title: Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study.
abstract: Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time-dependent covariate, transitional B cell frequencies (but not total B cells or "regulatory" T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37-0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor-specific or nondonor-specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti-HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody-positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional ("regulatory") B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.
authors: Department of Nephrology and Kidney Transplantation, Queen Elizabeth Hospital Birmingham, UK; Centre for Translational Inflammation Research, University of Birmingham, UK.
authors: S
authors: S
authors: Shabir
authors: J
authors: J
authors: Girdlestone
authors: D
authors: D
authors: Briggs
authors: B
authors: B
authors: Kaul
authors: H
authors: H
authors: Smith
authors: S
authors: S
authors: Daga
authors: S
authors: S
authors: Chand
authors: S
authors: S
authors: Jham
authors: C
authors: C
authors: Navarrete
authors: L
authors: L
authors: Harper
authors: S
authors: S
authors: Ball
authors: R
authors: R
authors: Borrows
mesh_terms: D000328:Adult; D000906:Antibodies / Q000737:chemistry; D001402:B-Lymphocytes / Q000166:cytology*; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D005260:Female; D006084:Graft Rejection; D006680:HLA Antigens / Q000737:chemistry; D006801:Humans; D056724:Immunity, Humoral; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D010641:Phenotype; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000601:surgery*; D013997:Time Factors; D066027:Transplant Recipients; D023001:Transplantation Tolerance; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents
keywords: kidney disease: immune / inflammatory; kidney transplantation / nephrology; rejection: acute; rejection: antibody-mediated (ABMR); translational research / science