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Title: Immunological monitoring of the B-cell compartment in renal transplant recipients
Author: Onions, Louise
ISNI:       0000 0004 5360 166X
Awarding Body: Queen Mary, University of London
Current Institution: Queen Mary, University of London
Date of Award: 2014
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B cells contribute to chronic allograft deterioration, negatively impacting graft survival, and curtailing the lifespan of a resource already in short supply. Given this, identifying alloreactive B cells could generate an important target in the battle against rejection. This study described an IgG-detecting ELISPOT used to determine if the risk of developing antibody-mediated rejection (AMR) could be predicted pretransplantation by in vitro analysis of allospecific B cells. This method failed to discriminate accurately B-cell responses to donor antigen. An alternative approach used was to detect peripheral HLA-specific B cells. Circulating HLA–A*0201 and – DQB1*0301 B cells were identified at higher frequency in sensitised patients, and this correlated with the level of serum alloantibody. Expression of HLA-DQB1*0301 B cells were at a higher frequency than HLA-A*0201 B cells in those with serum de novo donor-specific antibody (dnDSA). Next, levels of B-cell activating factor (BAFF) were investigated. Excess BAFF has been related to rejection and the development of DSA. Here elevated serum BAFF, low BAFF-receptor and DSA were all associated with deteriorating graft function. In addition intrarenal CD19+ cells, BAFF and BAFFreceptor identified with acute AMR. In contrast to a pathogenic role of B cells, a small population may be protective. The presence of regulatory B cells, defined by IL-10 production were higher in those with stable graft function, and identified with naïve B cells rather than memory B cells when compared to those with deteriorating grafts. The CD19+CD24highCD38high subset was also elevated in stable patients, and the ability to supress T-cell activation and secretion of the Th1 cell pro-inflammatory cytokine, IFN-γ was altered as a function of allograft stability. These data demonstrated characteristics within the B-cell compartment associated with stable graft function. The ability to monitor these cells may have clinical implications for predicating the risk of rejection, to dictate immunosuppressive therapy and promote allograft survival.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: Medicine