Complications - 3
Nonalloimmune mechanisms contributing to lung allograft dysfunction: a potential role for gastroesophageal reflux disease. - ADDED 4/6/06 Current Opinion in Organ Transplantation. 10(3):205-210, September 2005.
Purpose of review: Lung allograft dysfunction and bronchiolitis obliterans syndrome remain the primary impediment to long-term survival after lung transplantation. Chronic aspiration resulting from gastroesophageal reflux disease is particularly common in lung transplant recipients and represents an important form of nonalloimmune injury that may initiate or exacerbate lung allograft dysfunction. Recent findings: New evidence from large retrospective studies not only corroborates that nonalloimmune injury in the form of gastroesophageal reflux disease is associated with acute rejection, bronchiolitis obliterans syndrome, and mortality, but also suggests that these sequelae can be prevented or reversed with fundoplication. More important, however, is that it is becoming clear that fundoplication is less advantageous when delayed (i.e. more than 90 days after transplant), suggesting a dose-dependent relation. Preliminary data from in-vitro studies suggest that nonalloimmune injury in lung transplant recipients with chronic aspiration involves the interaction of innate and acquired immune pathways. The details of these pathways and the extent of interaction between them have yet to be elucidated. Summary: Increasing evidence supports an important association between chronic aspiration in the context of gastroesophageal reflux disease and lung allograft dysfunction. In the future, more extensive studies in animal models and the development of prospective clinical trials will be necessary to fully elucidate this relation.
The role of the innate immune system in lung allograft rejection.- ADDED 4/4/06
Current Opinion in Organ Transplantation. 10(3):221-226, September 2005.
Purpose of review: The long-term survival after lung transplantation is limited by high rates of lung allograft rejection. Although innate immunity is central to pulmonary host defense, its role in transplantation biology has been previously unstudied. In this review the authors highlight recent studies that suggest innate immune mechanisms potentially contribute to the high rates of pulmonary allograft rejection. Recent findings: An increasing body of evidence suggests that the innate immune system critically regulates the development of allograft rejection in a number of solid organ transplants. Components of the innate immune system including both cell surface and soluble pattern recognition receptors modulate phagocytosis of pathogens, antigen presentation, and host adaptive immune responses. Polymorphisms have been identified in genes that encode components of the innate immune system leading to functional differences in innate responsiveness. This review summarizes the recent literature that implicates toll-like receptors, collectins, and defensins in the development of allograft rejection. For example, recent clinical studies suggest that genetic polymorphisms in toll-like receptor-4 associated with blunted innate immune signaling are a key determinant in long-term outcomes after lung transplant. Summary: Understanding the role of the innate immune system in the pathogenesis of acute and chronic allograft rejection after lung transplantation will enhance our understanding of transplant biology and potentially lead to the identification of new therapeutic targets. Future drugs that target novel immune pathways are critical to the development of more effective immunosuppressive strategies necessary for successful long-term lung transplant outcomes.
