Immunoglobulin G Donor-Specific Anti-HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury

D. Viglietti,^1,2 C. Bentlejewski,³ J.-P. Duong van Huyen,^4,2 D. Vernerey,^5,2 O. Aubert,² J. Verine,¹ X. Jouven,² C. Legendre,⁴ D. Glotz,¹ A. Loupy,^2,4 A. Zeevi,³ C. Lefaucheur.^1,2

¹Saint-Louis Hospital, Paris, France
²Paris Translational Research Center for Organ Transplantation - INSERM U970, Paris, France
³University of Pittsburgh Medical Center, Pittsburgh
⁴Necker Hospital, Paris, France
⁵CHRU de Besançon, Besançon, France.

Meeting: 2015 American Transplant Congress

Abstract number: 160

Keywords: HLA antibodies, Kidney transplantation, Rejection

Session Information

Session Name: Concurrent Session: Antibodies and Graft Injury: Translational

Session Type: Concurrent Session

Date: Monday, May 4, 2015

Session Time: 2:15pm-3:45pm

Presentation Time: 2:51pm-3:03pm

Location: Room 121-AB

Experimental and clinical data suggest that antibodies have different pathogenicities according to their IgG subclasses. We investigated the association between IgG subclasses of circulating anti-HLA antibodies and antibody-mediated kidney allograft injury.

Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled patients with donor-specific anti-HLA antibodies (DSA) detected in the first year post-transplant. We assessed the DSA-positive patients for DSA characteristics—specificity, class, mean fluorescence intensity (MFI), C1q-binding, and IgG subclasses—together with the graft injury phenotype at the time of sera evaluation.

A total of 125 DSA-positive patients were included: 51 (40.8%) with acute antibody-mediated rejection (aABMR), 36 (28.8%) with sub-clinical ABMR (sABMR) and 38 (30.4%) without ABMR. The MFI of the immunodominant DSA (iDSA) was 6724±464, with 41.6% showing C1q positivity. The distribution of iDSA IgG1-4 subclasses among the population was 75.2%, 44.0%, 28.0% and 26.4%, respectively. An unsupervised principal component analysis integrating iDSA IgG subclasses revealed that aABMR was mainly driven by IgG3 iDSA, whereas sABMR was driven by IgG4 iDSA. IgG3 iDSA was associated with a shorter time to rejection (p<0.001), increased microcirculation injury (p=0.002) and C4d capillary deposition (p<0.001). IgG4 iDSA was associated with later allograft injury with increased allograft glomerulopathy and interstitial fibrosis/tubular atrophy lesions (p<0.001 for all comparisons).

When the iDSA class, MFI level, C1q-binding and IgG subclasses were integrated in a survival Cox model, IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure: hazard ratio=4.8 (p=0.003) and 3.6 (p=0.03), respectively.

The IgG DSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury. IgG3 iDSA is a strong determinant of long-term allograft failure beyond conventional DSA assessment features.

To cite this abstract in AMA style:

Viglietti D, Bentlejewski C, Huyen J-PDuongvan, Vernerey D, Aubert O, Verine J, Jouven X, Legendre C, Glotz D, Loupy A, Zeevi A, Lefaucheur C. Immunoglobulin G Donor-Specific Anti-HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/immunoglobulin-g-donor-specific-anti-hla-antibody-subclasses-and-kidney-allograft-antibody-mediated-injury/. Accessed November 21, 2024.

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