Background. Desensitization results have largely focused on effects on anti-HLA antibody (HLA-Ab) and anti-ABO antibody levels. Anti-angiotensin II type 1 receptor antibody (AT1R-Ab) has recently been associated with allograft loss and antibody-mediated rejection and may therefore represent an important parameter to assess in desensitization. The aim of the present study was to evaluate: 1) the prevalence of AT1R-Ab in renal transplant (RTX) candidates with circulating HLA–Ab and 2) AT1R-Ab response to proteasome inhibitor (PI) desensitization therapy.

Methods. Thirty nine patients receiving PI therapy had HLA-Ab levels determined by single-antigen bead array (Luminex). Mean fluorescence intensity (MFI) of the strongest IgG HLA-Ab (immunodominant antibody -iDSA) was measured before and after PI therapy. A successful response was considered when iDSA decreased >50% at nadir versus pre-desensitization. Serum samples were also tested by ELISA for the presence of IgG AT1R-Ab (U/mL after 1:50 dilution), before and after PI-based desensitization.

Results. A high proportion of candidates with HLA-Ab exhibited AT1R-Ab (20/39, 51%). A good response of AT1R-Ab to PI therapy was observed in 18/20 patients:17.4±12.3 pre versus 10.9±13.1 U/mL post PI therapy, p=0.0009). iDSA reduction with PI desensitization was observed in 13/20 patients – 7996±2580 pre versus 4410±2695 MFI post PI therapy, p=0.0001). 12/20 patients had both iDSA and AT1R-Ab reduction by PI therapy, 6/20 to AT1R-Ab reduction only, 1/20 had iDSA but not AT1R reduction, and 1/20 patient did not experience iDSA or AT1R-Ab reduction.

AT1R-Ab levels were more elevated in Caucasians than in African-Americans both before (20.7±14.9 versus 12.3±3.7 U/mL, p=0.1), and after PI therapy (14.7±15.9 versus 5,2±2.9 U/mL, p=0.1).

Conclusions. More than half of HLA-sensitized candidates exhibit IgG AT1R-Ab. This initial desensitization experience with PI treatment consistently provided substantial reductions both in HLA-Ab and AT1R-Ab levels in an unselected, highly sensitized kidney transplant candidate population.

CITATION INFORMATION: Girnita A, Portwood E, Brailey P, Tremblay S, Alloway R, Woodle E. Anti-Angiotensin II Type 1 Receptor Antibody Reduction with Proteasome Inhibitor-Based Desensitization. Am J Transplant. 2016;16 (suppl 3).

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