IgG Donor-Specific Anti-Human HLA Antibody Subclasses and Kidney Allograft Antibody-Mediated Injury.
Fiche publication
Date publication
janvier 2016
Journal
Journal of the American Society of Nephrology : JASN
Auteurs
Membres identifiés du Cancéropôle Est :
Dr VERNEREY Dewi
Tous les auteurs :
Lefaucheur C, Viglietti D, Bentlejewski C, Duong van Huyen JP, Vernerey D, Aubert O, Verine J, Jouven X, Legendre C, Glotz D, Loupy A, Zeevi A
Lien Pubmed
Résumé
Antibodies may have different pathogenicities according to IgG subclass. We investigated the association between IgG subclasses of circulating anti-human HLA antibodies and antibody-mediated kidney allograft injury. Among 635 consecutive kidney transplantations performed between 2008 and 2010, we enrolled 125 patients with donor-specific anti-human HLA antibodies (DSA) detected in the first year post-transplant. We assessed DSA characteristics, including specificity, HLA class specificity, mean fluorescence intensity (MFI), C1q-binding, and IgG subclass, and graft injury phenotype at the time of sera evaluation. Overall, 51 (40.8%) patients had acute antibody-mediated rejection (aABMR), 36 (28.8%) patients had subclinical ABMR (sABMR), and 38 (30.4%) patients were ABMR-free. The MFI of the immunodominant DSA (iDSA, the DSA with the highest MFI level) was 6724±464, and 41.6% of patients had iDSA 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 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). Integrating iDSA HLA class specificity, MFI level, C1q-binding status, and IgG subclasses in a Cox survival model revealed IgG3 iDSA and C1q-binding iDSA were strongly and independently associated with allograft failure. These results suggest IgG iDSA subclasses identify distinct phenotypes of kidney allograft antibody-mediated injury.
Mots clés
Allografts, immunology, Antibody Specificity, Female, HLA Antigens, immunology, Humans, Immunoglobulin G, classification, Kidney Diseases, immunology, Kidney Transplantation, Male, Middle Aged, Postoperative Complications, immunology, Tissue Donors, Transplantation Immunology
Référence
J. Am. Soc. Nephrol.. 2016 Jan;27(1):293-304