The Role for Alloimmune and Nonalloimmune Injury and Cytokine Responses in the Pathogenesis of Bronchiolitis Obliterans Syndrome
Lung transplantation is now an effective therapeutic option for patients with many different end-stage pulmonary disorders (1,2). Although short-term survival has improved significantly since the first successful lung transplant operations, long-term outcomes remain disappointing, with five-year survival rates of only 42%, as compared to >70% for other solid organ transplantations at five years (1,2). Most late deaths are due directly or indirectly to the development of bronchiolitis obliterans syndrome (BOS), generally thought to be a manifestation of chronic lung allograft rejection (1-6). Lung transplantation is characterized by unusually high rates of allograft rejection, likely in part due to the intense recipient alloimmune and nonalloimmune responses generated to the transplanted donor lung tissue. In this chapter we focus on the two critical factors driving alloimmune [donor human leukocyte antigen (HLA)] and nonalloimmune (recipient gastroesophageal reflux) responses and highlight mechanisms by which these factors drive the production of cytokines that ultimately lead to the development of BOS.
