Lung Transplant Recipients Developing Early DSAs within the First Month Are Characterized by a Higher Frequency of Naïve and a Lower Frequency of Memory B Cells

Abstract

<h3>Purpose</h3> 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 are treated with IgA/IgM-enriched intravenous immunoglobulins (IgGAM), in clinical AMR combined with anti-CD20 antibody (Rituximab). We hypothesize a different distribution and kinetics of IgD⁺CD27^- naïve B cells vs. IgD^-CD27^+/- memory B cell subsets in recipients with or without eDSA. <h3>Methods</h3> In a pilot study of 62 LuTx recipients, B cell subsets were by analyzed in blood pre, post (T0), 24 hours (T24) and 3 weeks after LuTx by flow cytometry using CD19, CD20, IgD, CD24, CD27, CD38 antibodies. Frequencies of B cell subsets were compared between two groups, eDSA-positive (n=14, 22,6%) and -negative (n=48, 77,4%) patients and healthy donors (n=30). <h3>Results</h3> Prior to LuTx, patients with end-stage lung disease showed significantly higher proprotions of IgD⁺CD27^- naïve B cells compared to HC (p<0.001). At T0, T1 and T24, patients with eDSAs showed significantly higher frequencies of naïve and lower frequencies of IgD^-CD27⁺ memory B cells (both p< 0.001) compared to eDSA-negative patients. These IgD⁺CD27^- naïve B cells displayed high CD24 and CD38 expression, which was stable also at 3 wks. A transient increase in IgD⁺CD27⁺ switch memory B cells was detected at T0 in both groups, returning to baseline levels at T24. <h3>Conclusion</h3> Lung transplant recipients show remarkable dynamics of naïve, memory and switch memory B cells within the first 3 wks. In both groups, we saw a shift in the B cell population: increased naïve B cells and decreased memory B cells, which was more pronounced in the eDSA group. Based on our preliminary data, a more refined B cell monitoring with additional markers 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 investigated.