Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients

Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from t...

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Published in:Journal of the American Society of Nephrology 2017-06, Vol.28 (6), p.1912-1923
Main Authors: Aubert, Olivier, Loupy, Alexandre, Hidalgo, Luis, Duong van Huyen, Jean-Paul, Higgins, Sarah, Viglietti, Denis, Jouven, Xavier, Glotz, Denis, Legendre, Christophe, Lefaucheur, Carmen, Halloran, Philip F
Format: Article
Language:English
Subjects:
Allografts
Antibodies - immunology
Antibody Specificity
Clinical Research
Female
Graft Rejection - immunology
HLA Antigens - immunology
Humans
Kidney Failure, Chronic - immunology
Kidney Failure, Chronic - surgery
Kidney Transplantation
Male
Middle Aged
Tissue Donors
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Summary:Antibody-mediated rejection (ABMR) can occur in patients with preexisting anti-HLA donor-specific antibodies (DSA) or in patients who develop DSA. However, how these processes compare in terms of allograft injury and outcome has not been addressed. From a cohort of 771 kidney biopsy specimens from two North American and five European centers, we performed a systematic assessment of clinical and biologic parameters, histopathology, circulating DSA, and allograft gene expression for all patients with ABMR ( =205). Overall, 103 (50%) patients had preexisting DSA and 102 (50%) had DSA. Compared with patients with preexisting DSA ABMR, patients with DSA ABMR displayed increased proteinuria, more transplant glomerulopathy lesions, and lower glomerulitis, but similar levels of peritubular capillaritis and C4d deposition. DSA ABMR was characterized by increased expression of IFN -inducible, natural killer cell, and T cell transcripts, but less expression of AKI transcripts compared with preexisting DSA ABMR. The preexisting DSA ABMR had superior graft survival compared with the DSA ABMR (63% versus 34% at 8 years after rejection, respectively;
ISSN:1046-6673
1533-3450
DOI:10.1681/asn.2016070797