P054 Unexpected quiescence of expected memory response against prior kidney allografts – Novel lessons learned from an 11 year old recipient of 3 kidney transplants

Abstract

We present an 11 yr old girl who received 3 kidney transplants (KTx). She received 1st-KTx from a living donor at age 4 due to the end-stage renal disease. She had no HLA antibodies (Ab) at pre-1st-KTx, and thus pre-tx crossmatch (XM) and donor-specific HLA antibodies (DSA) were −ve. Six weeks later, the allograft was removed due to torsion (twisting of blood vessels) and thrombosis (formation of a blood clot). The C4d staining of Tx-biopsy was −ve indicating no antibody-mediated rejection (ABMR). She was relisted for the 2nd-KTx. Two-mo post tx-nephrectomy sample revealed Abs to all 10 mismatched (MM) donor’s HLA types (and associated CREG) resulting in 97% CPRA. After a 3 yr wait, she received 2nd-KTx from a deceased donor (DD) with −ve XM and DQ8 DSA (MFI = 1961). Shortly, she developed complications by BK viremia/nephropathy and immunosuppression was reduced, which potentially increased alloimmune activation. At 2-mo post-2nd-KTx, she developed de novo DSAs directed against 4 mismatched HLAs of 2nd-KTx (1600–14600 MFI). She was treated with multiple rounds of eculizumab, plasmapheresis and IVIG until Dec. 2015, when she presented with an acute increase in serum creatinine to 8.7 mg/dL. KTx biopsy showed acute ABMR. She was relisted for 3rd-KTx on Feb. 2016 with a cPRA 100%. After 2 yr wait, she received 3rd-KTx on Feb. 2018 from a DD with −ve XM and no DSA. The 3rd donor was mismatched by 8 HLA antigens - 1 of them was a repeat-MM with 1st donor and another was repeat-MM with both 1st and 2nd donors. However, Abs to 5 mismatched HLAs of the 3rd-KTx (B8, B37, Cw6, DP2, DP4) found in the historical sera (MFIs 1000–16,000) were completely −ve in multiple sera tested during 2 mo post-3rd-KTx (Fig.). No rejection was noted. Lessons learned from this case were: A 4-yr old human immune system can recognize and respond to alloantigens, and can trigger HLA-Abs production efficiently. However, acquired memory response, an integral component of adaptive immunity is not fully developed until 11 yr of age. These findings have vital implications in pediatric KTxs. Download : Download high-res image (508KB) Download : Download full-size image