*Purpose: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA.

*Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG measured, in addition to IgM and protective immunity. Subsequently, 60mg/kg IV was given in the setting of kidney transplantation from skin graft donors. Kidney transplant recipients received RhATG, and tacrolimus, MMF, and steroid for maintenance immunosuppression.

*Results: Circulating total IgG was reduced from a baseline 100% on D0 to 32.0% (mean, SD ± 10.6) on d4 post infusion (p<0.05), while using a donor specific antibody (DSA) assay, B-cell FXCM to 52.2±19.3% (Figure 1A). Circulating total IgM and DSA IgM were unaffected by treatment (Figure 1B). Protective immunity (anti-gB and anti-tetanoid toxin IgG) was significantly reduced for 14d post infusion (Figure 1C). Post-transplant, circulating IgG responded to anti-FcRn mAb treatment, but DSA increased rapidly (Figure 1D).

*Conclusions: Targeting the FcRn mediated recycling of IgG, is an effective means of lowering circulating donor specific IgG in the sensitized recipient, although in the setting of organ transplantation mechanisms of rapid antibody rise post-transplant remain unaffected.

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