TY - JOUR
T1 - Circulating B cells with memory and antibody-secreting phenotypes are detectable in pediatric kidney transplant recipients before the development of antibody-mediated rejection
AU - Fischman, Clara
AU - Fribourg, Miguel
AU - Fabrizio, Ginevri
AU - Cioni, Michela
AU - Comoli, Patrizia
AU - Nocera, Arcangelo
AU - Cardillo, Massimo
AU - Cantarelli, Chiara
AU - Gallon, Lorenzo
AU - Petrosyan, Astgik
AU - Da Sacco, Stefano
AU - Perin, Laura
AU - Cravedi, Paolo
N1 - Funding Information:
Received 10 May 2019. Accepted 16 May 2019. 1Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY. 2Nephrology, Dialysis and Transplantation Unit, IRCCS Istituto G. Gaslini, Genova, Italy. 3Pediatric Hematology/Oncology & Cell Factory, Fondazione IRCCS Policlinico S. Matteo, Pavia, Italy. 4Department Transplantation Immunology, IRCCS Fondazione Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy. 5Dipartimento di Medicina e Chirurgia Università di Parma, UO Nefrologia, Azienda Ospedaliera-Universitaria Parma, Parma, Italy. 6Department of Medicine, Division of Nephrology, Feinberg School of Medicine, Northwestern University, Chicago, IL. 7Division of Urology GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics, Children’s Hospital Los Angeles, Los Angeles, CA. C.F. and M.F. are co-first authors. L.P. and P. Cravedi are co-senior authors. This work was supported by the GOFARR Foundation and the Schenkman Family. F.C. received internal funding from the Icahn School of Medicine and NIDDK-T32 DK007757-18S1; this study was also supported by a grant from Fondazione Compagnia San Paolo to M. Cioni, and a grant from IRCCS Policlinico San Matteo, Progetti Ricerca Corrente to P. Comoli.
Publisher Copyright:
© 2019 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.
PY - 2019
Y1 - 2019
N2 - 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.
AB - 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.
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U2 - 10.1097/TXD.0000000000000914
DO - 10.1097/TXD.0000000000000914
M3 - Article
C2 - 31579809
AN - SCOPUS:85079820929
SN - 2373-8731
VL - 5
JO - Transplantation Direct
JF - Transplantation Direct
IS - 9
M1 - e481
ER -