MIB-1 as a predictor of response in lung allografts with moderate acute cellular rejection

The major obstacle that long-term lung transplant recipients face is bronchiolitis obliterans. Prior episodes of acute rejection, specifically their frequency, persistence, and severity, are important predictors of bronchiolitis obliterans. Many cells contribute to the damage of acute rejection, and there is no sole cell type that can predict persistent rejection or bronchiolitis obliterans. In this study we evaluated 48 transbronchial biopsy samples from various grades of acute rejection with the proliferation marker MIB-1 and attempted to retrospectively predict response to standard corticosteroid in a subpopulation of nine responders and nine nonresponders, all with grade A3 rejection. We then characterized the proliferating cells by double labeling with MIB-1 and L26, CD3, OPD4, or KP1. Our results indicate that the proliferating cells in acute lung rejection are a heterogeneous pool of T- and B-lymphocytes, T-helper cells, macrophages, endothelial cells, and possibly parenchymal cells, and that MIB-1 is a valuable tool in the evaluation of total cellular activity in this setting. In addition, the overall proliferation rate, defined as the most intense proliferation rate regardless of location in the biopsy, closely matches the grade of acute rejection. Finally, a low lesional proliferation rate, defined as the proliferation rate at the site of perivascular inflammation diagnostic of acute rejection, is an indicator of excellent response to therapy and may have potential clinical importance.