Farsad Eskandary1, Gregor Bond, Nicolas Kozakowski, Heinz Regele, Lena Marinova, Markus Wahrmann, Željko Kikić, Helmuth Haslacher, Susanne Rasoul-Rockenschaub, Christopher C Kaltenecker, Franz König, Luis G Hidalgo, Rainer Oberbauer, Philip F Halloran, Georg A Böhmig. 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.
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 C3dDSA 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.
Authors: James H Lan; David Gjertson; Ying Zheng; Stephanie Clark; Elaine F Reed; Michael J Cecka Journal: Am J Transplant Date: 2018-05-09 Impact factor: 8.086
Authors: Jeff Reeve; Georg A Böhmig; Farsad Eskandary; Gunilla Einecke; Carmen Lefaucheur; Alexandre Loupy; Philip F Halloran Journal: JCI Insight Date: 2017-06-15
Authors: Farsad Eskandary; Heinz Regele; Lukas Baumann; Gregor Bond; Nicolas Kozakowski; Markus Wahrmann; Luis G Hidalgo; Helmuth Haslacher; Christopher C Kaltenecker; Marie-Bernadette Aretin; Rainer Oberbauer; Martin Posch; Anton Staudenherz; Ammon Handisurya; Jeff Reeve; Philip F Halloran; Georg A Böhmig Journal: J Am Soc Nephrol Date: 2017-12-14 Impact factor: 10.121
Authors: Elena G Kamburova; Bram W Wisse; Irma Joosten; Wil A Allebes; Arnold van der Meer; Luuk B Hilbrands; Marije C Baas; Eric Spierings; Cornelis E Hack; Franka E van Reekum; Arjan D van Zuilen; Marianne C Verhaar; Michiel L Bots; Adriaan C A D Drop; Loes Plaisier; Marc A J Seelen; Jan Stephan Sanders; Bouke G Hepkema; Annechien J A Lambeck; Laura B Bungener; Caroline Roozendaal; Marcel G J Tilanus; Christina E Voorter; Lotte Wieten; Elly M van Duijnhoven; Mariëlle A C J Gelens; Maarten H L Christiaans; Frans J van Ittersum; Shaikh A Nurmohamed; Neubury M Lardy; Wendy Swelsen; Karlijn A M I van der Pant; Neelke C van der Weerd; Ineke J M Ten Berge; Frederike J Bemelman; Andries J Hoitsma; Paul J M van der Boog; Johan W de Fijter; Michiel G H Betjes; Sebastiaan Heidt; Dave L Roelen; Frans H Claas; Henny G Otten Journal: J Am Soc Nephrol Date: 2018-07-26 Impact factor: 10.121
Authors: Martin Schiemann; Elisabeth Puchhammer-Stöckl; Farsad Eskandary; Philip Kohlbeck; Susanne Rasoul-Rockenschaub; Andreas Heilos; Nicolas Kozakowski; Irene Görzer; Željko Kikić; Harald Herkner; Georg A Böhmig; Gregor Bond Journal: Transplantation Date: 2017-02 Impact factor: 4.939
Authors: José M Arreola-Guerra; Natalia Castelán; Adrián de Santiago; Adriana Arvizu; Norma Gonzalez-Tableros; Mayra López; Isaac Salcedo; Mario Vilatobá; Julio Granados; Luis E Morales-Buenrostro; Josefina Alberú Journal: J Transplant Date: 2016-09-04