Lung Transplant Research Today is a free monthly online journal that collates and summarizes the latest research about Lung Transplant, including details on risks, prognosis, procedure, surgery, organ donation.

Innate immunity influences long-term outcomes after human lung transplant.

Palmer SM, Burch LH, Trindade AJ, Davis RD, Herczyk WF, Reinsmoen NL, Schwartz DA

Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. palme002@mc.duke.edu

RATIONALE: Lung transplantation is characterized by very high rates of acute and chronic allograft rejection. We hypothesize that activation of innate immunity augments adaptive immunity, leading to rejection after lung transplantation. In support of this idea, we have recently demonstrated that lung recipients heterozygous for either of two functional polymorphisms (Asp299Gly or Thr399Ile) in Toll-like receptor 4 (TLR4) associated with endotoxin hyporesponsiveness have decreased acute rejection over the first 6 months after transplant. OBJECTIVES: In the current analysis, we sought to extend our initial observations and investigate the effect of these TLR4 polymorphisms on post-transplant acute rejection beyond the first 6 months, bacterial infections, bronchiolitis obliterans syndrome, and survival. METHODS: Genotyping was performed on 170 lung transplant recipients. MEASUREMENTS AND MAIN RESULTS: Recipients heterozygous for either Asp299Gly or Thr399Ile had significantly reduced frequency (p = 0.02) and incidence of acute rejection (p = 0.04) sustained over 3 years after transplant, but no differences were observed in the overall onset of bronchiolitis obliterans syndrome. A trend, however, toward reduced onset of bronchiolitis obliterans syndrome grade 2 or 3 was observed in TLR4 heterozygotes. CONCLUSION: Our results demonstrate that activation of recipient innate immune responses through TLR4 has a significant and sustained effect on the development of acute lung rejection. Targeting innate immune signaling represents a promising area for future clinical studies in the prevention of lung allograft rejection.

Published 25 March 2005 in Am J Respir Crit Care Med, 171(7): 780-5.
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