Circulating B Cells With Memory and Antibody-Secreting Phenotypes Are Detectable in Pediatric Kidney Transplant Recipients Before the Development of Antibody-Mediated Rejection.

UNLABELLED

Development of anti-human leukocyte antigen donor-specific antibodies (DSAs) is associated with antibody-mediated rejection (AMR) and reduced allograft survival in kidney transplant recipients. Whether changes in circulating lymphocytes anticipate DSA or AMR development is unclear.

METHODS

We used time-of-flight mass cytometry to analyze prospectively collected peripheral blood mononuclear cells (PBMC) from pediatric kidney transplant recipients who developed DSA (DSA-positive recipients [DSA], n = 10). PBMC were obtained at 2 months posttransplant, 3 months before DSA development, and at DSA detection. PBMC collected at the same time points posttransplant from recipients who did not develop DSA (DSA-negative recipients [DSA], n = 11) were used as controls.

RESULTS

DSA and DSA recipients had similar baseline characteristics and comparable frequencies of total B and T cells. Within DSA recipients, there was no difference in DSA levels (mean fluorescence intensity [MFI]: 13 687 ± 4159 vs 11 375 ± 1894 in DSAAMR-positive recipients (AMR) vs DSAAMR-negative recipients (AMR), respectively; = 0.630), C1q binding (5 DSAAMR [100%] vs 4 DSAAMR [80%]; = 1.000), or C3d binding (3 DSAAMR [60%] vs 1 DSAAMR [20%]; = 0.520) between patients who developed AMR and those who did not. However, DSA patients who developed AMR (n = 5; 18.0 ± 3.6 mo post-DSA detection) had increased B cells with antibody-secreting (IgDCD27CD38; = 0.002) and memory (IgDCD27CD38; = 0.003) phenotypes compared with DSA and DSAAMR recipients at DSA detection.

CONCLUSIONS

Despite the small sample size, our comprehensive phenotypic analyses show that circulating B cells with memory and antibody-secreting phenotypes are present at DSA onset, >1 year before biopsy-proven AMR in pediatric kidney transplant recipients.