Predictors of acute rejection after lung transplantation

Background: Acute rejection (AR) after lung transplantation (LTx) impacts survival and quality of life. The objective of this study, therefore, was to identify risk factors for AR after LTx, focusing on donor- and recipient-specific factors, operative variables, and immunologic issues, including pretransplant panel-reactive antibody (PRA) levels, and donor-recipient human leukocyte antigen (HLA) mismatch. Methods: From March 1996 to November 2007, 481 adults undergoing LTx had 3237 serial transbronchial biopsy specimens that were evaluated for perivascular rejection (grade A0 to A4). Longitudinal analysis was used to characterize the prevalence of rejection grade and influence of donor, recipient, technical, and immunologic variables. Results: AR was highest (54% < A1) in the first 2 months after LTx, decreased at 6 months (16% < A1), then remained steady. Prevalence of AR at any time was dominated by donor-specific factors of young age (p < 0.0001), blunt trauma (p = 0.008), and nonblack race (p = 0.012) and by recipient class II PRA exceeding 10% (p = 0.005). AR within 2 months was associated with HLA mismatch at the DR locus (p = 0.0006) and use of non-O blood-group donors (p = 0.008). AR at 4 years and longer after LTx was associated with HLA mismatch at the B locus (p = 0.01). Conclusions: Only a few recipient and operative factors were identified for AR after LTx. Moderately sensitized recipients identified by class II PRA exceeding 10% and those with HLA mismatches at the B and DR loci appear to be more susceptible to AR; however, such immunologic variations appear to be well controlled with current donor selection and immunosuppression protocols. The impact of donor-specific variables on AR is surprisingly strong and warrants closer inspection.