Session Time: 2:30pm-4:00pm
Presentation Time: 3:42pm-3:54pm
Location: Room 615/616/617
Introduction: Antibody mediated rejection (AMR) remains a significant problem in highly sensitized individuals undergoing kidney transplantation. APRIL (A Proliferation Inducing Ligand) and BLyS (B Lymphocyte Stimulator) are critical survival factors for B lymphocytes and plasma cells, which are the primary source of alloantibody. We examined the effect of blocking APRIL/BLyS together and BLyS alone in a sensitized kidney transplant model.
Methods: c57/B6 mice were sensitized with intraperitoneal injections of BALB/c splenocytes. Following four weeks of sensitization, animals then received control Ig, BAFF-R Ig (to block BLyS alone) or TACI-Ig (to block APRIL and BLyS) for 7-10 days prior to transplantation with BALB/c kidneys. All animals were continued on treatment and received cyclosporine (10mg/kg) post-transplant. Animals were harvested on post-operative day 7. Spleen, bone marrow and lymph nodes were analyzed using flow cytometry and ELISPOT. Transplanted kidneys were analyzed via immunohistochemistry.
Results: APRIL/BLyS blockade demonstrated a significant reduction in antibody secreting B cell production of IgM and IgG in spleen and bone marrow compared to BLyS blockade alone or control Ig treatment (p<0.05). Additionally, APRIL/BLyS blockade resulted in a significant depletion of follicular B lymphocytes (CD138+IgD+) in splenocytes when compared to control Ig (p < 0.05). No significant change was noted in marginal zone B lymphocytes (CD138-IgD+). Newly formed B lymphocytes (CD138-IgD-) were decreased in animals with APRIL/BLyS blockade but was not statistically significant.
Conclusion: APRIL/BLyS blockade significantly depleted IgM and IgG production in antibody secreting B cells and decreased populations of mature B lymphocytes as seen in the follicular B lymphocytes. These findings support further studies of APRIL/BLyS blockade as a method to target alloantibody.
CITATION INFORMATION: Bath N., Ding X., Wilson N., Verhoven B., Sukhwal A., Coons L., Panzer S., Djamali A., Redfield R. APRIL/BLyS Blockade Improves Depletion of Antibody Secreting B Cells Compared to BLyS Blockade Alone in Sensitized Murine Kidney Transplant Model Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Bath N, Ding X, Wilson N, Verhoven B, Sukhwal A, Coons L, Panzer S, Djamali A, Redfield R. APRIL/BLyS Blockade Improves Depletion of Antibody Secreting B Cells Compared to BLyS Blockade Alone in Sensitized Murine Kidney Transplant Model [abstract]. https://atcmeetingabstracts.com/abstract/april-blys-blockade-improves-depletion-of-antibody-secreting-b-cells-compared-to-blys-blockade-alone-in-sensitized-murine-kidney-transplant-model/. Accessed July 16, 2019.
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