Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

The role of cytokine polymorphisms in rejection after solid organ transplantation

Abstract

The importance of cytokines to the immune response is irrefutable. Their role in the biology of solid organ transplantation per se is also assured. Thus it is likely that subtle differences in cytokine composition, particularly at the initiation of an immune response, may have a major effect on the outcome of that response. This may be particularly relevant in solid organ transplantation, where it is possible that genetic polymorphisms which influence cytokine production may determine the outcome of a transplant. Indeed, it has been suggested that immunosuppression may be individualised on the basis of recipient or donor genotype. However, much of the early data regarding the importance of specific cytokine polymorphisms has not been reproduced, and the significance of this field remains controversial. Nonetheless, with the experience gained from earlier studies, some clear patterns for future studies are emerging.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Callard R, George AJ, Stark J Cytokines, chaos, and complexity Immunity 1999 11 507–513

    Article  CAS  Google Scholar 

  2. Altare F, Jouanguy E, Lamhamedi S, Doffinger R, Fischer A, Casanova JL Mendelian susceptibility to mycobacterial infection in man Curr Opin Immunol 1998 10 413–417

    Article  CAS  Google Scholar 

  3. Hutchinson IV, Turner D, Sankaran D, Awad M, Pravica V, Sinnott P Cytokine genotypes in allograft rejection: guidelines for immunosuppression Transplant Proc 1998 30 3991–3992

    Article  CAS  Google Scholar 

  4. Noronha IL, Eberlein-Gonska M, Hartley B, Stephens S, Cameron JS, Waldherr R In situ expression of tumor necrosis factor-alpha, interferon-gamma, and interleukin-2 receptors in renal allograft biopsies Transplantation 1992 54 1017–1024

    Article  CAS  Google Scholar 

  5. Morel D, Normand E, Lemoine C et al Tumor necrosis factor alpha in human kidney transplant rejection—analysis by in situ hybridization Transplantation 1993 55 773–777

    Article  CAS  Google Scholar 

  6. Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW Effects of a polymorphism in the human tumour necrosis factor a promoter on transcriptional activation Proc Nat Acad Sci USA 1997 94 3195–3199

    Article  CAS  Google Scholar 

  7. Abraham LJ, Kroeger KM Impact of the −308 TNF promoter polymorphism on the transcriptional regulation of the TNF gene: relevance to disease J Leukoc Biol 1999 66 562–566

    Article  CAS  Google Scholar 

  8. Knight JC, Kwiatkowski D Inherited variability of tumor necrosis factor production and susceptibility to infectious disease Proc Assoc Am Physicians 1999 111 290–298

    Article  CAS  Google Scholar 

  9. Allcock RJ, Williams JH, Price P The central MHC gene, BAT1, may encode a protein that down-regulates cytokine production Genes Cells 2001 6 487–494

    Article  CAS  Google Scholar 

  10. Knight JC, Udalova I, Hill AVS et al A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria Nat Genet 1999 22 145–150

    Article  CAS  Google Scholar 

  11. Baan CC, van Emmerik NE, Balk AH et al Cytokine mRNA expression in endomyocardial biopsies during acute rejection from human heart transplants Clin Exp Immunol 1994 97 293–298

    Article  CAS  Google Scholar 

  12. Iacono A, Dauber J, Keenan R et al Interleukin 6 and interferon-gamma gene expression in lung transplant recipients with refractory acute cellular rejection: implications for monitoring and inhibition by treatment with aerosolized cyclosporine Transplantation 1997 64 263–269

    Article  CAS  Google Scholar 

  13. McLean AG, Hughes D, Welsh KI et al Patterns of graft infiltration and cytokine gene expression during the first 10 days of kidney transplantation Transplantation 1997 63 374–380

    Article  CAS  Google Scholar 

  14. Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV An investigation of polymorphism in the interleukin-10 gene promoter Eur J Immunogenet 1997 24 1–8

    Article  CAS  Google Scholar 

  15. Moore KW, de Waal Malefyt R, Coffman RL, O’Garra A Interleukin-10 and the interleukin-10 receptor Annu Rev Immunol 2001 19 683–765

    Article  CAS  Google Scholar 

  16. Turner D, Grant SC, Yonan N et al Cytokine gene polymorphism and heart transplant rejection Transplantation 1997 64 776–779

    Article  CAS  Google Scholar 

  17. Abdallah AN, Cucchi-Mouillot P, Biteau N, Cassaigne A, Haras D, Iron A Analysis of the polymorphism of the tumour necrosis factor (TNF) gene and promoter and of circulating TNF-alpha levels in heart-transplant patients suffering or not suffering from severe rejection Eur J Immunogenet 1999 26 249–255

    Article  CAS  Google Scholar 

  18. Marshall SE, McLaren AJ, Haldar NA, Bunce M, Morris PJ, Welsh KI The impact of recipient cytokine genotype on acute rejection after renal transplantation Transplantation 2000 70 1485–1491

    Article  CAS  Google Scholar 

  19. Pelletier R, Pravica V, Perrey C et al Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation Transplantation 2000 70 674–680

    Article  CAS  Google Scholar 

  20. Tambur AR, Ortegel JW, Ben-Ari Z et al Role of cytokine gene polymorphism in hepatitis c recurrence and allograft rejection among liver transplant recipients Transplantation 2001 71 1475–1480

    Article  CAS  Google Scholar 

  21. Poole KL, Gibbs PJ, Evans PR, Sadek SA, Howell WM Influence of patient and donor cytokine genotypes on renal allograft rejection: evidence from a single centre study Transpl Immunol 2001 8 259–265

    Article  CAS  Google Scholar 

  22. Bathgate AJ, Pravica V, Perrey C et al The effect of polymorphisms in tumor necrosis factor-alpha, interleukin-10, and transforming growth factor-beta1 genes in acute hepatic allograft rejection Transplantation 2000 69 1514–1517

    Article  CAS  Google Scholar 

  23. Awad MR, Webber S, Boyle G et al The effect of cytokine gene polymorphisms on pediatric heart allograft outcome J Heart Lung Transplant 2001 20 625–230

    Article  CAS  Google Scholar 

  24. Sankaran D, Asderakis A, Ashraf S et al Cytokine gene polymorphisms predict acute graft rejection following renal transplantation Kidney Int 1999 56 281–288

    Article  CAS  Google Scholar 

  25. Bijlsma FJ, Bruggink AH, Hartman M et al No association between IL-10 promoter gene polymorphism and heart failure or rejection following cardiac transplantation Tissue Antigens 2001 57 151–153

    Article  CAS  Google Scholar 

  26. Asderakis A, Sankaran D, Dyer P et al Association of polymorphisms in the human interferon-gamma and interleukin-10 gene with acute and chronic kidney transplant outcome: the cytokine effect on transplantation Transplantation 2001 71 674–677

    Article  CAS  Google Scholar 

  27. Conti F, Breton S, Batteux F et al Defective interleukin-1 receptor antagonist production is associated with resistance of acute liver graft rejection to steroid therapy Am J Pathol 2000 157 1685–1692

    Article  CAS  Google Scholar 

  28. Marshall SE, McLaren AJ, McKinney EF et al Donor cytokine genotype influences the development of acute rejection after renal transplantation Transplantation 2001 71 469–476

    Article  CAS  Google Scholar 

  29. Fishman D, Faulds G, Jeffery R et al The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis J Clin Invest 1998 102 1369–1376

    Article  CAS  Google Scholar 

  30. Blobe GC, Schiemann WP, Lodish HF Role of transforming growth factor beta in human disease N Engl J Med 2000 342 1350–1358

    Article  CAS  Google Scholar 

  31. Grainger DJ, Heathcote K, Chiano M, Snieder H, Kemp PR, Metcalfe JC et al Genetic control of the circulating concentration of transforming growth factor type beta1 Hum Mol Genet 1999 8 93–97

    Article  CAS  Google Scholar 

  32. Cambien F, Ricard S, Troesch A et al Polymorphisms of the transforming growth factor-beta 1 gene in relation to myocardial infarction and blood pressure. The Etude Cas-Témoin del’Infarctus du Myocarde (ECTIM) Study Hypertension 1996 28 881–887

    Article  CAS  Google Scholar 

  33. Awad MR, El Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation Transplantation 1998 66 1014–1020

    Article  CAS  Google Scholar 

  34. Aziz T, Hasleton P, Hann AW, Yonan N, Deiraniya A, Hutchinson IV Transforming growth factor beta in relation to cardiac allograft vasculopathy after heart transplantation J ThoracCardiovasc Surg 2000 119 700–708

    CAS  Google Scholar 

  35. Densem CG, Hutchinson IV, Cooper A, Yonan N, Brooks NH Polymorphism of the transforming growth factor-beta 1 gene correlates with the development of coronary vasculopathy following cardiac transplantation J Heart Lung Transplant 2000 19 551–556

    Article  CAS  Google Scholar 

  36. Holweg CT, Baan CC, Balk AH et al The transforming growth factor-beta1 codon 10 gene polymorphism and accelerated graft vascular disease after clinical heart transplantation Transplantation 2001 71 1463–1467

    Article  CAS  Google Scholar 

  37. Hershey GKK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA The association of atopy with a gain-of-function mutation in the a subunit of the interleukin 4 receptor N Eng J Med 1997 337 1720

    Article  CAS  Google Scholar 

  38. Hackstein H, Kluter H, Fricke L, Hoyer J, Bein G The IL-4 receptor a-chain variant Q576R is strongly associated with decreased kidney allograft survival Tissue Antigens 1999 54 471–477

    Article  CAS  Google Scholar 

  39. Bogardus ST, Jr, Concato J, Feinstein AR. Clinical epidemiological quality in molecular genetic research: the need for methodological standards JAMA 1999 281 1919–1926

    Article  Google Scholar 

  40. Gambaro G, Anglani F, D’Angelo A Association studies of genetic polymorphisms and complex disease Lancet 2000 355 308–311

    Article  CAS  Google Scholar 

  41. Editorial Freely associating Nat Genet 1999 22 1–2

    Article  Google Scholar 

  42. Opelz G, Wujciak T, Dohler B, Scherer S, Mytilineos J HLA compatibility and organ transplant survival. Collaborative Transplant Study Rev Immunogenet 1999 1 334–342

    CAS  PubMed  Google Scholar 

  43. Takemoto SK, Terasaki PI, Gjertson DW, Cecka JM Twelve years’ experience with national sharing of HLA-matched cadaveric kidneys for transplantation N Engl J Med 2000 343 1078–1084

    Article  CAS  Google Scholar 

  44. Freeman RB, Jr, Tran CL, Mattoli J et al. Tumor necrosis factor genetic polymorphisms correlate with infections after liver transplantation Transplantation 1999 67 1005–1010

    Article  Google Scholar 

  45. Awad M, Pravica V, Perrey C et al CA repeat allele polymorphism in the first intron of the human interferon-gamma gene is associated with lung allograft fibrosis Hum Immunol 1999 60 343–346

    Article  CAS  Google Scholar 

  46. Mahoney RJ, Szatkowski MA, White BA, Leeber DA Tumor necrosis factor beta gene polymorphism and early primary kidney allograft loss Hum Immunol 1996 50 148–150

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to KI Welsh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marshall, S., Welsh, K. The role of cytokine polymorphisms in rejection after solid organ transplantation . Genes Immun 2, 297–303 (2001). https://doi.org/10.1038/sj.gene.6363795

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363795

Keywords

This article is cited by

Search

Quick links