Background: Highly sensitized candidates on the kidney transplant waitlist remain a significant challenge as current desensitization protocols have variable success rates. Improved therapies are therefore needed. APRIL/BLyS are critical survival factors for B-lymphocytes and plasma cells, the main source of alloantibody production. We examined the effect of APRIL/BLyS blockade on donor specific antibody (DSA) in a preclinical rodent model as a possible novel desensitization strategy.

Methods:C57BL/6 mice were sensitized with intraperitoneal injections of 2 x 10⁶ BALB/c splenocytes. 21 days after sensitization animals were treated with 100ug of TACI-Ig administered three times per week for an additional 21 days. B-lymphocytes and DSA of TACI-Ig treated mice were then assessed by flow cytometry.

Results: APRIL/BLyS inhibition with TACI-Ig resulted in a significant depletion of B-lymphocytes in splenic tissue compared to controls (p<0.001), Fig 1. Similar reductions in B-lymphocytes in lymph nodes were seen. Subset analyses demonstrated a reduction in mature follicular and marginal zone B-lymphocytes whereas newly formed and transitional B-lymphocytes were not significantly affected compared to controls. Importantly, T-lymphocyte flow cross-match demonstrated a significant reduction of DSA in TACI-Ig treated animals compared to controls (p<0.001), Fig 2.

Conclusions: APRIL/BLyS blockade with TACI-Ig significantly depleted B-lymphocytes and reduced DSA in this sensitized rodent model. APRIL/BLyS inhibition may be a clinically useful desensitization strategy for sensitized kidney transplant candidates.

CITATION INFORMATION: Bolt B, Wilson Schlei N, Verhoven B, Redfield R. APRIL/BLyS Inhibition Reduces Donor Specific Antibody in Sensitized Mice. Am J Transplant. 2017;17 (suppl 3).

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