Mast cell phenotypes in the allograft after lung transplantation

Background: The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MC_T) and MC-tryptase/chymase (MC_TC), after lung transplantation (LT) has not been evaluated in human studies. Methods: We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6 months post-LT, n=5), late normal allograft (>6 months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MC_T, MC_TC and MC_TCto-MC_T ratio were compared between the four groups using a generalized linear mixed model. Results: Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r²=.56, P=.009). MC_TC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MC_TC to MC_T was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). Conclusions: The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MC_TC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MC_TC in allograft dysfunction.