Impact of IgG Subclass and C1q Binding Donor-Specific HLA Antibodies on Antibody Mediated Rejection in Kidney Transplant Recipients

H. Lee¹, J. Ryu¹, S. Yun¹, T. Ban², E. Ko², C. Yang², E. Oh¹

¹Department of Laboratory Medicine, The Catholic University of Korea, Seoul, Korea, Republic of, ²Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea, Republic of

Meeting: 2019 American Transplant Congress

Abstract number: A158

Keywords: HLA antibodies, Kidney transplantation

Session Information

Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes

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: Donor specific HLA antibody (DSA) is a leading cause of antibody mediated rejection (AMR) and graft loss in kidney transplants. It is known that not all DSAs have harmful effect on allografts, and additional assays such as complement binding assay and IgG subclass analysis of DSA have been introduced. In this study, we evaluated DSA characteristics including HLA class specificity, mean fluorescence intensity (MFI), C1q-binding ability and IgG subclass, and analyzed the impact of those characteristics on AMR and histopathology of the biopsy.

*Methods: We examined DSA characteristics in 21 biopsies of patients with DSA. The presence of IgG-DSA (MFI>1000) and C1q-DSA (MFI>500) were determined using LABScreen Single Antigen kits (One Lambda) and C1qScreen assay (One lambda, USA), respectively. IgG 1-4 subclass assays were retrospectively tested using modified single antigen bead assay with replacing monoclonal secondary antibodies and sum of MFI values were analyzed. The subclass assay reagents used are in development at One Lambda.

*Results: Of the 21 DSA-positive patients [class I only (n=5), class II only (n=12), class I&II (n=4)], 18 (85.7%) patients were diagnosed as AMR (9 acute AMR and 9 chronic AMR). IgG subclass-DSAs were identified in 90.5% (19/21) of patients and 18 patients had IgG1-DSAs [IgG1 only (n=14), IgG1&IgG3 (n=2), IgG1 & IgG4 (n=2), IgG2 (n=1)]. IgG1 DSA (+) seemed to be associated with higher MFI values of total IgG-DSA (median; 10,021 vs. 5,047, P=0.070). Of 18 AMR patients, 88.9% (16/18) patients had IgG1 subclass- DSA, while 27.8% (5/18) had C1q- DSA (P < 0.001). Ten patients showed positive C4d staining on biopsy and all of them had IgG1 DSA-positive. Regarding the histologic findings, MFI values of IgG1 DSAs were associated with g+ptc (≥ 4) (1695 vs. 125, p=0.028), cg (≥1) (2782 vs. 775, P=0.011) and AMR (1303 vs. 106, P=0.027).

*Conclusions: Our results suggest that detection of IgG subclasses DSA can be helpful to identify distinct histologic phenotypes of AMR in kidney allograft biopsy. Further studies for clinical relevance of IgG1 DSA subclass are needed.

To cite this abstract in AMA style:

Lee H, Ryu J, Yun S, Ban T, Ko E, Yang C, Oh E. Impact of IgG Subclass and C1q Binding Donor-Specific HLA Antibodies on Antibody Mediated Rejection in Kidney Transplant Recipients [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/impact-of-igg-subclass-and-c1q-binding-donor-specific-hla-antibodies-on-antibody-mediated-rejection-in-kidney-transplant-recipients/. Accessed November 22, 2024.

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