Clinical and Experimental Reproductive Medicine

  • 제47권2호
  • /
  • Pages.122-129
  • /
  • 2020
  • /
  • 2233-8233(pISSN)
  • /
  • 2233-8241(eISSN)
대한생식의학회 (The Korean Society for Reproductive Medicine)
권호 표지
DOI QR코드

DOI QR Code

Maternal killer-cell immunoglobulin-like receptors and paternal human leukocyte antigen ligands in recurrent pregnancy loss cases in Turkey

  • 투고 : 2019.08.01
  • 심사 : 2020.01.02
  • 발행 : 2020.06.30
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: The survival of a semi-allogeneic fetus depends on several immunological mechanisms, and it has been suggested that recurrent pregnancy loss (RPL) could develop as a result of one or more immunological abnormalities. Methods: Compatibility between partners for human leukocyte antigen (HLA) genotypes and the relationships between maternal killer-cell immunoglobulin-like receptor (KIR) and paternal HLA-Bw4/Bw6 and HLA-C1/C2 supra-groups were investigated in 25 couples with RPL in comparison to healthy couples with children. HLA and KIR genotyping was performed using polymerase chain reaction with sequence-specific primers and/or sequence-specific oligonucleotides. Results: HLA class I incompatibility between partners, especially in HLA-B alleles, was more common in the RPL group (p= 0.01). HLA-C2 homozygosity was more frequent in the male partners of RPL couples than in other groups (p= 0.03). The KIR2DL5 gene frequency was significantly higher in both the female and male partners of RPL couples, whereas the KIR2DS3 gene frequency in male partners of RPL couples was significantly reduced (p= 0.03). The presence of KIR2DL3 in women with RPL was correlated with the presence of HLA-C2 alleles in their spouses (p= 0.03). Conclusion: Our data from a Turkish population suggest that male HLA-C2 homozygosity may play an important role in RPL. Additionally, an incidental match between male HLA-C2 and female HLA-C1 ligand KIR receptors might perturb the balance between activatory and inhibitory KIR-ligand interactions during pregnancy in couples affected by RPL. The roles of orphan KIR2DL5 and orphan KIR2DS3 in RPL remain obscure.

키워드

참고문헌

  1. ESHRE Guideline Group on RPL, Bender Atik R, Christiansen OB, Elson J, Kolte AM, Lewis S, et al. ESHRE guideline: recurrent pregnancy loss. Hum Reprod Open 2018;2018:hoy004. https://doi.org/10.1093/hropen/hoy004
  2. Kline JS. Very early pregnancy. Reprod Toxicol 1985;(1985):251-65.
  3. Coulam CB. Understanding the immunobiology of pregnancy and applying it to treatment of recurrent pregnancy loss. Early Pregnancy 2000;4:19-29.
  4. Christiansen OB. A fresh look at the causes and treatments of recurrent miscarriage, especially its immunological aspects. Hum Reprod Update 1996;2:271-93. https://doi.org/10.1093/humupd/2.4.271
  5. Ford HB, Schust DJ. Recurrent pregnancy loss: etiology, diagnosis, and therapy. Rev Obstet Gynecol 2009;2:76-83.
  6. Ober C. Studies of HLA, fertility and mate choice in a human isolate. Hum Reprod Update 1999;5:103-7. https://doi.org/10.1093/humupd/5.2.103
  7. Lashley LE, Haasnoot GW, Spruyt-Gerritse M, Claas FH. Selective advantage of HLA matching in successful uncomplicated oocyte donation pregnancies. J Reprod Immunol 2015;112:29-33. https://doi.org/10.1016/j.jri.2015.05.006
  8. Faulk WP, Temple A. Distribution of beta2 microglobulin and HLA in chorionic villi of human placentae. Nature 1976;262:799-802. https://doi.org/10.1038/262799a0
  9. Sargent IL, Borzychowski AM, Redman CW. NK cells and human pregnancy: an inflammatory view. Trends Immunol 2006;27:399-404. https://doi.org/10.1016/j.it.2006.06.009
  10. Moffett A, Loke C. Immunology of placentation in eutherian mammals. Nat Rev Immunol 2006;6:584-94. https://doi.org/10.1038/nri1897
  11. Moffett-King A. Natural killer cells and pregnancy. Nat Rev Immunol 2002;2:656-63. https://doi.org/10.1038/nri886
  12. McIntyre JA, Faulk WP. Recurrent spontaneous abortion in human pregnancy: results of immunogenetical, cellular, and humoral studies. Am J Reprod Immunol 1983;4:165-70. https://doi.org/10.1111/j.1600-0897.1983.tb00272.x
  13. Wagenknecht DR, Green KM, McIntyre JA. Analyses of HLA-DQ alleles in recurrent spontaneous abortion (RSA) couples. Am J Reprod Immunol 1997;37:1-6. https://doi.org/10.1111/j.1600-0897.1997.tb00186.x
  14. Sbracia M, Mastrone M, Scarpellini F, Grasso JA. Influence of histocompatibility antigens in recurrent spontaneous abortion couples and on their reproductive performances. Am J Reprod Immunol 1996;35:85-92. https://doi.org/10.1111/j.1600-0897.1996.tb00012.x
  15. Kruse C, Steffensen R, Varming K, Christiansen OB. A study of HLADR and -DQ alleles in 588 patients and 562 controls confirms that HLA-DRB1*03 is associated with recurrent miscarriage. Hum Reprod 2004;19:1215-21. https://doi.org/10.1093/humrep/deh200
  16. Shankarkumar U, Pawar A, Gaonkar P, Parasannavar D, Salvi V, Ghosh K. HLA allele associations in idiopathic recurrent spontaneous abortion patients from India. J Hum Reprod Sci 2008;1:19-24. https://doi.org/10.4103/0974-1208.39592
  17. Aagaard-Tillery KM, Silver R, Dalton J. Immunology of normal pregnancy. Semin Fetal Neonatal Med 2006;11:279-95. https://doi.org/10.1016/j.siny.2006.04.003
  18. Clarke AG, Kendall MD. The thymus in pregnancy: the interplay of neural, endocrine and immune influences. Immunol Today 1994;15:545-51. https://doi.org/10.1016/0167-5699(94)90212-7
  19. Lanier LL. NK cell recognition. Annu Rev Immunol 2005;23:225-74. https://doi.org/10.1146/annurev.immunol.23.021704.115526
  20. Kumar V, McNerney ME. A new self: MHC-class-I-independent natural-killer-cell self-tolerance. Nat Rev Immunol 2005;5:363-74. https://doi.org/10.1038/nri1603
  21. Vivier E, Anfossi N. Inhibitory NK-cell receptors on T cells: witness of the past, actors of the future. Nat Rev Immunol 2004;4:190-8. https://doi.org/10.1038/nri1306
  22. Middleton D, Curran M, Maxwell L. Natural killer cells and their receptors. Transpl Immunol 2002;10:147-64. https://doi.org/10.1016/S0966-3274(02)00062-X
  23. Parham P. MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 2005;5:201-14. https://doi.org/10.1038/nri1570
  24. Moretta L, Moretta A. Killer immunoglobulin-like receptors. Curr Opin Immunol 2004;16:626-33. https://doi.org/10.1016/j.coi.2004.07.010
  25. Moesta AK, Parham P. Diverse functionality among human NK cell receptors for the C1 epitope of HLA-C: KIR2DS2, KIR2DL2, and KIR2DL3. Front Immunol 2012;3:336.
  26. Ordonez D, Meenagh A, Gomez-Lozano N, Castano J, Middleton D, Vilches C. Duplication, mutation and recombination of the human orphan gene KIR2DS3 contribute to the diversity of KIR haplotypes. Genes Immun 2008;9:431-7. https://doi.org/10.1038/gene.2008.34
  27. Cisneros E, Moraru M, Gomez-Lozano N, Lopez-Botet M, Vilches C. KIR2DL5: an orphan inhibitory receptor displaying complex patterns of polymorphism and expression. Front Immunol 2012;3:289. https://doi.org/10.3389/fimmu.2012.00289
  28. Muller CA, Engler-Blum G, Gekeler V, Steiert I, Weiss E, Schmidt H. Genetic and serological heterogeneity of the supertypic HLA-B locus specificities Bw4 and Bw6. Immunogenetics 1989;30:200-7. https://doi.org/10.1007/BF02421207
  29. Prakash S, Sarangi AN, Alam S, Sonawane A, Sharma RK, Agrawal S. Putative role of KIR3DL1/3DS1 alleles and HLA-Bw4 ligands with end stage renal disease and long term renal allograft survival. Gene 2017;637:219-29. https://doi.org/10.1016/j.gene.2017.09.033
  30. Grifoni A, Montesano C, Patronov A, Colizzi V, Amicosante M. Immunoinformatic docking approach for the analysis of KIR3DL1/HLA-B interaction. Biomed Res Int 2013;2013:283805.
  31. Lutz CT. Human leukocyte antigen Bw4 and Bw6 epitopes recognized by antibodies and natural killer cells. Curr Opin Organ Transplant 2014;19:436-41. https://doi.org/10.1097/MOT.0000000000000103
  32. Moffett A, Chazara O, Colucci F, Johnson MH. Variation of maternal KIR and fetal HLA-C genes in reproductive failure: too early for clinical intervention. Reprod Biomed Online 2016;33:763-9. https://doi.org/10.1016/j.rbmo.2016.08.019
  33. Eksioglu Demiralp E, inventors. A method for fast and high-quality genomic or cell fee DNA isolation in a single tube and, a related kit. Turkey patent 2019/015222019-GE-44483. 2019. TURKEY patent 2019/015222019-GE-44483. 2019.
  34. Gonzalez-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, da Silva AL, et al. Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res 2015;43:D784-8. https://doi.org/10.1093/nar/gku1166
  35. Elbasi MO, Tulunay Virlan A, Eksioglu Demiralp E. Killer cell immunoglobulin-like receptor genotypes in the Turkish population. Hum Immunol 2018;79:193-4. https://doi.org/10.1016/j.humimm.2018.02.008
  36. Peakall R, Smouse PE. Genalex 6: genetic analysis in Excel. Population genetic software for teaching and research Molecular Ecology Notes 2006;6:288-95.
  37. Edwards SV, Hedrick PW. Evolution and ecology of MHC molecules: from genomics to sexual selection. Trends Ecol Evol 1998;13:305-11. https://doi.org/10.1016/S0169-5347(98)01416-5
  38. Littera R, Piredda G, Argiolas D, Lai S, Congeddu E, Ragatzu P, et al. KIR and their HLA Class I ligands: two more pieces towards completing the puzzle of chronic rejection and graft loss in kidney transplantation. PLoS One 2017;12:e0180831. https://doi.org/10.1371/journal.pone.0180831
  39. Terauchi M, Koi H, Hayano C, Toyama-Sorimachi N, Karasuyama H, Yamanashi Y, et al. Placental extravillous cytotrophoblasts persistently express class I major histocompatibility complex molecules after human cytomegalovirus infection. J Virol 2003;77:8187-95. https://doi.org/10.1128/JVI.77.15.8187-8195.2003
  40. Windsperger K, Dekan S, Pils S, Golletz C, Kunihs V, Fiala C, et al. Extravillous trophoblast invasion of venous as well as lymphatic vessels is altered in idiopathic, recurrent, spontaneous abortions. Hum Reprod 2017;32:1208-17. https://doi.org/10.1093/humrep/dex058
  41. Varla-Leftherioti M, Spyropoulou-Vlachou M, Niokou D, Keramitsoglou T, Darlamitsou A, Tsekoura C, et al. Natural killer (NK) cell receptors' repertoire in couples with recurrent spontaneous abortions. Am J Reprod Immunol 2003;49:183-91. https://doi.org/10.1034/j.1600-0897.2003.00018.x
  42. Flores AC, Marcos CY, Paladino N, Arruvito L, Williams F, Middleton D, et al. KIR receptors and HLA-C in the maintenance of pregnancy. Tissue Antigens 2007;69 Suppl 1:112-3. https://doi.org/10.1111/j.1399-0039.2006.762_8.x
  43. Sharkey AM, Gardner L, Hiby S, Farrell L, Apps R, Masters L, et al. Killer Ig-like receptor expression in uterine NK cells is biased toward recognition of HLA-C and alters with gestational age. J Immunol 2008;181:39-46. https://doi.org/10.4049/jimmunol.181.1.39
  44. Hiby SE, Walker JJ, O'shaughnessy KM, Redman CW, Carrington M, Trowsdale J, et al. Combinations of maternal KIR and fetal HLA-C genes influence the risk of preeclampsia and reproductive success. J Exp Med 2004;200:957-65. https://doi.org/10.1084/jem.20041214
  45. Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol 2010;63:425-33. https://doi.org/10.1111/j.1600-0897.2010.00836.x

피인용 문헌

  1. Killer‑cell immunoglobulin‑like receptor/human leukocyte antigen‑C combination and ‘great obstetrical syndromes’ (Review) vol.22, pp.4, 2021, https://doi.org/10.3892/etm.2021.10612