Transitional B Lymphocytes Are Associated With Protection From Kidney Allograft Rejection: A Prospective Study. Issue 5 (23rd March 2015)

• Record Type: Journal Article
• Authors: Shabir, S.; Girdlestone, J.; Briggs, D.; Kaul, B.; Smith, H.; Daga, S.; Chand, S.; Jham, S.; Navarrete, C.; Harper, L.; Ball, S.; Borrows, R.
• Is Part Of: American journal of transplantation. Volume 15:Issue 5(2015:May)
• Page Start: 1384
• Page End: 1391
• Publication Date: 2015-03-23
• Subjects: translational research / science -- kidney transplantation / nephrology -- kidney disease: immune / inflammatory -- rejection: acute -- rejection: antibody‐mediated (ABMR); Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.13122
• Languages: English
• ISSNs: 1600-6135

Abstract

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. Abstract : This prospective study demonstrates that transitional B lymphocytes, previously suggested to display regulatory properties and associated with transplant tolerance, are associated with freedom from rejection following kidney transplantation.