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Multiple Non-HLA Antibodies Are Significantly Increased in Chronic Active Antibody Mediated Rejection

K. Sablik1, E. Kamburova2, D. Roelen3, H. Otten2, M. Betjes1

1Erasmus MC, Rotterdam, Netherlands, 2University Medical Center Utrecht, Utrecht, Netherlands, 3University Medical Center Leiden, Leiden, Netherlands

Meeting: 2019 American Transplant Congress

Abstract number: A188

Keywords: Antibodies, Kidney transplantation

Session Information

Session Name: Poster Session A: Kidney Chronic Antibody Mediated Rejection

Session Type: Poster Session

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.

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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 May 11, 2025.

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