Spontan abortus ve istemli gebelik tahliyesi olgularında desiduada T lenfosit subgrupları ve uterin doğal öldürücü hücre sayılarının immunohistokimyasal yöntem ile karşılaştırılması

Semir Köse; Serap Karaarslan Takmaz; Murat Ulukuş; Osman Zekioğlu; Hüseyin Yılmaz

doi:10.19161/etd.551214

EN TR

An immunohistochemical staining study for comparison of the T lymphocyte subgroups and the uterine natural killer cells in the decidua from spontaneous abortions and voluntary pregnancy terminations

Abstract

Aim: To investigate the role of the decidual total T lymphocyte count, T cytotoxic (Tc) and T helper (Th) sub-populations and the uterin natural killer (uNK) cells in the pathogenesis of the spontaneous abortions (SA) and recurrent pregnancy loss (RPL) cases.

Materials and Methods: We included the SA (n:29) and the voluntary pregnancy termination (n:10) cases which were undergone suction curettage between January 2003-January 2005 at the Ege University Obstetrics and Gynecology Department and their paraffin blocks were obtained.

Results: Median CD3+ T lymphocyte cell counts were not different between the control (314; 210-489), incomplete abortions (560;183-1602) and missed abortions (426;154-1102) groups (p:0.117). Median CD4+ Th cell counts were not different between the control (143; 87-203), incomplete abortions (236;77-735) and missed abortions (236;76-677) groups (p:0.441). Median CD8+ Ts cell counts were not different between the control (179; 105-279), incomplete abortions (239;90-820) and missed abortions (197;84-560) groups (p:0.530). Median CD56+ uNK cell counts were not different between the control (634; 554-1390), incomplete abortions (714;653-2165) and missed abortions (712;306-2108) groups (p:0.099).

Conclusion: Abortions and RPL are heterogeneous groups consisting of cases representing various pathogenetic origins. Aberrant immune mechanisms could be responsible for a subgroup if not in all cases. Further studies designed by classifying the cases karyotypically and utilizing more sophisticated methods (such as flow cytometry, gene expression and receptor activation analyses) are needed to elucidate the complicated role of the immune system elements in the spontaneous abortion cases.

Keywords

Abortion,decidua,recurrent pregnancy loss,T lymphocytes,uterine natural killer cells.

Spontan abortus ve istemli gebelik tahliyesi olgularında desiduada T lenfosit subgrupları ve uterin doğal öldürücü hücre sayılarının immunohistokimyasal yöntem ile karşılaştırılması

Öz

Amaç: Desiduada T lenfositlerin toplam sayılarının, sitotoksik (Ts) ve helper (Th) alt gruplarının ve uterin naturel killer (uNK) hücre sayılarının abortuslar ve tekrarlayan gebelik kayıplarının (TGK) patogenezindeki rolünün araştırılması hedeflenmiştir.
Gereç ve Yöntem: Ocak 2003- Ocak 2005 tarihleri arasında Ege Üniversitesi Kadın Hastalıkları ve Doğum kliniğinde gebelik tahliyesi yapılmış ve küretaj materyallerine ait parafin blokları elde edilen abortus (n:29) ve sağlıklı kontrol olarak isteğe bağlı gebelik tahliyeleri (n:10) olguları çalışmaya dahil edildi. Tüm T lenfositler için ortak belirteç CD3, Th için CD4, Ts için CD8 ve uNK hücreleri için CD56 belirteçleri ile seçici immunohistokimyasal boyama sağlandı ve her preparat için 10 alanda hücreler sayıldı.

Bulgular: Medyan CD3+ T lenfosit toplam hücre sayıları kontrol grubunda 314 (210-489), inkomplet abortus grubunda 560 (183-1602) ve missed abortus grubunda ise 426 (154-1102) idi (p: 0.117). Medyan CD4+ Th hücre sayıları kontrol grubunda 143 (87-203), inkomplet abortus grubunda 236 (77-735) ve missed abortus grubunda ise 236 (76-677) idi (p: 0.441). Medyan CD8+ Ts hücre sayıları kontrol grubunda 179 (105-279), inkomplet abortus grubunda 239 (90-820) ve missed abortus grubunda 197 (84-560) idi (p:0.530). Medyan CD56+ uNK hücre sayıları kontrol grubunda 634 (554-1390), inkomplet abortus grubunda 714 (653-2165) ve missed abortus grubunda 712 (306-2108) idi (p:0.099).

Sonuç: Abortuslar ve TGK heterojen gruplardır ve farklı patogeneze sahip olgulardan oluşmaktadır. Bir alt grupta immün mekanizmalar nedensel rol oynuyor olabilir. Öncelikle karyotip analizi ile kategorize edilmiş gruplarda daha güncel metodlarla (akış sitometri, gen ekspresyon ve reseptör aktivasyon analizleri) yapılacak ileri çalışmalar abortuslarda immün sistem elemanlarının karmaşık rolünün aydınlatılması için gerekli görünmektedir.

Anahtar Kelimeler

Abortus,desidua,tekrarlayan gebelik kayıpları,T lenfositler,uterin doğal öldürücü hücreler.

References

Medawar PD. Some immunological and endocrinological problems raised by the evolution of viviparity in vertebrates. Symposium of the Society for Experimental Biology 1953: p. 320.
Veenstra van Nieuwenhoven AL, Heineman MJ, Faas MM. The immunology of successful pregnancy. Hum Reprod Update 2003;9(4):347-57.
Piccinni MP, Romagnani S. Regulation of fetal allograft survival by a hormone-controlled Th1- and Th2-type cytokines. Immunol Res 1996;15(2):141-50.
Clark DA, Coulam CB, Daya S, Chaouat G. Unexplained sporadic and recurrent miscarrage in the new millennium: a critical analysis of immune mechanisms and treatments. Hum Reprod Update 2001;7(5):501-11.
Burgoyne PS, Holland K, Stephens R. Incidence of numerical chromosome anomalies in human pregnancy estimation from induced and spontaneous abortion data. Hum Reprod 1991;6(4):555-65.
King A. Uterine leukocytes and decidualization. Hum Reprod Update 2000;6(1):28-36.
Blalock JE, Harbour-McMenamin D, Smith EM. Peptide hormones shared by the neuroendocrine and immunologic systems. J Immunol 1985;135(Supll 2):858-861.
Henderson TA, Saunders PT, Moffett-King A, Groome NP, Critchley HO. Steroid receptor expression in uterine natural killer cells. J Clin Endocrinol Metab 2003;88(1):440-9.

Dosiou C, Giudice LC. Natural killer cells in pregnancy and recurrent pregnancy loss: endocrine and immunologic perspectives. Endocr Rev 2005;26(1):44-62.
Vassiliadou N, Bulmer JN. Quantitative analysis of T lymphocyte subsets in pregnant and nonpregnant human endometrium. Biol Reprod 1996;55(5):1017-1022.
Mincheva-Nilsson L, Baranov V, Yeung MM-Y, et al. Immunomorphologic studies of human decidua associated lymphoid cells in normal early pregnancy. J Immunol 1994;152(4):2020-2032.
Morii T, Nishikawa K, Saito S, et al. T cell receptors are expressed but down-regulated on intradecidual T lymphocytes. Am J Reprod Immunol 1993;29(1):1-4.
Lachapelle MH, Miron P, Hemmings R, And Roy DC. Endometrial T, B and NK cells in patients with recurrent spontaneous abortion. J Immunol 1996;156(10):4027-4034.
Quenby S, Bates M, Doig T, et al. Preimplantation endometrial leukocytes in women ith recurrent miscarriage. Hum Reprod 1999;14(9):2386-2391.
King A, Balendran N, Wooding P, et al. CD3- leukocytes present in the human uterus during early presetantion: phenotypic and morphologic characterization of the CD56+ population. Dev Immunol 1991;1(3):169-190.
Bulmer JN, Johnson PM, and Bulmer D. Leukocyte populations in human decidua and endometrium. In: Gill TJ and Wegmann TG. (eds). Immunoregulation and Fetal Survival. New York: Oxford University Press; 1987:111-134.
Vassiliadou N, Bulmer JN. Immunohistochemical evidence for increased numbers of ‘classic’ CD57+ natural killer cells in the endometrium of women suffering spontaneous early pregnancy loss. Hum Reprod 1996;11(7):1569-1574.
King A, Loke YW. On the nature and function of human uterine granular lymphocytes. Immunol Today 1991;12(12):432-435.
Liu S, Diao L, Huang C, Li Y, Zeng Y, Kwak-Kim JYH. The role of decidual immune cells on human pregnancy. J Reprod Immunol 2017; 124:44-53.
Mori M, Bogdan A, Balassa T, Csabai T, Szekeres-Bartho J. The decidua-the maternal bed embracing the embryo-maintains the pregnancy. Semin Immunopathol 2016;38(6):635-649.
Vassiliadou N, Bulmer JN. Characterization of endometrial T lymphocyte subpopulations in spontaneous early pregnancy loss. Hum Reprod 1998;13(1):44-47.
Chao K-H, Yang Y-S, Ho H-N, et al. Decidual natural killer cytotoxicity decreased in normal pregnancy but not in embryonic pregnancy and recurrent spontaneous abortion. Am J Reprod Immunol 1995;34(5):274-280.
King A, Burrows T, Verma S, et al. Human uterin lymphocytes. Hum Reprod Update 1998;4(5):480-485.
Wegmann TG, Lin H, Guilbert L, Mosmann TR. Bidirectional cytokine interactions in the maternal-fetal relationship: is successful pregnancy a TH2 phenomenon? Immunol Today 1993;14(7):353-356.
Sykes L, MacIntyre DA, Yap XJ, Teoh TG, Bennett PR. The Th1:th2 dichotomy of pregnancy and preterm labour. Mediators Inflamm 2012; 2012: 967629.
Chaouat G, Menu E, Clark DA, Dy M, Minkowski M, Wegmann TG. Control of fetal survival in CBA x DBA/2 mice by lymphokine therapy. J Reprod Fertil 1990;89(2):447-458.
Sabahi F, Rola-Plesczcynski M, O'Connell S, Frenkel LD. Qualitative and quantitative analysis of T lymphocytes during normal human pregnancy. Am J Reprod Immunol 1995;33(5):381-393.
Makhseed M, Raghupathy R, Azizieh F, Al Azemi MM, Hassan NA, Bandar A. Mitogen-induced cytokine responses of maternal peripheral blood lymphocytes indicate a differential Th-type bias in normal pregnancy and pregnancy failure. Am J Reprod Immunol 1999;42(5):273-281.
Beer AE, Kwak JY, Ruiz JE. Immunophenotypic profiles of peripheral blood lymphocytes in women with recurrent pregnancy losses and in infertile women with multiple failed in vitro fertilization cycles. Am J Reprod Immunol 1996;35(4):376-382.
Polgar K, and Hill JA. Identification of the white blood cell populations responsible for Th1 immunity to trophoblast and the timing of the response in women with recurrent pregnancy loss. Gynecol Obstet Invest 2002;53(1):59-64.
Pace D, Morrison L, Bulmer JN. Proliferative activity in endometrial stromal granulocytes throughout menstrual cycle and early pregnancy. J Clin Pathol 1989;42(1):35-39.
Ferry BL, Starkey PM, Sargent IL, Watt GM, Jackson M, Redman CW. Cell populations in the human early pregnancy decidua: natural killer activity and response to interleukin-2 of CD56-positive large granular lymphocytes. Immunology 1990;70(4):446-452.
Yamamoto T, Takahashi Y, Kase N, Mori H. Role of decidual natural killer (NK) cells in patients with missed abortion: differences between cases with normal and abnormal chromosome. Clin Exp Immunol 1999;116(3):449-452.
Aoki K, Kajiura S, Matsumoto Y, Ogasawara M, Okada S, Yagami Y, Gleicher N. Preconceptional natural-killer-cell activity as a predictor of miscarriage. Lancet 1995;345(8961):1340-1342.
Emmer PM, Nelen WL, Steegers EA, et al. Peripheral natural killer cytotoxicity and CD56+CD16+ cells increase during early pregnancy in women with a history of recurrent spontaneous abortion. Hum Reprod 2000;15(5):1163-1169.
Kwak JYH, Beaman KD, Gilman-Sachs A, et al. Upregulated expression of CD56+, CD56+/16+ ve CD19+ in peripheral blood lymphocytes in pregnant women with recurrent pregnancy losses. Am J Reprod Immunol 1995;34(2):93-99.
Yamada H, Kato HE, Kobashi G, et al. High NK cell activity in early pregnancy correlates with subsequent abortion with normal chromosomes in women with recurrent abortion. Am J Reprod Immunol 2001;46(2):132-136.
Yamamoto T, Takahashi Y, Kase N, Mori H. Proportion of CD56+3+ T cells in decidual and peripheral lymphocytes of normal pregnancy and spontaneous abortion with and without history of recurrent abortion. Am J Reprod Immunol 1999;42(6):355-360.
Clifford K, Flanagan AM, Regan L. Endometrial natural killer Immune cells and molecules in women with recurrent miscarriage: a histomorphometric study. Hum Reprod 1999;14(11):2727-2730.
Quenby S, Vince G, Farquharson R, Aplin J. Recurrent miscarriage: a defect in nature's quality control? Hum Reprod 2002;17(8):1959-1963.
Quack KC, Vassiliadou N, Pudney J, Anderson DJ, Hill JA. Leukocyte activation in the decidua of chromosomally normal and abnormal fetuses from women with recurrent abortion. Hum Reprod 2001;16(5):949-955.
Shimada S, Kato EH, Morikawa M, Iwabuchi K, Nishida R, Kishi R, Onoé K, Minakami1 H, Yamada H. No difference in natural killer or natural killer T-cell population, but aberrant T-helper cell population in the endometrium of women with repeated miscarriage. Hum Reprod 2004;19(4):1018-1024.
Michimata T, Sakai M, Miyazaki S, Ogasawara MS, Suzumori K, Aoki K, Nagata K, Saito S. Decrease of T-helper 2 and T-cytotoxic 2 cells at implantation sites occurs in unexplained recurrent spontaneous abortion with normal chromosomal content. Hum Reprod 2003;18(7):1523-1528.

Details

Primary Language

Turkish

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Semir Köse ^*
0000-0001-7621-7503
Türkiye

Serap Karaarslan Takmaz
0000-0002-3185-0505
Türkiye

Murat Ulukuş
0000-0002-1728-4797
Türkiye

Osman Zekioğlu
0000-0001-9728-4385
Türkiye

Hüseyin Yılmaz
0000-0002-7513-7285
Türkiye

Publication Date

June 28, 2019

Submission Date

September 15, 2018

Acceptance Date

November 21, 2018

Published in Issue

Year 1970 Volume: 58 Number: 2

DOI

https://doi.org/10.19161/etd.551214

IZ

https://izlik.org/JA82NT53NM

Cite

RIS / Bibtex

Vancouver

1.Semir Köse, Serap Karaarslan Takmaz, Murat Ulukuş, Osman Zekioğlu, Hüseyin Yılmaz. Spontan abortus ve istemli gebelik tahliyesi olgularında desiduada T lenfosit subgrupları ve uterin doğal öldürücü hücre sayılarının immunohistokimyasal yöntem ile karşılaştırılması. EJM. 2019 Jun. 1;58(2):170-7. doi:10.19161/etd.551214