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 characteristicsspecificity, class, mean fluorescence intensity (MFI), C1q-binding, and IgG subclassestogether 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, 2019.
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