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J Am Soc Nephrol. 2016 Feb;27(2):615-25. doi: 10.1681/ASN.2014040326. Epub 2015 Jun 5.

Non-Complement-Binding De Novo Donor-Specific Anti-HLA Antibodies and Kidney Allograft Survival.

Author information

1
Departments of Immunology, Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France;
2
Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and.
3
Bordeaux University, Bordeaux, France; Histopathology, Bordeaux University Hospital, Bordeaux, France;
4
Department of Medicine and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada;
5
Transplantation, Nephrology and Clinical Immunology Department, Lyon University Hospital, Lyon, France; National Institute for Health and Medical Research (INSERM) U1111, Lyon, France; Lyon Est Teaching and Research Unit, Lyon University, Lyon, France; and.
6
Histocompatibility Laboratory, French National Blood Service, Lyon, France.
7
Bordeaux University, Bordeaux, France; National Center for Scientific Research (CNRS), UMR 5164, Bordeaux, France; Nephrology-Transplantation-Dialysis, and lionel.couzi@chu-bordeaux.fr.

Abstract

C1q-binding ability may indicate the clinical relevance of de novo donor-specific anti-HLA antibodies (DSA). This study investigated the incidence and risk factors for the appearance of C1q-binding de novo DSA and their long-term impact. Using Luminex Single Antigen Flow Bead assays, 346 pretransplant nonsensitized kidney recipients were screened at 2 and 5 years after transplantation for de novo DSA, which was followed when positive by a C1q Luminex assay. At 2 and 5 years, 12 (3.5%) and eight (2.5%) patients, respectively, had C1q-binding de novo DSA. De novo DSA mean fluorescence intensity >6237 and >10,000 at 2 and 5 years, respectively, predicted C1q binding. HLA mismatches and cyclosporine A were independently associated with increased risk of C1q-binding de novo DSA. When de novo DSA were analyzed at 2 years, the 5-year death-censored graft survival was similar between patients with C1q-nonbinding de novo DSA and those without de novo DSA, but was lower for patients with C1q-binding de novo DSA (P=0.003). When de novo DSA were analyzed at 2 and 5 years, the 10-year death-censored graft survival was lower for patients with C1q-nonbinding de novo DSA detected at both 2 and 5 years (P<0.001) and for patients with C1q-binding de novo DSA (P=0.002) than for patients without de novo DSA. These results were partially confirmed in two validation cohorts. In conclusion, C1q-binding de novo DSA are associated with graft loss occurring quickly after their appearance. However, the long-term persistence of C1q-nonbinding de novo DSA could lead to lower graft survival.

KEYWORDS:

C1q; complement; de novo donor specific antibodies; graft survival; kidney transplantation

PMID:
26047793
PMCID:
PMC4731103
DOI:
10.1681/ASN.2014040326
[Indexed for MEDLINE]
Free PMC Article

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