Elsevier

Kidney International

Volume 56, Issue 1, July 1999, Pages 281-288
Kidney International

Dialysis – Transplantation
Cytokine gene polymorphisms predict acute graft rejection following renal transplantation

https://doi.org/10.1046/j.1523-1755.1999.00536.xGet rights and content
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Cytokine gene polymorphisms predict acute graft rejection following renal transplantation.

Background

The proinflammatory cytokine tumor necrosis factor-α (TNF-α) 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-α 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-α 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-α high producer genotype was associated with steroid-resistant REs (P = 0.025). When recipient cytokines were analyzed together, the TNF-α high/IL-10 high producer genotype had the worst prognosis, whereas TNF-α low/IL-10 low producer genotype was protective.

Conclusions

We conclude that recipient TNF-α 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.

Keywords

acute rejection
chronic renal dysfunction
graft survival
cytokines
interleukin-10
kidney transplant

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