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Screening of endometrial NK cells in selected infertile patients
First part – Methods and current results


Authors: Z. Ulčová-Gallová 1,2;  M. Pešek 3;  P. Chaloupka 3;  P. Mukešnábl 4;  M. Haschová 5;  P. Losan 1;  K. Bibková 1;  Z. Mičanová 1;  J. Cibulka 1
Authors place of work: Genetika-Plzeň, s. r. o., přednosta MUDr. P. Lošan 1;  Gynekologicko-porodnická klinika LF UK, Plzeň, přednosta doc. MUDr . Z. Novotný, CSc. 2;  Mulačova nemocnice, gynekologicko-porodnické oddělení, přednosta MUDr. Z. Knaizl 3;  Šiklův patologicko-anatomický ústav LF UK a FN, Plzeň, přednosta prof. MUDr. M. Michal 4;  MN Privamed a. s., OKB, přednosta Ing. Z. Jeřábek 5
Published in the journal: Ceska Gynekol 2017; 82(5): 366-371

Summary

Introduction:
Generaly, natural killer cells (NK cells) are among the most important cells of our immune defense system. They are present in the blood, decidua but also in secretory endometrium.

Objective:
We investigate an association between high density of NK cells CD56+ and NK cells CD16+ into blood and secretory endometrium in patients with up to now unexplained recurrent miscarriage. At the same time, we focused on diagnosis of antiphospholipid syndrome, congenital trombophilic factors, stress factor, and lenght of hormonal contraception before conception.

Design:
Original work-prospective study.

Setting:
Genetics-Pilsen.

Methods:
We investigated 59 patients aged 25–41 (average 34) years with their history of 3–9 abortions. We monitored their blood cells by flow cytometry and endometrium obtained by hysteroscopy performed on the 22nd–24th day of the menstrual cycle. We concentrated on the cellular immunity focused on the identification of lymphocytes CD56+ and CD16+. ELISA method was used for identification of antiphospholipid antibodies.

Results:
Our study goes on, we are publishing our preliminary results.

We found a high density of endometrial NK cells CD56+ in 41/57, NK cells CD16+ in 40/57, both NK cells CD56+ and CD16+ in 36/57 patients. In 13 women, we identified only sporadically these cells in the secretory endometrium. NK cells CD56+ and NK cells CD16+ in the blood were all normal number in all our patients. Three of them have a homozygot form of Leiden mutation, and 18/57 primary antiphospholipid syndrome, 12 women have university education, four of them, medical doctors, have regular night services in the hospital.

Conclusion:
Overproduction of endometrial NK cells is associated with increased local activity of embryocytotoxic cytokines that may negatively affect pregnancy. Treatment of patients with pathological immunological findings must be solved individually, as we will show soon in part two of our study.

Keywords:
infertility, natural killer cells, endometrium


Zdroje

1. De Maria, A., Bozzano, F., Cantoni, C., et al. Revisiting human natural killer cell subset function revealed cytolytic CD56 CD16+ NK cells as rapid producers of abudant IFN-gamma on activation. Proc Natl Acad Sci USA, 2011, 108, p. 728–732.

2. Eshadri, S., Sunkara, SK. Natural killer cells in female infertility and recurrent miscarriage: a systemic review and meta-analysis. Human Reprod Update, 2014, 20, p. 429–438.

3. Hanzlikova, J., Ulcova-Gallova, Z., Malkusova, I., et al. Th1-Th2 response and the atopy risk in patients with reproductive failure. Am J Reprod Immunol, 2009, 61, p. 213–220.

4. Krejsek, J., Kopecký, O. Klinická imunologie. Nucleus, 2004, s. 1–939.

5. Kuon, RJ., Vomstein, K., Weber, M., et al. The „killer cell story“ in recurrent miscarriage: Association between activated peripheral lymphocytes and uterine natural killer cells. J Reprod Immunol, 2017, 119, p. 9–14.

6. Kwak-Kim, J., Bao, S., Lee, SK., et al. Immunological modes of pregnancy loss: inflammation, immune effectors, and stress. Am J Reprod Immunol, 2014, 72, p. 129–140.

7. Lee, SK., Na, BJ., Kim, JY., et al. Determination of clinical cellular immune markers in women with recurrent pregnancy loss. Am J Reprod Immunol, 2013, 70, p. 398–411.

8. Leno-Duran, E., Munoz-Fernandez, R., Olivares, EG., et al. Liaison between natural killer cells and dendritic cells in human gestation. Cell Mol Immunol, 2014, 11, p. 449–455.

9. Manaster, I., Mandelboim, O. The unique properties of uterine NK cells. Am J Reprod Immunol, 2010, 63, p. 434–444.

10. Quenby, S., Farquharson, R. Uterine natural killer cells, implantation failure and recurrent miscarriage. Reprod Biomed Online, 2006, 13, p. 24–28.

11. Seshadri, S., Sunkara, SK. Natural killer cells in female infertility and recurrent miscarriage: a systematic review and metaanalysis. Hum Reprod Update, 2014, 20, p. 429–438.

12. Tang, AW., Alfirevic, Z., Quenby, S. Natural killer cells and pregnancy outcomes in women with recurrent miscarriages and infertility: a systemic review. Hum Reprod, 2011, 26, p. 1971–1980.

13. Thum, MY., Bhaskaran, S., Bansal, AS., et al. Simple enumerations of peripheral blood natural killer (CD56+NK) cells, B cells and T cells have no predictive value in IVF treatment outcome. Hum Reprod, 2005, 20, p. 1272–1276.

14. Ulcova-Gallova, Z., Bibkova, K., Micanova, Z., Losan, P., et al. Possible effect of extended use of hormonal contraception on increased levels of antiphospholipid antibodies in infertile women. Geburtshilfe Frauenheilkd. 2015, 75, p. 251–254.

15. Vassiliadou, N., Searle, RF., Bulmer, JN. Elevated expression of activation molecules by decidual lymphocytes in women suffering spontaneous early pregnancy loss. Hum Reprod, 1999, p. 194–200.

Štítky
Dětská gynekologie Gynekologie a porodnictví Reprodukční medicína

Článek vyšel v časopise

Česká gynekologie

Číslo 5

2017 Číslo 5

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