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Marshall, Sara E.1 2; McLaren, Andrew J.; Haldar, Neil A.; Bunce, Mike; Morris, Peter J.; Welsh, Ken I.

Clinical Transplantation

Background. Acute allograft rejection remains an important cause of morbidity after kidney transplantation, and has been shown to be a crucial determinant of long-term graft function. As cytokines are major regulators of the immune system, genetic variation in cytokine production or activity may influence susceptibility to acute rejection. This study sought to determine the impact of recipient cytokine and cytokine receptor polymorphisms on acute rejection after renal transplantation.

Methods. A total of 209 cadaveric renal transplant recipients were selected for analysis according to the presence or absence of graft rejection in the first 30 days after transplantation. DNA was genotyped for 22 polymorphisms in 11 cytokine and cytokine receptor genes using the polymerase chain reaction with sequence specific primers. Results were stratified by incidence and severity of rejection, and by HLA-DR mismatching.

Results. No association between any polymorphism and the incidence or severity of acute rejection was detected. In particular, no association was seen with tumor necrosis factor or interleukin-10 genotype, either alone or in combination.

Conclusions. We have failed to demonstrate any association between recipient cytokine genotype and acute rejection after cadaveric renal transplantation. Although more extensive studies may disprove these findings, it would seem premature to use recipient cytokine genotyping to predict transplant outcome, or to guide immunosuppressive therapy after transplantation.

Oxford Transplant Centre and Nuffield Department of Surgery, Oxford Radcliffe Hospitals, Oxford, United Kingdom

Received 16 February 2000.

Accepted 24 May 2000.

2 Address correspondence to: Dr. Sara E. Marshall, Oxford Transplant Centre, Churchill Hospital, Oxford OX3 7LJ, United Kingdom.

1 Supported by a Clinician Scientist Fellowship from the Medical Research Council.

© 2000 Lippincott Williams & Wilkins, Inc.