Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall D1
Background: FSGS is a histopathological lesion that has a 40-80% risk of recurrence o in the transplanted (tx) kidney, with increased risk of graft loss. Recent studies in recurrent FSGS (rFSGS) suggest potential roles for circulating factors such as suPAR and CD40 auto-antibody (autoAb) but the interaction of these factors and their synergy with intern αvβ3, a downstream pathway for podocyte injury, is unknown.
Methods: CD40 autoAb isolated from rFSGS (CD40autoAB/rFSGS), non-recurrent FSGS (CD40autoAb/nrFSGS) and non-FSGS patients (CD40autoAb/non-FSGS) were injected (i.v.) into C57BL/6 mice every other day for a total of 6 doses. Six hours after the last dose of CD40autoABs, recombinant human suPAR protein was given i.v. at 5 [mu]g/ml to all mice in order to analyze any additive effect of suPAR on CD40autoAb/rFSGS induced proteinuria. Urine was collected before and every day after the first injection of CD40autoAb to analyze urinary albumin and creatinine. Surface plasmon resonance (SPR) was conducted for the CD40autoAbs, suPAR and integrin αvβ3.
Results: There was an increase in proteinuria (p=0.04) with the injected CD40autoAb/rFSGS only. suPAR produced a further spike in proteinuria in the CD40autoAB/rFSGS injected animals only(p=0.004). Electron microscopy of these animals confirmed podocyte foot process fusion in the CD40autoAb/rFSGS+suPAR mice confirming the synergistic pathogenic effect of both circulating factors. Only the CD40autoAb/rFSGS had specific interactions with similar binding affinity (KD = ~26 to 84 nM) towards intern αvβ3, and RUmax values of CD40auAb/nrFSGS and CD40autoAB/no-FSGS patients were negligible.
Conclusions: CD40autoAB/rFSGS and suPAR have synergistic podocytopathic effects in vivo and SPR confirmed that suPAR exhibits specific affinity to CD40autoAb isolated only from patients with rFSGS. Further studies in human biopsy samples are underway to better elucidate the pathogenic interpretation of these findings in the context of FSGS disease.
CITATION INFORMATION: Sigdel T, Wei C, Vencenti F, Reiser J, Sarwal M. Novel Insights into the Synergism of CD40 Autoantibodies and suPAR in Kidney Transplant Patients with FSGS Recurrence. Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:Sigdel T, Wei C, Vencenti F, Reiser J, Sarwal M. Novel Insights into the Synergism of CD40 Autoantibodies and suPAR in Kidney Transplant Patients with FSGS Recurrence. [abstract]. Am J Transplant. 2017; 17 (suppl 3). https://atcmeetingabstracts.com/abstract/novel-insights-into-the-synergism-of-cd40-autoantibodies-and-supar-in-kidney-transplant-patients-with-fsgs-recurrence/. Accessed May 16, 2021.
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