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

A. Hitz1, R. Bellmàs Sanz1, F. Ius2, J. Kühne1, B. Wiegmann2, W. Sommer2, J. Salman2, T. Siemeni2, C. Kühn2, M. Avsar2, A. Haverich2, I. Tudorache2, G. Warnecke2, C. Falk1

1Institute of Transplant Immunology, Hannover Medical School MHH, Hannover, Germany, 2Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School MHH, Hannover, Germany

Meeting: 2020 American Transplant Congress

Abstract number: C-311

Keywords: B cells, HLA antibodies, Lung preservation, Lung transplantation

Session Information

Session Name: Poster Session C: Lung: All Topics

Session Type: Poster Session

Date: Saturday, May 30, 2020

Session Time: 3:15pm-4:00pm

 Presentation Time: 3:30pm-4:00pm

Location: Virtual

*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 naïve 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 naïve 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.

*Conclusions: In the context of lung transplantation, the ratio between naïve 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.

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To cite this abstract in AMA style:

Hitz A, Sanz RBellmàs, Ius F, Kühne J, Wiegmann B, Sommer W, Salman J, Siemeni T, Kühn C, Avsar M, Haverich A, Tudorache I, Warnecke G, Falk C. 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]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-ratio-between-naive-and-memory-b-cells-is-associated-with-development-of-early-donor-specific-antibodies-within-the-first-month-after-lung-transplantation/. Accessed March 26, 2023.

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