Date: Saturday, June 1, 2019
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall C & D
*Purpose: Chronic-active antibody mediated rejection (c-aABMR) is characterized by continuous inflammation at the level of the microvascular endothelium. Although donor-specific anti-HLA antibodies play an important role in this process, in many cases these antibodies cannot be detected. In recent years the presence of non-HLA antibodies has emerged as a possible prominent contributing factor in c-aABMR. We therefore investigated whether specific non-HLA antibodies are increased in patients with c-aABMR.
*Methods: Fifty-six patients with a for-cause renal biopsy showing c-aABMR (n=35) or interstitial fibrosis and tubular atrophy (IFTA) (n=21) were included between June 2015 and January 2018. Pre-transplantation sera (t=0) and sera at time of biopsy (t=1) of these patients were tested against 14 proteins highly expressed in the kidney using a multiplex non-HLA assay. The assay tested for the presence of autoantibodies against agrin, APMAP, ARHGDIB, ARHGEF6, endorepelin, AT1R, ETAR, LMNB1, LPLUNC1, PECR, Pla2R1, PRKCZ, Tubb4B, and vimentin.
*Results: A significant increase in signal-to-background-ratios (STBR) was detected over time (t=0 vs. t=1) against autoantibodies against agrin (p=0.002), ARHGEF6 (p=0.015), AT1R (p<0.001), ETAR (p=0.031), PECR (p=0.027), Tubb4B (p=0.032), vimentin (p=0.018) and ARHGDIB (p=0.011) in patients with c-aABMR. Similarly, patients with IFTA also demonstrated a significant increase in STBR for agrin, AT1R, PECR, Pla2R, Vimentin, ARHGDIB and Tubb4B autoantibodies between t=0 and t=1. However, autoantibodies against ARHGDIB, APMAP, endorepelin and Tubb4B were significantly increased at t=1 in patients with c-aABMR compared to the IFTA group. The STBR in patients with c-aABMR vs. IFTA was 3.40 vs. 1.46 (p=0.006) for anti-ARHGDIB, 1.50 vs. 1.06 (p=0.007) for anti-APMAP, 1.30 vs. 1.06 (p=0.033) for anti-endorepelin and 1.71 vs. 1.15 (p=0.007) for anti-Tubb4B.
*Conclusions: After transplantation, renal transplant patients showed a significant increase in various autoantibodies. Moveover, STBR for autoantibodies against ARHGDIB, APMAP, endorepelin and Tubb4B were significantly increased in patients with c-aABMR.
To cite this abstract in AMA style:Sablik K, Kamburova E, Roelen D, Otten H, Betjes M. Multiple Non-HLA Antibodies Are Significantly Increased in Chronic Active Antibody Mediated Rejection [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/multiple-non-hla-antibodies-are-significantly-increased-in-chronic-active-antibody-mediated-rejection/. Accessed July 10, 2020.
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