history of habitual abortion. Am J Obstet Gynecol. 1984. 148:140–146.
3. Mosmann TR, Sad S. The expanding universe of T-cell subsets: Th1, Th2 and more. Immunol Today. 1996. 17:138–146.
4. Marzi M, Vigano A, Trabattoni D, Villa ML, Salvaggio A, Clerici E, et al. Characterization of type 1 and type 2 cytokine production profile in physiologic and pathologic human pregnancy. Clin Exp Immunol. 1996. 106:127–133.
5. Perricone R, De Carolis C, Kroegler B, Greco E, Giacomelli R, Cipriani P, et al. Intravenous immunoglobulin therapy in pregnant patients affected with systemic lupus erythematosus and recurrent spontaneous abortion. Rheumatology (Oxford). 2008. 47:646–651.
6. Kwak JY, Beaman KD, Gilman-Sachs A, Ruiz JE, Schewitz D, Beer AE. Up-regulated expression of CD56+, CD56+/CD16+, and CD19+ cells in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. Am J Reprod Immunol. 1995. 34:93–99.
7. Hussain MJ, Alviggi L, Millward BA, Leslie RD, Pyke DA, Vergani D. Evidence that the reduced number of natural killer cells in type 1 (insulin-dependent) diabetes may be genetically determined. Diabetologia. 1987. 30:907–911.
8. Higuchi K, Aoki K, Kimbara T, Hosoi N, Yamamoto T, Okada H. Suppression of natural killer cell activity by monocytes following immunotherapy for recurrent spontaneous aborters. Am J Reprod Immunol. 1995. 33:221–227.
9. King K, Smith S, Chapman M, Sacks G. Detailed analysis of peripheral blood natural killer (NK) cells in women with recurrent miscarriage. Hum Reprod. 2010. 25:52–58.
10. Aoki K, Kajiura S, Matsumoto Y, Ogasawara M, Okada S, Yagami Y, et al. Preconceptional natural-killer-cell activity as a predictor of miscarriage. Lancet. 1995. 345:1340–1342.
11. Rezaei A, Dabbagh A. T-helper (1) cytokines increase during early pregnancy in women with a history of recurrent spontaneous abortion. Med Sci Monit. 2002. 8:CR607–CR610.
12. Vassiliadou N, Bulmer JN. Functional studies of human decidua in spontaneous early pregnancy loss: effect of soluble factors and purified CD56+ lymphocytes on killing of natural killer- and lymphokine-activated killer-sensitive targets. Biol Reprod. 1998. 58:982–987.
13. Cooper MA, Fehniger TA, Caligiuri MA. The biology of human natural killer-cell subsets. Trends Immunol. 2001. 22:633–640.
14. Lanier LL, Le AM, Ding A, Evans EL, Krensky AM, Clayberger C, et al. Expression of Leu-19 (NKH-1) antigen on IL 2-dependent cytotoxic and non-cytotoxic T cell lines. J Immunol. 1987. 138:2019–2023.
15. Lachapelle MH, Miron P, Hemmings R, Roy DC. Endometrial T, B, and NK cells in patients with recurrent spontaneous abortion. Altered profile and pregnancy outcome. J Immunol. 1996. 156:4027–4034.
16. Emmer PM, Veerhoek M, Nelen WL, Steegers EA, Joosten I. Natural killer cell reactivity and HLA-G in recurrent spontaneous abortion. Transplant Proc. 1999. 31:1838–1840.
TOOLS
Similar articles