medigraphic.com
ISSN 0326-3428 (Print)
Órgano de difusión científica de la Asociación Nefrológica de Buenos Aires

2022, Number 1

<< Back Next >>

Rev Nefrol Dial Traspl 2022; 42 (1)

HLA-G and its role in solid organ transplants

Becerra RJA

Language: Spanish
References: 49
Page: 83-97
PDF size: 605.52 Kb.


ABSTRACT

Solid organ transplantation has been considered the ultimate goal for some end-stage chronic diseases, however, HLA incompatibilities between the donor and the recipient may allow the alloresponse to become deleterious for the transplanted organ, a response that can be both innate and adaptive. HLA-G y su función en trasplantes de órganos sólidos HLA-G and its role in solid organ transplants Jorge Andrés Becerra Romero HLA-G has been identified as a natural tolerance-inducing molecule (28) mainly in pregnancy and is considered a non-classical HLA class I molecule; however, it shares some structural characteristics with classic HLA. HLA-G genes are characterized by having a limited polymorphism and a cellular and tissue distribution restricted to the fetal trophoblast and thymic epithelial cells, among others. The persistent search for tolerance in organ transplants has allowed a specific study of HLA-G, as a therapeutic possibility to increase grafts and transplant patient’s survival; for this reason we carried out a review of this molecule to stimulate research and understanding of its functions.


REFERENCES

  1. Carosella ED, Rouas-Freiss N, Tronik-Le RouxD, Moreau P, LeMaoult J. HLA-G: An ImmuneCheckpoint Molecule. Adv Immunol. 2015;127:33-144. doi: 10.1016/bs.ai.2015.04.001.

  2. Hviid TV. HLA-G in human reproduction: aspects ofgenetics, function and pregnancy complications. HumReprod Update. 2006;12(3):209-32. doi: 10.1093/humupd/dmi048.

  3. Abbas AK, Lichtman AH, Pillai S. Cellular andmolecular immunology. 8th ed. Philadelphia, PA:Elsevier/Saunders, 2015. 535 p.

  4. Moreau P, Flajollet S, Carosella ED. Non-classicaltranscriptional regulation of HLA-G: an update. J CellMol Med. 2009;13(9B):2973-89. doi: 10.1111/j.1582-4934.2009.00800.x.

  5. Mouillot G, Marcou C, Zidi I, Guillard C,Sangrouber D, Carosella ED, et al. Hypoxiamodulates HLA-G gene expression in tumor cells.Hum Immunol. 2007;68(4):277-85. doi: 10.1016/j.humimm.2006.10.016.

  6. Yang JS, Li BJ, Lu HW, Chen Y, Lu C, Zhu RX, etal. Serum miR-152, miR-148a, miR-148b, and miR-21 as novel biomarkers in non-small cell lung cancerscreening. Tumour Biol. 2015;36(4):3035-42. doi:10.1007/s13277-014-2938-1.

  7. Castelli EC, Ramalho J, Porto IO, Lima TH, Felício LP,Sabbagh A, et al. Insights into HLA-G genetics providedby worldwide haplotype diversity. Front Immunol.2014;5:476. doi: 10.3389/fimmu.2014.00476.

  8. Jassem RM, Shani WS, Loisel DA, Sharief M,Billstrand C, Ober C. HLA-G polymorphismsand soluble HLA-G protein levels in women withrecurrent pregnancy loss from Basrah province in Iraq.Hum Immunol. 2012;73(8):811-7. doi: 10.1016/j.humimm.2012.05.009.

  9. Donadi EA, Castelli EC, Arnaiz-Villena A, Roger M,Rey D, Moreau P. Implications of the polymorphismof HLA-G on its function, regulation, evolution anddisease association. Cell Mol Life Sci. 2011;68(3):369-95. doi: 10.1007/s00018-010-0580-7.

  10. Castro MJ, Morales P, Martínez-Laso J, AllendeL, Rojo-Amigo R, González-Hevilla M, et al.Evolution of MHC-G in humans and primatesbased on three new 3’UT polymorphisms. HumImmunol. 2000;61(11):1157-63. doi: 10.1016/s0198-8859(00)00188-9.

  11. Le Page ME, Goodridge JP, John E, ChristiansenFT, Witt CS. Killer Ig-like receptor 2DL4 does notmediate NK cell IFN-γ responses to soluble HLA-Gpreparations. J Immunol. 2014;192(2):732-40. doi:10.4049/jimmunol.1301748.

  12. Bahri R, Hirsch F, Josse A, Rouas-Freiss N, BidereN, Vasquez A, et al. Soluble HLA-G inhibits cell cycleprogression in human alloreactive T lymphocytes.J Immunol. 2006;176(3):1331-9. doi: 10.4049/jimmunol.176.3.1331.

  13. Naji A, Menier C, Morandi F, Agaugué S, Maki G,Ferretti E, et al. Binding of HLA-G to ITIM-bearingIg-like transcript 2 receptor suppresses B cell responses.J Immunol. 2014;192(4):1536-46. doi: 10.4049/jimmunol.1300438.

  14. Apps R, Gardner L, Sharkey AM, Holmes N, MoffettA. A homodimeric complex of HLA-G on normaltrophoblast cells modulates antigen-presenting cellsvia LILRB1. Eur J Immunol. 2007;37(7):1924-37. doi:10.1002/eji.200737089.

  15. 15.) Liang S, Baibakov B, Horuzsko A. HLA-G inhibits thefunctions of murine dendritic cells via the PIR-B immuneinhibitory receptor. Eur J Immunol. 2002;32(9):2418-26. doi: 10.1002/1521-4141(200209)32:9<2418::AIDIMMU2418>3.0.CO;2-L.

  16. LeMaoult J, Krawice-Radanne I, Dausset J, CarosellaED. HLA-G1-expressing antigen-presenting cellsinduce immunosuppressive CD4+ T cells. Proc NatlAcad Sci U S A. 2004;101(18):7064-9. doi: 10.1073/pnas.0401922101.

  17. Le Rond S, Azéma C, Krawice-Radanne I, DurrbachA, Guettier C, Carosella ED, et al. Evidence to supportthe role of HLA-G5 in allograft acceptance throughinduction of immunosuppressive/ regulatory T cells.J Immunol. 2006;176(5):3266-76. doi: 10.4049/jimmunol.176.5.3266.

  18. Amodio G, Comi M, Tomasoni D, Gianolini ME,Rizzo R, LeMaoult J, et al. HLA-G expression levelsinfluence the tolerogenic activity of human DC-10.Haematologica. 2015;100(4):548-57. doi: 10.3324/haematol.2014.113803.

  19. Brown R, Kabani K, Favaloro J, Yang S, HoPJ, Gibson J, et al. CD86+ or HLA-G+ can betransferred via trogocytosis from myeloma cellsto T cells and are associated with poor prognosis.Blood. 2012;120(10):2055-63. doi: 10.1182/blood-2012-03-416792.

  20. Lila N, Carpentier A, Amrein C, Khalil-Daher I, DaussetJ, Carosella ED. Implication of HLA-G molecule inheart-graft acceptance. Lancet. 2000;355(9221):2138.doi: 10.1016/S0140-6736(00)02386-2.

  21. Bahri R, Naji A, Menier C, Charpentier B, CarosellaED, Rouas-Freiss N, et al. Dendritic cells secrete theimmunosuppressive HLA-G molecule upon CTLA4-Ig treatment: implication in human renal transplantacceptance. J Immunol. 2009;183(11):7054-62. doi:10.4049/jimmunol.0803054.

  22. Sheshgiri R, Gustafsson F, Sheedy J, Rao V, RossHJ, Delgado DH. Everolimus but not mycophenolatemofetil therapy is associated with soluble HLA-Gexpression in heart transplant patients. J Heart LungTransplant. 2009;28(11):1193-7. doi: 10.1016/j.healun.2009.07.009.

  23. Misra MK, Pandey SK, Kapoor R, Sharma RK,Kapoor R, Prakash S, et al. HLA-G gene expressioninfluenced at allelic level in association with endstage renal disease and acute allograft rejection.Hum Immunol. 2014;75(8):833-9. doi: 10.1016/j.humimm.2014.06.005.

  24. Rebmann V, da Silva Nardi F, Wagner B, Horn PA.HLA-G as a tolerogenic molecule in transplantationand pregnancy. J Immunol Res. 2014;2014:297073.doi: 10.1155/2014/297073.

  25. Capittini C, Bergamaschi P, Sachetto S, Truglio M,Viola M, Marchesi A, et al. The plasma levels of solubleHLA-G molecules correlate directly with CD34+ cellconcentration and HLA-G 14bp insertion/insertionpolymorphism in cord blood donors. Blood Transfus.2014;12(Suppl 1):s361-6. doi: 10.2450/2012.0144-12.

  26. Jacqueline Macedo Pereira J. Molécula HLA-Gy su importancia en la inmunorregulación de launidad feto-materna: aplicaciones en inmunoterapiacelular [Tesis]. Universidad Complutense de Madrid,2015. Disponible en: (consulta: ).

  27. Cervera I, Herraiz MA, Peñaloza J, Barbolla ML,Jurado ML, Macedo J, et al. Human leukocyteantigen-G allele polymorphisms have evolved followingthree different evolutionary lineages based on intronsequences. Hum Immunol. 2010;71(11):1109-15. doi:10.1016/j.humimm.2010.07.003.

  28. Rincón V, Manrique E. HLA-G: Su importanciainmunológica. Nova; 2006:4(5):91-9. doi:10.22490/24629448.352.

  29. Le Gal FA, Riteau B, Sedlik C, Khalil-Daher I, MenierC, Dausset J, et al. HLA-G-mediated inhibition ofantigen-specific cytotoxic T lymphocytes. Int Immunol.1999;11(8):1351-6. doi: 10.1093/intimm/11.8.1351.

  30. LeMaoult J, Daouya M, Wu J, Loustau M,Horuzsko A, Carosella ED. Synthetic HLA-G proteinsfor therapeutic use in transplantation. FASEB J.2013;27(9):3643-51. doi: 10.1096/fj.13-228247.

  31. Rouas-Freiss N, LeMaoult J, Moreau P, Dausset J,Carosella ED. HLA-G in transplantation: a relevantmolecule for inhibition of graft rejection? Am JTransplant. 2003;3(1):11-6. doi: 10.1034/j.1600-6143.2003.30103.x.

  32. Ferreira LMR, Meissner TB, Tilburgs T, StromingerJL. HLA-G: at the interface of maternal-fetal tolerance.Trends Immunol. 2017;38(4):272-86. doi: 10.1016/j.it.2017.01.009.

  33. Ajith A, Portik-Dobos V, Horuzsko DD, Kapoor R,Mulloy LL, et al. HLA-G and humanized mouse modelsas a novel therapeutic approach in transplantation.Hum Immunol. 2020;81(4):178-85. doi: 10.1016/j.humimm.2020.02.006.

  34. Baştürk B, Karakayali F, Emiroğlu R, Sözer O,Haberal A, Bal D, et al. Human leukocyte antigen-G, anew parameter in the follow-up of liver transplantation.Transplant Proc. 2006;38(2):571-4. doi: 10.1016/j.transproceed.2005.12.108.

  35. Ezeakile M, Portik-Dobos V, Wu J, Horuzsko DD,Kapoor R, Jagadeesan M, et al. HLA-G dimers in theprolongation of kidney allograft survival. J ImmunolRes. 2014;2014:153981. doi: 10.1155/2014/153981.

  36. Shrestha B, Haylor J, Raftery A. Historical perspectivesin kidney transplantation: an updated review. ProgTransplant. 2015;25(1):64-9, 76. doi: 10.7182/pit2015789.

  37. Sass DA, Doyle AM. Liver and kidney transplantation:a half-century historical perspective. Med ClinNorth Am. 2016;100(3):435-48. doi: 10.1016/j.mcna.2015.12.001.

  38. Becker LE, Süsal C, Morath C. Kidney transplantationacross HLA and ABO antibody barriers. Curr OpinOrgan Transplant. 2013;18(4):445-54. doi: 10.1097/MOT.0b013e3283636c20.

  39. Billingham R, Brent L, Medawar PB. Actively acquiredtolerance of foreign cells. Nature. 1953;172(4379):603-6. doi: 10.1038/172603a0.

  40. Thorsby E. A short history of HLA. TissueAntigens. 2009;74(2):101-16. doi: 10.1111/j.1399-0039.2009.01291.x.

  41. Kissmeyer-Nielsen F, Olsen S, Petersen VP, FjeldborgO. Hyperacute rejection of kidney allografts, associatedwith pre-existing humoral antibodies against donorcells. Lancet. 1966;2(7465):662-5. doi: 10.1016/s0140-6736(66)92829-7.

  42. Lafferty KJ, Cunningham AJ. A new analysis ofallogeneic interactions. Aust J Exp Biol Med Sci.1975;53(1):27-42. doi: 10.1038/icb.1975.3.

  43. Zinkernagel RM, Doherty PC. Immunologicalsurveillance against altered self componentsby sensitised T lymphocytes in lymphocyticchoriomeningitis. Nature. 1974;251(5475):547-8. doi:10.1038/251547a0.

  44. Rowntree LC, Nguyen TH, Gras S, Kotsimbos TC,Mifsud NA. Deciphering the clinical relevance of allohumanleukocyte antigen cross-reactivity in mediatingalloimmunity following transplantation. Curr OpinOrgan Transplant. 2016;21(1):29-39. doi: 10.1097/MOT.0000000000000264.

  45. Adams AB, Williams MA, Jones TR, ShirasugiN, Durham MM, Kaech SM, et al. Heterologousimmunity provides a potent barrier to transplantationtolerance. J Clin Invest. 2003;111(12):1887-95. doi:10.1172/JCI17477.

  46. Arnaiz-Villena A, Juarez I, Suarez-Trujillo F,López-Nares A, Vaquero C, Palacio-Gruber J, et al.HLA-G: function, polymorphisms and pathology. IntJ Immunogenet. 2021;48(2):172-192. doi: 10.1111/iji.12513.

  47. Pirri A, Contieri FC, Benvenutti R, Bicalho MdaG. A study of HLA-G polymorphism and linkagedisequilibrium in renal transplant patients and theirdonors. Transpl Immunol. 2009;20(3):143-9. doi:10.1016/j.trim.2008.09.012.

  48. Durmanova V, Bandzuchova H, Zilinska Z,Tirpakova J, Kuba D, Buc M, et al. Associationof HLA-G polymorphisms in the 3’UTR regionand soluble HLA-G with kidney graft outcome.Immunol Invest. 2019;48(6):644-58. doi:10.1080/08820139.2019.1610888.

  49. Janssen M, Thaiss F, Nashan B, Koch M, ThudeH. Donor derived HLA-G polymorphisms havea significant impact on acute rejection in kidneytransplantation. Hum Immunol. 2019;80(3):176-83.doi: 10.1016/j.humimm.2018.12.011.




2020     |     www.medigraphic.com