Circulating B cells with memory and antibody-secreting phenotypes are detectable in pediatric kidney transplant recipients before the development of antibody-mediated rejection

Clara Fischman, Miguel Fribourg, Ginevri Fabrizio, Michela Cioni, Patrizia Comoli, Arcangelo Nocera, Massimo Cardillo, Chiara Cantarelli, Lorenzo Gallon, Astgik Petrosyan, Stefano Da Sacco, Laura Perin, Paolo Cravedi*

*Corresponding author for this work

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Background. 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 [DSAPOS], 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 [DSANEG], n = 11) were used as controls. Results. DSAPOS and DSANEG recipients had similar baseline characteristics and comparable frequencies of total B and T cells. Within DSAPOS recipients, there was no difference in DSA levels (mean fluorescence intensity [MFI]: 13 687 ± 4159 vs 11 375 ± 1894 in DSAPOSAMR-positive recipients (AMRPOS) vs DSAPOSAMR-negative recipients (AMRNEG), respectively; P = 0.630), C1q binding (5 DSAPOSAMRPOS [100%] vs 4 DSAPOSAMRNEG [80%]; P = 1.000), or C3d binding (3 DSAPOSAMRPOS [60%] vs 1 DSAPOSAMRNEG [20%]; P = 0.520) between patients who developed AMR and those who did not. However, DSAPOS patients who developed AMR (n = 5; 18.0 ± 3.6 mo post-DSA detection) had increased B cells with antibody-secreting (IgD-CD27+CD38+; P = 0.002) and memory (IgD-CD27+CD38-; P = 0.003) phenotypes compared with DSANEG and DSAPOSAMRNEG 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.

Original languageEnglish (US)
Article numbere481
JournalTransplantation Direct
Volume5
Issue number9
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Circulating B cells with memory and antibody-secreting phenotypes are detectable in pediatric kidney transplant recipients before the development of antibody-mediated rejection'. Together they form a unique fingerprint.

  • Cite this

    Fischman, C., Fribourg, M., Fabrizio, G., Cioni, M., Comoli, P., Nocera, A., Cardillo, M., Cantarelli, C., Gallon, L., Petrosyan, A., Da Sacco, S., Perin, L., & Cravedi, P. (2019). Circulating B cells with memory and antibody-secreting phenotypes are detectable in pediatric kidney transplant recipients before the development of antibody-mediated rejection. Transplantation Direct, 5(9), [e481]. https://doi.org/10.1097/TXD.0000000000000914