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

2016; Wolters Kluwer; Volume: 101; Issue: 3 Linguagem: Inglês

10.1097/tp.0000000000001195

1534-6080

Farsad Eskandary, Gregor Bond, Nicolas Kozakowski, Heinz Regele, Lena Marinova, Markus Wahrmann, Željko Kikić, Helmuth Haslacher, Susanne Rasoul‐Rockenschaub, Christopher C. Kaltenecker, Franz König, Luis Hidalgo, Rainer Oberbauer, Philip F. Halloran, Georg A. Böhmig,

Complement system in diseases

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.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.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.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.