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Transplantation. 2017 Mar;101(3):631-641. doi: 10.1097/TP.0000000000001195.

Diagnostic Contribution of Donor-Specific Antibody Characteristics to Uncover Late Silent Antibody-Mediated Rejection-Results of a Cross-Sectional Screening Study.

Author information

1
1 Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria. 2 Alberta Transplant Applied Genomics Centre, ATAGC, University of Alberta, Edmonton, AB, Canada. 3 Department of Clinical Pathology, Medical University Vienna, Vienna, Austria. 4 Department of Laboratory Medicine, Medical University Vienna, Vienna, Austria. 5 Center for Medical Statistics, Informatics and Intelligent Systems, Medical University Vienna, Vienna, Austria. 6 Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB, Canada. 7 Division of Nephrology and Transplant Immunology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.

Abstract

BACKGROUND:

Circulating donor-specific antibodies (DSA) detected on bead arrays may not inevitably indicate ongoing antibody-mediated rejection (AMR). Here, we investigated whether detection of complement-fixation, in parallel to IgG mean fluorescence intensity (MFI), allows for improved prediction of AMR.

METHODS:

Our study included 86 DSA+ kidney transplant recipients subjected to protocol biopsy, who were identified upon cross-sectional antibody screening of 741 recipients with stable graft function at 6 months or longer after transplantation. IgG MFI was analyzed after elimination of prozone effect, and complement-fixation was determined using C1q, C4d, or C3d assays.

RESULTS:

Among DSA+ study patients, 44 recipients (51%) had AMR, 24 of them showing C4d-positive rejection. Although DSA number or HLA class specificity were not different, patients with AMR or C4d + AMR showed significantly higher IgG, C1q, and C3d DSA MFI than nonrejecting or C4d-negative patients, respectively. Overall, the predictive value of DSA characteristics was moderate, whereby the highest accuracy was computed for peak IgG MFI (AMR, 0.73; C4d + AMR, 0.71). Combined analysis of antibody characteristics in multivariate models did not improve AMR prediction.

CONCLUSIONS:

We estimate a 50% prevalence of silent AMR in DSA+ long-term recipients and conclude that assessment of IgG MFI may add predictive accuracy, without an independent diagnostic advantage of detecting complement-fixation.

PMID:
27120452
DOI:
10.1097/TP.0000000000001195
[Indexed for MEDLINE]

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