CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation

Background. Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necess...

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Autores principales:	Emma S. Crichton, MD, MPH, Shan Zeng, MD, PhD, G. Michael La Muraglia, II, PhD, I. Raul Badell, MD
Formato:	article
Lenguaje:	EN
Publicado:	Wolters Kluwer 2021
Materias:	Surgery RD1-811
Acceso en línea:	https://doaj.org/article/944df3f4cb9c4559bf0b7959bcd41b16
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spelling	oai:doaj.org-article:944df3f4cb9c4559bf0b7959bcd41b162021-11-25T07:59:57ZCXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation2373-873110.1097/TXD.0000000000001247https://doaj.org/article/944df3f4cb9c4559bf0b7959bcd41b162021-12-01T00:00:00Zhttp://journals.lww.com/transplantationdirect/fulltext/10.1097/TXD.0000000000001247https://doaj.org/toc/2373-8731Background. Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation. Methods. A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13. Results. CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients. Conclusions. CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.Emma S. Crichton, MD, MPHShan Zeng, MD, PhDG. Michael La Muraglia, II, PhDI. Raul Badell, MDWolters KluwerarticleSurgeryRD1-811ENTransplantation Direct, Vol 7, Iss 12, p e785 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Surgery RD1-811
spellingShingle	Surgery RD1-811 Emma S. Crichton, MD, MPH Shan Zeng, MD, PhD G. Michael La Muraglia, II, PhD I. Raul Badell, MD CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
description	Background. Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation. Methods. A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13. Results. CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients. Conclusions. CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.
format	article
author	Emma S. Crichton, MD, MPH Shan Zeng, MD, PhD G. Michael La Muraglia, II, PhD I. Raul Badell, MD
author_facet	Emma S. Crichton, MD, MPH Shan Zeng, MD, PhD G. Michael La Muraglia, II, PhD I. Raul Badell, MD
author_sort	Emma S. Crichton, MD, MPH
title	CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
title_short	CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
title_full	CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
title_fullStr	CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
title_full_unstemmed	CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation
title_sort	cxcl13 is an indicator of germinal center activity and alloantibody formation following transplantation
publisher	Wolters Kluwer
publishDate	2021
url	https://doaj.org/article/944df3f4cb9c4559bf0b7959bcd41b16
work_keys_str_mv	AT emmascrichtonmdmph cxcl13isanindicatorofgerminalcenteractivityandalloantibodyformationfollowingtransplantation AT shanzengmdphd cxcl13isanindicatorofgerminalcenteractivityandalloantibodyformationfollowingtransplantation AT gmichaellamuragliaiiphd cxcl13isanindicatorofgerminalcenteractivityandalloantibodyformationfollowingtransplantation AT iraulbadellmd cxcl13isanindicatorofgerminalcenteractivityandalloantibodyformationfollowingtransplantation
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CXCL13 Is an Indicator of Germinal Center Activity and Alloantibody Formation Following Transplantation

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