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Article ; Online: B cells and kidney transplantation: beyond antibodies.

Mehrotra, Anita / Heeger, Peter S

Journal of the American Society of Nephrology : JASN

2014 Volume 25, Issue 7, Page(s) 1373–1374

MeSH term(s)	B-Lymphocytes, Regulatory/immunology ; Female ; Humans ; Interleukin-10/immunology ; Kidney Neoplasms/immunology ; Male ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Tumor Necrosis Factor-alpha ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2014-03-07
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2014020132
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Article ; Online: Concomitant loss of regulatory T and B cells is a distinguishing immune feature of antibody-mediated rejection in kidney transplantation.

Louis, Kevin / Fadakar, Paul / Macedo, Camila / Yamada, Masaki / Lucas, Michelle / Gu, Xinyan / Zeevi, Adriana / Randhawa, Parmjeet / Lefaucheur, Carmen / Metes, Diana

Kidney international

2022 Volume 101, Issue 5, Page(s) 1003–1016

Abstract: ... dimensional flow cytometry to concomitantly profile and track the two major subsets of regulatory lymphocytes ... responsible for donor-specific antibody generation leading to antibody-mediated rejection (ABMR ... Although considerable advances have been made in understanding the cellular effector mechanisms ...

Abstract	Although considerable advances have been made in understanding the cellular effector mechanisms responsible for donor-specific antibody generation leading to antibody-mediated rejection (ABMR), the identification of cellular regulators of such immune responses is lacking. To clarify this, we used high dimensional flow cytometry to concomitantly profile and track the two major subsets of regulatory lymphocytes in blood: T regulatory (T
MeSH term(s)	Antibodies ; B-Lymphocytes ; Graft Rejection/diagnosis ; Humans ; Kidney Transplantation/adverse effects ; T-Lymphocytes, Regulatory ; Tissue Donors
Chemical Substances	Antibodies
Language	English
Publishing date	2022-01-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2021.12.027
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Zs.A 797: Show issues

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Article ; Online: Coordinated Circulating T Follicular Helper and Activated B Cell Responses Underlie the Onset of Antibody-Mediated Rejection in Kidney Transplantation.

Louis, Kevin / Macedo, Camila / Bailly, Elodie / Lau, Louis / Ramaswami, Bala / Marrari, Marilyn / Landsittel, Douglas / Chang, Alexander / Chandran, Uma / Fadakar, Paul / Yamada, Masaki / Chalasani, Geetha / Randhawa, Parmjeet / Zeevi, Adriana / Singh, Harinder / Lefaucheur, Carmen / Metes, Diana

Journal of the American Society of Nephrology : JASN

2020 Volume 31, Issue 10, Page(s) 2457–2474

Abstract: ... cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying ... of circulating T: Conclusions: Patients undergoing ABMR may benefit from monitoring and therapeutic targeting ... Background: Although antibody-mediated rejection (ABMR) has been long recognized as a leading ...

Abstract	Background: Although antibody-mediated rejection (ABMR) has been long recognized as a leading cause of allograft failure after kidney transplantation, the cellular and molecular processes underlying the induction of deleterious donor-specific antibody (DSA) responses remain poorly understood. Methods: Using high-dimensional flow cytometry, Results: There were 54 patients without DSAs; of those with DSAs, ABMR emerged in 20 patients, but not in 31 patients. We identified proliferating populations of circulating T Conclusions: Patients undergoing ABMR may benefit from monitoring and therapeutic targeting of T
MeSH term(s)	Antibody Formation/physiology ; B-Lymphocytes/physiology ; Case-Control Studies ; Cytokines/blood ; Female ; Graft Rejection/blood ; Graft Rejection/etiology ; Graft Survival ; Humans ; Isoantibodies/blood ; Kidney Failure, Chronic/blood ; Kidney Failure, Chronic/immunology ; Kidney Failure, Chronic/surgery ; Kidney Transplantation/adverse effects ; Male ; T Follicular Helper Cells/physiology
Chemical Substances	Cytokines ; Isoantibodies
Language	English
Publishing date	2020-07-28
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2020030320
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Article: Circulating B Cells With Memory and Antibody-Secreting Phenotypes Are Detectable in Pediatric Kidney Transplant Recipients Before the Development of Antibody-Mediated Rejection.

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

Transplantation direct

2019 Volume 5, Issue 9, Page(s) e481

Abstract: ... B cells with memory and antibody-secreting phenotypes are present at DSA onset, >1 year before biopsy ... with antibody-mediated rejection (AMR) and reduced allograft survival in kidney transplant recipients ... from pediatric kidney transplant recipients who developed DSA (DSA-positive recipients [DSA: Results: DSA ...

Abstract	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 Results: DSA 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.
Language	English
Publishing date	2019-08-08
Publishing country	United States
Document type	Journal Article
ISSN	2373-8731
ISSN	2373-8731
DOI	10.1097/TXD.0000000000000914
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Article ; Online: Tracking Circulating HLA-Specific IgG-Producing Memory B Cells with the B-Cell ImmunoSpot Assay.

Kervella, Delphine / Heidt, Sebastiaan / Fairchild, Robert / Todryk, Stephen / Bestard, Oriol

Methods in molecular biology (Clifton, N.J.)

2024 Volume 2768, Page(s) 201–209

Abstract: ... that the detection and measurement of memory B cells capable of secreting antibodies against donor HLA antigens ... noncompliance. These DSA are measured routinely in the serum of patients prior to transplantation mainly using ... of transplant patients prior to as well as after transplantation. Such an assay is described here. ...

Abstract	Donor-specific antibodies (DSA) against human leukocyte antigen (HLA) molecules are a major risk factor for rejection of transplanted organs (in antibody-mediated rejection [ABMR]), particularly in patients who have prior sensitization or receive insufficient immunosuppression through minimization or noncompliance. These DSA are measured routinely in the serum of patients prior to transplantation mainly using bead-based technologies or cell-based assays. However, the absence of detectable serum DSA does not always reflect the absence of sensitization or histologically defined ABMR, and so it has been proposed that the detection and measurement of memory B cells capable of secreting antibodies against donor HLA antigens could be carried out using B-cell ImmunoSpot, to better inform the degree of immune sensitization of transplant patients prior to as well as after transplantation. Such an assay is described here.
MeSH term(s)	Humans ; Isoantibodies ; Memory B Cells ; Kidney Transplantation ; Graft Rejection ; HLA Antigens ; Histocompatibility Antigens Class II ; Immunoglobulin G ; Tissue Donors ; Graft Survival
Chemical Substances	Isoantibodies ; HLA Antigens ; Histocompatibility Antigens Class II ; Immunoglobulin G
Language	English
Publishing date	2024-03-19
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-3690-9_12
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Article ; Online: Translating B cell immunology to the treatment of antibody-mediated allograft rejection.

Heeger, Peter S / Haro, Maria Carrera / Jordan, Stanley

Nature reviews. Nephrology

2024 Volume 20, Issue 4, Page(s) 218–232

Abstract: ... interactions between alloreactive T cells and B cells, and depleting alloreactive memory B cells, as well ... the cytotoxic antibody effector functions mediated by natural killer cells and the complement system, and ... as donor-specific antibody-producing plasmablasts and plasma cells. Therapies aimed at reducing ...

Abstract	Antibody-mediated rejection (AMR), including chronic AMR (cAMR), causes ~50% of kidney allograft losses each year. Despite attempts to develop well-tolerated and effective therapeutics for the management of AMR, to date, none has obtained FDA approval, thereby highlighting an urgent unmet medical need. Discoveries over the past decade from basic, translational and clinical studies of transplant recipients have provided a foundation for developing novel therapeutic approaches to preventing and treating AMR and cAMR. These interventions are aimed at reducing donor-specific antibody levels, decreasing graft injury and fibrosis, and preserving kidney function. Innovative approaches emerging from basic science findings include targeting interactions between alloreactive T cells and B cells, and depleting alloreactive memory B cells, as well as donor-specific antibody-producing plasmablasts and plasma cells. Therapies aimed at reducing the cytotoxic antibody effector functions mediated by natural killer cells and the complement system, and their associated pro-inflammatory cytokines, are also undergoing evaluation. The complexity of the pathogenesis of AMR and cAMR suggest that multiple approaches will probably be required to treat these disease processes effectively. Definitive answers await results from large, double-blind, multicentre, randomized controlled clinical trials.
MeSH term(s)	Humans ; Kidney Transplantation ; Graft Rejection/prevention & control ; Graft Rejection/drug therapy ; Transplantation, Homologous ; Immunoglobulins ; Allografts ; Randomized Controlled Trials as Topic
Chemical Substances	Immunoglobulins
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2490366-8
ISSN	1759-507X ; 1759-5061
ISSN (online)	1759-507X
ISSN	1759-5061
DOI	10.1038/s41581-023-00791-0
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Zs.A 6334: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 107: Show issues

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Article ; Online: Efficacy of 2 Doses of Rituximab on B-Cell and Antidonor Antibody and Outcomes of ABO-Incompatible Living-Donor Pediatric Kidney Transplant.

Hamasaki, Yuko / Aikawa, Atsushi / Itabashi, Yoshihiro / Muramatsu, Masaki / Hyoudou, Yoji / Shinoda, Kazunobu / Takahashi, Yusuke / Sakurabayashi, Kei / Mizutani, Toshihide / Oguchi, Hideyo / Kawamura, Takeshi / Sakai, Ken / Shishido, Seiichiro

Experimental and clinical transplantation : official journal of the Middle East Society for Organ Transplantation

2019 Volume 17, Issue Suppl 1, Page(s) 105–109

Abstract: ... B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and ... between groups.: Results: In the rituximab group, CD19- and CD20-positive B cells were depleted ... pediatric kidney transplant patients.: Materials and methods: Our study of ABO-incompatible pediatric ...

Abstract	Objectives: Rituximab treatment strategies vary in ABOincompatible pediatric kidney transplant recipients. Here, we present the efficacy of 2 doses of rituximab and subsequent outcomes in ABO-incompatible pediatric kidney transplant patients. Materials and methods: Our study of ABO-incompatible pediatric kidney transplant recipients included 21 who were pretreated with desensitization that included 2 doses of 100 mg rituximab (rituximab group) at 10 and 1 day pretransplant and 14 who received splenectomy without rituximab (splenectomy group). Both groups received immunosuppression. Basiliximab was administered during transplant and 4 days posttransplant. Double-filtration plasmapheresis and/or plasma exchange procedures were performed pretransplant in those with higher antidonor antibody titers. CD19-positive and CD20-positive B cells were measured sequentially in the rituximab group. Maximum titers of antidonor antibody pre- and posttransplant, patient and graft survival, biopsy-proven rejection, and complications/infections were compared between groups. Results: In the rituximab group, CD19- and CD20-positive B cells were depleted on transplant, persistently depleted at 3 months, and under 5% until 1 year posttransplant. Maximum titers of antidonor antibodies decreased significantly posttranplant in the rituximab (P < .001) but not in the splenectomy group (P = .174), with maximum titers posttransplant significantly lower than shown in the splenectomy group (P < .001). No rituximab patients had clinical rejection, but 5 splenectomy group patients had clinical T-cell-mediated rejection, with 2 also having antibody-mediated rejection. Six in the rituximab group had cytomegalovirus viremia but no cytomegalovirus disease; however, 5 splenectomy group recipients had cytomegalovirus disease and viremia. In the rituximab group, 3 had late-onset neutropenia. One child died of hypertrophic cardio myopathy with a functioning graft; all others survived with no failed grafts. All splenectomy group children survived, although 2 had deteriorated graft function. Conclusions: Two doses of rituximab were effective in long-term B-cell depletion to suppress antidonor antibodies. The possibility of late-onset neutropenia must be considered.
MeSH term(s)	ABO Blood-Group System/immunology ; Age Factors ; B-Lymphocytes/drug effects ; B-Lymphocytes/immunology ; Blood Group Incompatibility/immunology ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft Survival/drug effects ; Histocompatibility ; Humans ; Immunosuppressive Agents/administration & dosage ; Immunosuppressive Agents/adverse effects ; Isoantibodies/immunology ; Kidney Transplantation/adverse effects ; Kidney Transplantation/methods ; Living Donors ; Male ; Plasmapheresis ; Risk Factors ; Rituximab/administration & dosage ; Rituximab/adverse effects ; Splenectomy ; Time Factors ; Treatment Outcome
Chemical Substances	ABO Blood-Group System ; Immunosuppressive Agents ; Isoantibodies ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2019-02-19
Publishing country	Turkey
Document type	Journal Article
ZDB-ID	2396778-X
ISSN	2146-8427 ; 1304-0855
ISSN (online)	2146-8427
ISSN	1304-0855
DOI	10.6002/ect.MESOT2018.O43
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Zs.A 6632: Show issues

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Article ; Online: Balancing B cell responses to the allograft: implications for vaccination.

Crane, Clarkson / Loop, Lauren / Anterasian, Christine / Geng, Bob / Ingulli, Elizabeth

Frontiers in immunology

2022 Volume 13, Page(s) 948379

Abstract: ... present data on B cell populations and SARS-CoV-2 vaccine response rates in pediatric kidney transplant ... to transplant physicians. Antibody mediated allograft rejection remains problematic in kidney transplantation ... for antibody production. We will discuss the need to improve vaccination rates in transplant recipients and ...

Abstract	Balancing enough immunosuppression to prevent allograft rejection and yet maintaining an intact immune system to respond to vaccinations, eliminate invading pathogens or cancer cells is an ongoing challenge to transplant physicians. Antibody mediated allograft rejection remains problematic in kidney transplantation and is the most common cause of graft loss despite current immunosuppressive therapies. The goal of immunosuppressive therapies is to prevent graft rejection; however, they prevent optimal vaccine responses as well. At the center of acute and chronic antibody mediated rejection and vaccine responses is the B lymphocyte. This review will highlight the role of B cells in alloimmune responses including the dependency on T cells for antibody production. We will discuss the need to improve vaccination rates in transplant recipients and present data on B cell populations and SARS-CoV-2 vaccine response rates in pediatric kidney transplant recipients.
MeSH term(s)	Allografts ; Antibodies ; B-Lymphocytes ; COVID-19/prevention & control ; COVID-19 Vaccines ; Child ; Humans ; SARS-CoV-2 ; T-Lymphocytes ; Vaccination
Chemical Substances	Antibodies ; COVID-19 Vaccines
Language	English
Publishing date	2022-07-27
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.948379
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Article ; Online: Belatacept inhibit human B cell germinal center development in immunodeficient mice.

Samson, Chloé / Thiolat, Allan / Moktefi, Anissa / Cohen, José L / Pilon, Caroline / Grimbert, Philippe

Scientific reports

2023 Volume 13, Issue 1, Page(s) 13816

Abstract: ... including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh ... B lymphocytes. This alters the B maturation and therefore the generation of plasma cells and consequently ... of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading ...

Abstract	The humoral response mediated by alloantibodies directed against donor HLA molecules (DSAs) is one of the main causes of graft loss in kidney transplantation. Understanding the pathophysiology leading to humoral kidney rejection as the development of therapeutic tools is therefore a main objective in the field of solid organ transplantation and necessitate adapted experimental models. Among the immunosuppressive agents used in renal transplantation, belatacept, a fusion protein targeting T costimulatory molecules has shown its ability to prevent more efficiently the secretion of DSA by different mechanisms including a direct action on plasma cells but also on B lymphocytes and follicular helper T lymphocytes (Tfh) cooperation. This cellular cooperation occurs within germinal centers (GC), the seat of B lymphocytes differentiation. Here, we aimed to develop a dedicated mouse model in which human GC would be functional to study the effect of belatacept on GC formation and the ability of B lymphocytes to secrete immunoglobulin. We next demonstrate that belatacept inhibits the formation of these GCs, by inhibiting the frequency of Tfh and B lymphocytes. This alters the B maturation and therefore the generation of plasma cells and consequently, immunoglobulin secretion.
MeSH term(s)	Humans ; Animals ; Mice ; Abatacept/pharmacology ; Germinal Center ; B-Lymphocytes ; Immunosuppressive Agents/pharmacology ; Plasma Cells
Chemical Substances	Abatacept (7D0YB67S97) ; Immunosuppressive Agents
Language	English
Publishing date	2023-08-24
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-40700-w
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Article ; Online: Incidence of post-transplant hepatitis B virus reactivation with the use of kidneys from donors with resolved hepatitis B virus infection.

Journal of viral hepatitis

2022 Volume 29, Issue 11, Page(s) 976–985

Abstract: ... in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell ... for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT ... in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection ...

Abstract	Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.
MeSH term(s)	DNA, Circular ; DNA, Viral/analysis ; Hepatitis B/epidemiology ; Hepatitis B Antibodies ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Humans ; Incidence ; Kidney ; Retrospective Studies
Chemical Substances	DNA, Circular ; DNA, Viral ; Hepatitis B Antibodies ; Hepatitis B Core Antigens ; Hepatitis B Surface Antigens
Language	English
Publishing date	2022-09-07
Publishing country	England
Document type	Journal Article
ZDB-ID	1212497-7
ISSN	1365-2893 ; 1352-0504
ISSN (online)	1365-2893
ISSN	1352-0504
DOI	10.1111/jvh.13740
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