Twenty-six recipients were typed with the NcoI+/low TNF-alpha genotype, whereas 19 recipients had the NcoI-/high TNF-alpha genotype. Age, sex, donor type, secondary immunosuppression, use of anti-lymphocyte preparations, graft ischemia time, and year of transplant were evenly distributed in the two groups. There was no difference between the genotype groups in the rate of, or time to, rejection. In contrast, significantly more patients with the NcoI+/low TNF-alpha site developed infections (46% vs. 10% P=0.01). In bivari able models, each controlling for donor type, ischemia time, recipient age, use of antilymphocyte agents, and secondary immunosuppression, the NcoI+/low TNF-alpha genotype was still independently associated with increased numbers of infections (relative risk, 5.38; confidence interval, 1.20-23.8). Conclusion. We conclude that in individuals genetically predetermined to be low TNF-alpha producers, the additional inhibition of TNF-alpha production by routine immunosuppression may be excessive, rendering these individuals less able to respond to infectious stimuli. These patients may benefit from lower doses or withdrawal of corticosteroids, which are known inhibitors of TNF-alpha transcription.
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