Correlation between Early B and NK Cell Frequencies and in Relation to CLAD Development and PGD 24h after Lung Transplantation

Abstract

Purpose An important cause of early morbidity and mortality after lung transplantation is primary graft dysfunction (PGD). Natural killer (NK) cells are important components of the innate immunity and activated B cells could regulate the activity of innate cells. The involvement of B and NK cells in the immune reaction after lung transplantation remains incompletely understood. Neither the involvement of the innate immune reaction to the development of PGD after lung transplantation has not yet been thoroughly investigated. In this study, we aimed to investigate the correlation between early peripheral B and NK cell frequencies and the development of CLAD and PGD 24h. Methods We performed a retrospective study in 178 lung transplant recipients. The frequencies of circulating peripheral cell subsets were detected by flow cytometry at 3 weeks after transplantation. We analyzed B cells by CD19, CD27, IgM and IgG expressions, as well as the main NK cell subsets, CD56dimCD16+ vs. CD56bright CD16-. And correlated all measured cell types with CLAD development and PGD 24h. Results The cohort was divided into two groups based on CLAD development at 2 years after lung transplant and without CLAD development. Three weeks after lung transplantation, the B cell population in the CLAD-group was significantly more frequent (8.06±5.8% vs. 4.05±4.6; p=0.0009) compared to the non-CLAD-group. The patients in the non-CLAD group showed 3 weeks after lung transplantation higher proportions of CD56+CD16+ NK cells (73.09±20.4% vs. 63.78±22.3) compared to the CLAD group. In PGD24h, the B cell populations were similar (3.62±3.9% vs. 4.34±4.7). The patients in the PGD2/3 at 24h group showed 3 weeks after lung transplantation significantly higher proportions of CD56+CD16+ NK cells (5.33±4.6% vs. 3.19±2.4) compared to the PGD0/1 at 24h group. Conclusion At three weeks after lung transplantation, non-CLAD patients showed increased frequencies of CD56dimCD16+ NK cells and decreased frequencies of CD19+ B cells, indicating that a stable NK cell composition may contribute to protection from CLAD while upregulation of B cells could be an initiator of CLAD development. But it seems like that primary graft dysfunction is correlated with the activation of innate immunity, specifically CD56bright CD16- NK cells in the periphery.