@2024 Afarand., IRAN
ISSN: 2251-8215 Sarem Journal of Reproductive Medicine 2019;3(2):59-64
ISSN: 2251-8215 Sarem Journal of Reproductive Medicine 2019;3(2):59-64
Effect of Lymphocyte Immunotherapy on Pro-Inflammatory Th17 Related Cytokine Levels in Women with Recurrent Spontaneous Abortion
ARTICLE INFO
Article Type
Original ResearchAuthors
Zare A. (*1)Saremi A. (1)
Salehian P. (1)
Roomandeh N. (2)
Naderi M. (1)
Lashgari P. (1)
Arasteh J. (3)
Kokhaei P. (2)
(*1) Sarem Cell Research Center, Sarem Women’s Hospital, Tehran, Iran
(2) Cancer Research Center and Department of Immunology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan, Iran
(3) Department of Biology, Faculty of Basic Sciences, Central Tehran Branch, Islamic Azad University, Tehran, Iran
Correspondence
Address: Sarem Women's Hospital, End of Phase 3, Ekbatan Town, Tehran, IranPhone: +98 (21) 44670888
Fax: +98 (21) 44670885
ahadzr@gmail.com
Article History
Received: December 23, 2017Accepted: April 9, 2018
ePublished: June 15, 2019
ABSTRACT
Aims
Alterations of Th17 cells during pregnancy have a crucial role in maintenance of fetus and the high level of these cells has been observed in women with recurrent spontaneous abortion. Immunotherapy with paternal lymphocytes is one of the effective therapeutic methods for this complication. The aim of this study was to evaluate the alteration in Th17 cytokine levels in patients with recurrent abortion after lymphocyte immunotherapy.
Materials & Methods In this semi-experimental study, 30 patients referred to Sarem hospital with a history of at least three recurrent abortions in 2013 were evaluated. The levels of IL-17and IL-21 in patient serum and supernatant of cultured peripheral blood mononuclear cells were assayed before and after this treatment by using ELISA. Statistical analysis was performed with Wilcoxon test by SPSS 22.
Findings The levels of IL-17and IL-21 in patient serum after immunotherapy were significantly decreased (p<0.05). Supernatant of cultured peripheral blood mononuclear cells after immunotherapy showed a low level of IL-21 (p<0.04), while this change was not significant for interleukin 17 (p=0.13).
Conclusion Lymphocyte immunotherapy reduces the level of pro-inflammatory cytokines of Th17 cells in women with recurrent spontaneous abortion.
Materials & Methods In this semi-experimental study, 30 patients referred to Sarem hospital with a history of at least three recurrent abortions in 2013 were evaluated. The levels of IL-17and IL-21 in patient serum and supernatant of cultured peripheral blood mononuclear cells were assayed before and after this treatment by using ELISA. Statistical analysis was performed with Wilcoxon test by SPSS 22.
Findings The levels of IL-17and IL-21 in patient serum after immunotherapy were significantly decreased (p<0.05). Supernatant of cultured peripheral blood mononuclear cells after immunotherapy showed a low level of IL-21 (p<0.04), while this change was not significant for interleukin 17 (p=0.13).
Conclusion Lymphocyte immunotherapy reduces the level of pro-inflammatory cytokines of Th17 cells in women with recurrent spontaneous abortion.
CITATION LINKS
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[18]Corthay A. How do regulatory T cells work?. Scand J Immunol. 2009;70(4):326-36.
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[26]Beydoun H, Saftlas AF. Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tissue Antigens. 2005;65(2):123-35.
[27]Takeshita T. Diagnosis and treatment of recurrent miscarriage associated with immunologic disorders: Is paternal lymphocyte immunization a relic of the past?. J Nippon Med Sch. 2004;71(5):308-13.
[28]Szpakowski A, Malinowski A, Głowacka E, Wilczyński JR, Kolasa D, Dyński M, et al. The influence of paternal lymphocyte immunization on the balance of Th1/Th2 type reactivity in women with unexplained recurrent spontaneous abortion. Ginekol Pol. 2000;71(6):586-92. [Polish]
[29]Wu L, Luo LH, Zhang YX, Li Q, Xu B, Zhou GX, et al. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol. 2014;12:74.
[30]Zare A, Saremi A, Hajhashemi M, Kardar GA, Moazzeni SM, Pourpak Z, et al. Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients. J Hum Reprod Sci. 2013;6(2):147-51.
[31]Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin Chim Acta. 2011;412(9-10):702-8.
[32]Gao L, Zhang JP, Chen H, Zhang SN, Chen LB, Tan JP, et al. Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion. Genet Mol Res. 2014;13(1):1169-78.
[33]Fu B, Li X, Sun R, Tong X, Ling B, Tian Z, et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013;110(3):E231-40.
[34]Yokoo T, Takakuwa K, Ooki I, Kikuchi A, Tamura M, Tanaka K. Alteration of TH1 and TH2 cells by intracellular cytokine detection in patients with unexplained recurrent abortion before and after immunotherapy with the husband's mononuclear cells. Fertil Steril. 2006;85(5):1452-8.
[35]Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD. The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod. 2010;25(10):2591-6.
[36]Yang H, Qiu L, Chen G, Ye Z, Lü C, Lin Q. Proportional change of CD4+CD25+ regulatory T cells in decidua and peripheral blood in unexplained recurrent spontaneous abortion patients. Fertil Steril. 2008;89(3):656-61.
[37] Lee SK, Kim JY, Hur SE, Kim CJ, Na BJ, Lee M, et al. An imbalance in interleukin-17-producing T and Foxp3+ regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod. 2011;26(11):2964-71.
[38]Kim DJ, Lee SK, Kim JY, Na BJ, Hur SE, Lee M, et al. Intravenous immunoglobulin G modulates peripheral blood Th17 and Foxp3(+) regulatory T cells in pregnant women with recurrent pregnancy loss. Am J Reprod Immunol. 2014;71(5):441-50.
[39]Bansal AS, Bajardeen B, Thum MY. The basis and value of currently used immunomodulatory therapies in recurrent miscarriage. J Reprod Immunol. 2012;93(1):41-51.
[40]Gharesi Fard B, Zolghadri J, Kamali Sarvestani E. Effect of leukocyte therapy on tumor necrosis factor-alpha and interferon-gamma production in patients with recurrent spontaneous abortion. Am J Reprod Immunol. 2008;59(3):242-50.
[41] Liang P, Mo M, Li GG, Yin B, Cai J, Wu T, et al. Comprehensive analysis of peripheral blood lymphocytes in 76 women with recurrent miscarriage before and after lymphocyte immunotherapy. Am J Reprod Immunol. 2012;68(2):164-74.
[42]Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503-11.
[43]Messaoudi S, Al-Khateeb GM, Dendana M, Sater MS, Jazia KB, Nouira M, et al. Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage. Eur Cytokine Netw. 2011;22(2):123-6.
[44]Saifi B, Rezaee SA, Tajik N, Ahmadpour ME, Ashrafi M, Vakili R, et al. Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod Biomed Online. 2014;29(4):481-9.
[2]Li X, Wang B, Li Y, Wang L, Zhao X, Zhou X, et al. The Th1/Th2/Th17/Treg paradigm induced by stachydrine hydrochloride reduces uterine bleeding in RU486-induced abortion mice. J Ethnopharmacol. 2013;145(1):241-53.
[3]Christiansen OB. Reproductive immunology. Mol Immunol. 2013;55(1):8-15.
[4]Pandey MK, Rani R, Agrawal S. An update in recurrent spontaneous abortion. Arch Gynecol Obstet. 2005;272(2):95-108.
[5]Garrido-Gimenez C, Alijotas-Reig J. Recurrent miscarriage: Causes, evaluation and management. Postgrad Med J. 2015;91(1073):151-62.
[6]Sugiura-Ogasawara M, Ozaki Y, Katano K, Suzumori N, Kitaori T, Mizutani E. Abnormal embryonic karyotype is the most frequent cause of recurrent miscarriage. Hum Reprod. 2012;27(8):2297-303.
[7]Kwak-Kim J, Yang KM, Gilman-Sachs A. Recurrent pregnancy loss: A disease of inflammation and coagulation. J Obstet Gynaecol Res. 2009;35(4):609-22.
[8]Mor G, Cardenas I, Abrahams V, Guller S. Inflammation and pregnancy: The role of the immune system at the implantation site. Ann N Y Acad Sci. 2011;1221(1):80-7.
[9] 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):353-6.
[10]Bates MD, Quenby S, Takakuwa K, Johnson PM, Vince GS. Aberrant cytokine production by peripheral blood mononuclear cells in recurrent pregnancy loss?. Hum Reprod. 2002;17(9):2439-44.
[11] Saito S, Nakashima A, Shima T, Ito M. Th1/Th2/Th17 and regulatory T-cell paradigm in pregnancy. Am j Reprod Immunol. 2010;63(6):601-10.
[12]Dong C. TH17 cells in development: An updated view of their molecular identity and genetic programming. Nat Rev Immunol. 2008;8(5):337-48.
[13] Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity. 2008;28(4):454-67.
[14]Korn T, Bettelli E, Oukka M, Kuchroo VK. IL-17 and Th17 Cells. Annu Rev Immunol. 2009;27:485-517.
[15]Heidt S, Segundo DS, Chadha R, Wood KJ. The impact of Th17 cells on transplant rejection and the induction of tolerance. Curr Opin Organ Transplant. 2010;15(4):456-61.
[16]Hanidziar D, Koulmanda M. Inflammation and the balance of Treg and Th17 cells in transplant rejection and tolerance. Curr Opin Organ Transplant. 2010;15(4):411-5.
[17]Yoshida S, Haque A, Mizobuchi T, Iwata T, Chiyo M, Webb TJ, et al. Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. Am J Transplant. 2006;6(4):724-35.
[18]Corthay A. How do regulatory T cells work?. Scand J Immunol. 2009;70(4):326-36.
[19]Nakashima A, Shima T, Inada K, Ito M, Saito S. The balance of the immune system between T cells and NK cells in miscarriage. Am J Reprod Immunol. 2012;67(4):304-10.
[20]Nakashima A, Ito M, Shima T, Bac ND, Hidaka T, Saito S. Accumulation of IL-17-positive cells in decidua of inevitable abortion cases. Am J Reprod Immunol. 2010;64(1):4-11.
[21]Lee SK, Kim JY, Lee M, Gilman-Sachs A, Kwak-Kim J. Th17 and regulatory T cells in women with recurrent pregnancy loss. Am J Reprod Immunol. 2012;67(4):311-8.
[22]Fu B, Tian Z, Wei H. TH17 cells in human recurrent pregnancy loss and pre-eclampsia. Cell Mol Immunol. 2014;11(6):564-70.
[23]Pandey MK, Agrawal S. Induction of MLR-Bf and protection of fetal loss: A current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion. Int Immunopharmacol. 2004;4(2):289-98.
[24]Pandey MK, Thakur S, Agrawal S. Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion. Arch Gynecol Obstet. 2004;269(3):161-72.
[25] Ito K, Tanaka T, Tsutsumi N, Obata F, Kashiwagi N. Possible mechanisms of immunotherapy for maintaining pregnancy in recurrent spontaneous aborters: Analysis of anti-idiotypic antibodies directed against autologous T-cell receptors. Hum Reprod. 1999;14(3):650-5.
[26]Beydoun H, Saftlas AF. Association of human leucocyte antigen sharing with recurrent spontaneous abortions. Tissue Antigens. 2005;65(2):123-35.
[27]Takeshita T. Diagnosis and treatment of recurrent miscarriage associated with immunologic disorders: Is paternal lymphocyte immunization a relic of the past?. J Nippon Med Sch. 2004;71(5):308-13.
[28]Szpakowski A, Malinowski A, Głowacka E, Wilczyński JR, Kolasa D, Dyński M, et al. The influence of paternal lymphocyte immunization on the balance of Th1/Th2 type reactivity in women with unexplained recurrent spontaneous abortion. Ginekol Pol. 2000;71(6):586-92. [Polish]
[29]Wu L, Luo LH, Zhang YX, Li Q, Xu B, Zhou GX, et al. Alteration of Th17 and Treg cells in patients with unexplained recurrent spontaneous abortion before and after lymphocyte immunization therapy. Reprod Biol Endocrinol. 2014;12:74.
[30]Zare A, Saremi A, Hajhashemi M, Kardar GA, Moazzeni SM, Pourpak Z, et al. Correlation between serum zinc levels and successful immunotherapy in recurrent spontaneous abortion patients. J Hum Reprod Sci. 2013;6(2):147-51.
[31]Saini V, Arora S, Yadav A, Bhattacharjee J. Cytokines in recurrent pregnancy loss. Clin Chim Acta. 2011;412(9-10):702-8.
[32]Gao L, Zhang JP, Chen H, Zhang SN, Chen LB, Tan JP, et al. Characteristics of immune cell changes before and after immunotherapy and their clinical significance in patients with unexplained recurrent spontaneous abortion. Genet Mol Res. 2014;13(1):1169-78.
[33]Fu B, Li X, Sun R, Tong X, Ling B, Tian Z, et al. Natural killer cells promote immune tolerance by regulating inflammatory TH17 cells at the human maternal-fetal interface. Proc Natl Acad Sci U S A. 2013;110(3):E231-40.
[34]Yokoo T, Takakuwa K, Ooki I, Kikuchi A, Tamura M, Tanaka K. Alteration of TH1 and TH2 cells by intracellular cytokine detection in patients with unexplained recurrent abortion before and after immunotherapy with the husband's mononuclear cells. Fertil Steril. 2006;85(5):1452-8.
[35]Wang WJ, Hao CF, Qu QL, Wang X, Qiu LH, Lin QD. The deregulation of regulatory T cells on interleukin-17-producing T helper cells in patients with unexplained early recurrent miscarriage. Hum Reprod. 2010;25(10):2591-6.
[36]Yang H, Qiu L, Chen G, Ye Z, Lü C, Lin Q. Proportional change of CD4+CD25+ regulatory T cells in decidua and peripheral blood in unexplained recurrent spontaneous abortion patients. Fertil Steril. 2008;89(3):656-61.
[37] Lee SK, Kim JY, Hur SE, Kim CJ, Na BJ, Lee M, et al. An imbalance in interleukin-17-producing T and Foxp3+ regulatory T cells in women with idiopathic recurrent pregnancy loss. Hum Reprod. 2011;26(11):2964-71.
[38]Kim DJ, Lee SK, Kim JY, Na BJ, Hur SE, Lee M, et al. Intravenous immunoglobulin G modulates peripheral blood Th17 and Foxp3(+) regulatory T cells in pregnant women with recurrent pregnancy loss. Am J Reprod Immunol. 2014;71(5):441-50.
[39]Bansal AS, Bajardeen B, Thum MY. The basis and value of currently used immunomodulatory therapies in recurrent miscarriage. J Reprod Immunol. 2012;93(1):41-51.
[40]Gharesi Fard B, Zolghadri J, Kamali Sarvestani E. Effect of leukocyte therapy on tumor necrosis factor-alpha and interferon-gamma production in patients with recurrent spontaneous abortion. Am J Reprod Immunol. 2008;59(3):242-50.
[41] Liang P, Mo M, Li GG, Yin B, Cai J, Wu T, et al. Comprehensive analysis of peripheral blood lymphocytes in 76 women with recurrent miscarriage before and after lymphocyte immunotherapy. Am J Reprod Immunol. 2012;68(2):164-74.
[42]Liu YS, Wu L, Tong XH, Wu LM, He GP, Zhou GX, et al. Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion. Am J Reprod Immunol. 2011;65(5):503-11.
[43]Messaoudi S, Al-Khateeb GM, Dendana M, Sater MS, Jazia KB, Nouira M, et al. Genetic variations in the interleukin-21 gene and the risk of recurrent idiopathic spontaneous miscarriage. Eur Cytokine Netw. 2011;22(2):123-6.
[44]Saifi B, Rezaee SA, Tajik N, Ahmadpour ME, Ashrafi M, Vakili R, et al. Th17 cells and related cytokines in unexplained recurrent spontaneous miscarriage at the implantation window. Reprod Biomed Online. 2014;29(4):481-9.