The Ratio between Naïve and Memory B Cells is Associated with Development of Early Donor-Specific Antibodies within the First Month after Lung Transplantation

Abstract

Purpose After lung transplantation (LuTx), the development of early donor HLA-specific antibodies (eDSA) has been shown to be associated with antibody-mediated rejection (AMR) and poor graft survival. Since 2013, patients with eDSA within the first month after LuTx in our center are treated with IgA/IgM enriched intravenous immunoglobulins (IgGAM), combined with anti-CD20 antibody (Rituximab). We addressed the hypothesis that naive vs. memory B cell subsets differ between eDSA-positive and negative patients already early after LuTx before onset of the treatment regimen. Methods In a pilot study of 31 out of 97 LuTx recipients in our immune monitoring cohort, B cell subsets were analysed pre, post (T0), 24h (T24) and 3 wks after LuTx. B cells were phenotyped using flow cytometry with CD19, CD27, IgD, CD24 mab. The kinetics of B cell subsets were compared between eDSA-positive (n=7) and -negative (n=24) patients. Results During the first 24h, relative B cell frequencies increased and returned to baseline at 3 wks without differences between eDSA-positive and negative LuTx patients. In eDSA-positive patients, higher frequencies of IgD+CD27-CD24hi naive and lower frequencies of IgD-CD27-CD24lo memory B cell subsets were observed constantly pre, at T0, T24 and 3wks. In contrast, a transient decrease in IgG+CD27+ switch memory B cells was detected at T0 in both groups, returning to baseline levels already at T24. Conclusion In the context of lung transplantation, the ratio between naive and memory B cells even before and directly after LuTx may be associated with the development of de novo DSA. Therefore, a refined B cell monitoring may be able to identify patients with a higher risk for eDSA development. The impact of the treatment regimen on these B cell subsets is currently further investigated in terms of differential effects on their depletion and reconstitution, respectively.