title: Prospective Analyses of Circulating B Cell Subsets in ABO-Compatible and ABO-Incompatible Kidney Transplant Recipients.
abstract: Immunosuppressive strategies applied in renal transplantation traditionally focus on T cell inhibition. B cells were mainly examined in the context of antibody-mediated rejection, whereas the impact of antibody-independent B cell functions has only recently entered the field of transplantation. Similar to T cells, distinct B cell subsets can enhance or inhibit immune responses. In this study, we prospectively analyzed the evolution of B cell subsets in the peripheral blood of AB0-compatible (n = 27) and AB0-incompatible (n = 10) renal transplant recipients. Activated B cells were transiently decreased and plasmablasts were permanently decreased in patients without signs of rejection throughout the first year. In patients with histologically confirmed renal allograft rejection, activated B cells and plasmablasts were significantly elevated on day 365. Rituximab treatment in AB0-incompatible patients resulted in long-lasting B cell depletion and in a naïve phenotype of repopulating B cells 1 year following transplantation. Acute allograft rejection was correlated with an increase of activated B cells and plasmablasts and with a significant reduction of regulatory B cell subsets. Our study demonstrates the remarkable effects of standard immunosuppression on circulating B cell subsets. Furthermore, the B cell compartment was significantly altered in rejecting patients. A specific targeting of deleterious B cell subsets could be of clinical benefit in renal transplantation.
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Interventional Immunology, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: H A
authors.identifier: http://orcid.org/0000-0002-1304-7719
authors.initials: HA
authors.lastname: Schlößer
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Thelen
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Dieplinger
authors.affiliation: Cologne Transplant Center, University of Cologne, Köln, Germany.|Department of Internal Medicine II, University of Cologne, Köln, Germany.
authors.forename: A
authors.initials: A
authors.lastname: von Bergwelt-Baildon
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Garcia-Marquez
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Reuter
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Shimabukuro-Vornhagen
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wennhold
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Haustein
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Buchner
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Heiermann
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kleinert
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Wahba
authors.affiliation: Institute for Clinical Transfusion Medicine, Merheim Medical Center Cologne, Köln, Germany.
authors.forename: V
authors.initials: V
authors.lastname: Ditt
authors.affiliation: Cologne Transplant Center, University of Cologne, Köln, Germany.|Department of Internal Medicine II, University of Cologne, Köln, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Kurschat
authors.affiliation: Cologne Transplant Center, University of Cologne, Köln, Germany.|Department of Internal Medicine II, University of Cologne, Köln, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Cingöz
authors.affiliation: Cologne Transplant Center, University of Cologne, Köln, Germany.|Institute of Pathology, University of Cologne, Köln, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Becker
authors.affiliation: Department of General, Visceral and Cancer Surgery, University of Cologne, Köln, Germany.|Cologne Transplant Center, University of Cologne, Köln, Germany.
authors.forename: D L
authors.initials: DL
authors.lastname: Stippel
authors.affiliation: Cologne Interventional Immunology, University of Cologne, Köln, Germany.|Department of Internal Medicine I, University of Cologne, Köln, Germany.
authors.forename: M
authors.initials: M
authors.lastname: von Bergwelt-Baildon
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D016175:B-Lymphocyte Subsets / Q000276:immunology; D001787:Blood Group Incompatibility / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000097:blood / Q000209:etiology*; D006085:Graft Survival / Q000276:immunology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects*; D019520:Living Donors; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D066027:Transplant Recipients; D014184:Transplantation, Homologous
chemical_list: D000017:ABO Blood-Group System; D007166:Immunosuppressive Agents
keywords: B cell biology; antiproliferative agent; basic (laboratory) research/science; fusion proteins and monoclonal antibodies: basiliximab/daclizumab; immunobiology; immunosuppressant; immunosuppression/immune modulation; kidney transplantation/nephrology; macrophage/monocyte biology; monitoring: immune; translational research/science