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Abstract: TH-PO636

Renal B-Cell Activating Factor Correlates With Worsened Allograft Pathology and Inflammation in a Rat Model of Antibody-Mediated Rejection

Session Information

  • Transplantation: Basic
    November 03, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Transplantation

  • 2001 Transplantation: Basic

Authors

  • Panzer, Sarah E., University of Wisconsin-Madison, Madison, Wisconsin, United States
  • Wilson, Nancy A., University of Wisconsin-Madison, Madison, Wisconsin, United States
Background

B-cell activating factor (BAFF) promotes B cell maturation and correlates with renal disease activity in lupus nephritis. We hypothesized renal allograft BAFF levels are increased in chronic-active antibody-mediated rejection (AMR).

Methods

A minor mismatch rat kidney transplant model was utilized, with experimental groups of syngeneic, allogeneic, and sensitized allogeneic (donor blood transfusion 21 days pre-transplant) recipients. Allograft pathology and donor-specific antibody levels (DSA) were assessed 6 months post-transplant, Renal tubular epithelial cell (RTEC) and glomerular endothelial cell (GEnC) BAFF gene expression was determined, in vitro.

Results

Allogeneic and sensitized allogeneic recipients had chronic-active AMR and elevated renal BAFF levels compared to syngeneic recipients (Figure 1A). Renal BAFF correlated with glomerulitis (R2=0.39, P=0.01), peritubular capillaritis (R2=0.60, P=0.0007), microvascular inflammation (R2=0.64, P=0.0003), C4d (R2=0.43, P=0.008), intragraft macrophages (R2=0.48, P=0.004), vimentin (R2=0.46, P=0.006), and IgG DSA (R2=0.69, P=0.0001). RTEC and GEnC generated BAFF transcript in response to IFNγ stimulation, in vitro (Figure 1B).

Conclusion

Renal BAFF levels were elevated in chronic-active AMR and correlated with allograft inflammation (microvascular inflammation, intragraft macrophages, and C4d) and epithelial de-differentiation (vimentin). Thus, renal BAFF contributes to allograft inflammation and resident renal cells are a source of BAFF. As anti-BAFF therapeutics are now clinically available, further studies are needed of the effects BAFF has on renal tissues and its therapeutic effectiveness in AMR.

Figure 1. A) BAFF (red) was increased in allogeneic and sensitized allogeneic recipients compared to syngeneic recipients. B) RTEC and GEnC stimulated with IFNγ generated BAFF transcript.

Funding

  • NIDDK Support