Non-HLA Antibodies against Structural and Non-Structural Target in C4d Negative Antibody Mediated Rejections after Renal Transplantation
1Tumor Immunology, NIH/NCI Bethesda MD,USA, Bethesda, MD, 2Pathology, Rush University Medical Center, Chicago, IL, 3Surgery, Rush University Medical Center, Chicago, IL, 4Tumor Immunology, Rush University Medical Center, Chicago, IL
Meeting: 2019 American Transplant Congress
Abstract number: A41
Keywords: Antibodies, Autoimmunity, Histocompatibility antigens, Kidney
Session Information
Session Name: Poster Session A: B-cell / Antibody /Autoimmunity
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: According to the latest Banff’s criteria approved in 2003, antibody mediated rejections following renal transplantation are divided into 2 types namely C4d + and C4d-with the presence of donor specific antibodies. However, the cases suspicious C4d -AMR or definite C4d -AMR without detectable HLA DSAs also exist. Emerging limited research reports are indicating the potential of Non-HLA antibodies, many of them being autoantibodies, contributing towards AMR. Hence, cases where AMR is detected histologically without concurrent HLA DSAs could be either due to rare allele-specific HLA DSAs or non-HLA antibodies that are reactive to the renal allografts.
*Methods: In the present study, we analyzed serum samples from 19 patients with biopsy proven C4d+ and 36 patients with biopsy proven C4d-AMR. The sera were tested against 33 Non-HLA targets using a microbead assay system using single Non-HLA antigen coated beads on the Luminex platform using commercially reagents [One Lambda, a Thermo Fisher Scientific Brand].
*Results: As shown in the figure below, out of the 33 Non-HLA targets tested, antibodies against 4 targets were predominantly observed in patients with biopsy proven C4d-AMR: Antibodies against Vimentin [VM] and Peptidylprolyl isomerase A [PPIA] were observed in significantly higher numbers of C4d-patients compared to C4d+patients [p=02 for VM and p=0.03 for PPIA]. The other two targets towards which relatively more C4d-patients had antibodies compared to C4d+patients were Fibronectin leucine rich transmembrane protein 2 [FLRT2] and Protein tyrosine phosphatase, receptor type N [PTPRN]— the differences for these two targets did not reach statistical significance.
*Conclusions: The distinctive pathogenic mechanisms of C4d+ and C4d-AMR in terms of graft function/outcome is not deciphered. In general, the Non-HLA antibodies might account for the histologically suggestive AMR cases with no evidence of HLA DSAs. VM and FLRT2 are structural proteins and PTPRN and PPIA are intracellular proteins. The potential pathogenic mechanisms of allograft injurie against intracellular and structural proteins are likely to be different. An algorithm based on Non-HLA antibodies probably could help to start addressing the basic mechanisms of C4d- and C4d+AMR in the absence of detectible HLA DSA. Hopefully this will lead to new treatment modalities.
To cite this abstract in AMA style:
Kanangat S, Kurbegovic-Skaljic I, Cimbaluk D, Oppermann M, Jensik S, Hollinger E, Olaitan O, DeCresce R. Non-HLA Antibodies against Structural and Non-Structural Target in C4d Negative Antibody Mediated Rejections after Renal Transplantation [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/non-hla-antibodies-against-structural-and-non-structural-target-in-c4d-negative-antibody-mediated-rejections-after-renal-transplantation/. Accessed May 28, 2025.« Back to 2019 American Transplant Congress