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Cytokine gene polymorphisms predict acute graft rejection following renal transplantation.

Sankaran, David, Asderakis, Argiris ORCID:, Ashraf, Shazad, Roberts, Ian S.D., Short, Colin D., Dyer, Philip A., Sinnott, Paul J. and Hutchinson, Ian V. 1999. Cytokine gene polymorphisms predict acute graft rejection following renal transplantation. Kidney International 56 (1) , pp. 281-288. 10.1046/j.1523-1755.1999.00536.x

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Background: The proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha) has been implicated in the pathogenesis of acute rejection, while animal models suggest a role for interleukin-10 (IL-10) in promoting graft survival. It has also been shown that polymorphisms in the TNFA gene promoter (position -308) and in the IL-10 gene promoter (position -1082) correlate with differential production of these cytokines in vitro. The aim of this study was to determine whether TNF-alpha and IL-10 gene polymorphisms influence the incidence and severity of acute rejection in the first six months following renal transplantation. Methods: The cytokine genotypes of 115 consecutive first cadaveric kidney allograft recipients and their donors were screened. The rejection episodes (REs) were defined clinically and confirmed histologically where possible and further classified according to severity (RS), namely steroid-resistant or responsive REs. The genotypes were then correlated with the REs and RS. Results: The recipient TNF-alpha high producer genotype and IL-10 high producer genotype were significantly associated with multiple REs (>/=2) in human leukocyte antigen (HLA)-DR mismatched transplants (P = 0.0047 and P = 0.045, respectively), whereas only the TNF-alpha high producer genotype was associated with steroid-resistant REs (P = 0.025). When recipient cytokines were analyzed together, the TNF-alpha high/IL-10 high producer genotype had the worst prognosis, whereas TNF-alpha low/IL-10 low producer genotype was protective. Conclusions: We conclude that recipient TNF-alpha and IL-10 gene polymorphisms are determinants of REs and RS following kidney transplantation. Routine screening of these gene polymorphisms may have a clinical role in identifying patients at risk of multiple REs and severe rejections.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
ISSN: 0085-2538
Date of Acceptance: 8 February 1999
Last Modified: 19 Jan 2023 14:00

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