Case Report: Emergence of de novo Donor-Specific HLA antibodies post Pneumococcal & Varicella Zoster Vaccinations in Waitlisted Renal Transplant Candidate

Abstract Introduction/Objective In renal transplant waitlisted patients, vaccination series remains to be the standard of care for infection prevention. There is a need to investigate if any of these vaccines or their adjuvant components can induce de novo donor-specific antibodies (dnDSA) against human leukocyte antigens (HLA). These novel anti-HLA antibodies in renal transplant waitlisted patients can result in a positive flow cell crossmatch (FCXM) associated with an increased risk of renal transplant rejection. Methods/Case Report We present a 59-year-old renal transplant waitlisted patient who has had multiple negative T- cell and B-cell FCXM with no detection of dnDSA at baseline. We detected de-novo anti-HLA antibodies after he received pneumococcal conjugate (Pneum-C-13) and recombinant zoster vaccine (RZV). After vaccination, FCXM was positive for both T-cells and B-cells. HLA class I antibodies (A1, 23, 24, 80; B44, 45, 76) showed a panel reactive antibody (PRA) of 51%. Epitope analysis highlighted 166DG and 166ES as shared epitopes responsible for the entire specificity. The A1 dn-DSA had a mean fluorescence intensity (MFI) of 1800 and with shared A80 epitope MFI was 15,000 contributing to the strong positivity observed in T-cell and B-cell FCXM. New onset A1, and B44 DSA predicted high risk for transplant rejection with his sibling. His planned live donor renal transplant was halted and had to instead enter the kidney-paired donor program wherein he received his transplantation after 16 months. Results (if a Case Study enter NA) NA Conclusion Allosensitization risk secondary to RZV or Pneum-C-13 vaccines or their adjuvant components in renal transplant waitlisted patients must be considered as a potential risk for transplant rejection. Future studies can utilize monitoring of HLA-specific memory B-cells to provide crucial insights into the primary mechanism of action of dn-DSA anti-HLA antibody formation and suggest interventions to mitigate this memory B-cell activation.