Association of C1q-fixing DSA with late graft failure in pediatric renal transplant recipients
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We investigated the prognostic value of overall and complement-binding donor-specific HLA antibodies (DSA) in pediatric patients undergoing clinically indicated graft biopsies and their association with graft outcome and specific histological lesions.
Sera of 62 patients at time of indication biopsy ≥1 year posttransplant were assessed for DSA and C1q-fixing DSA by single-antigen bead (SAB) technology.
Twenty-six patients (42 %) were DSA-positive at time of indication biopsy and nine (15 %) were C1q-positive. At 4 years postbiopsy, patients with C1q-positivity had a low graft survival (11 %) compared to DSA-positive, C1q-negative patients (82 %, p = 0.001) and to DSA-negative patients (88 %, p < 0.001). The majority (89 %) of C1q-positive patients were diagnosed with active chronic antibody-mediated rejection (ABMR). C1q DSA-positivity [adjusted hazard ratio (HR) 6.35], presence of transplant glomerulopathy (HR 9.54), and estimated glomerular filtration rate (eGFR) at the time of indication biopsy (HR 0.91) were risk factors for subsequent graft loss.
The presence of C1q-positive DSA in the context of an indication biopsy identifies a subgroup of pediatric renal transplant recipients with a markedly increased risk of subsequent graft loss. Because a fraction of DSA-positive patients escape rejection or graft dysfunction, the C1q assay increases the specificity of a positive DSA result regarding unfavorable transplant outcome.
KeywordsC1q-binding donor-specific antibodies Donor-specific antibodies Pediatrics Renal transplantation Indication biopsy Graft failure
We wish to thank Mirjam Hammer, Fatma Karci, Marzena Kirschke, Birte Leuser, Gabi Gros, Barbara Rüsi-Elsener, Serey-Phorn Sea, and our HLA and DNA laboratory teams for excellent technical assistance.
Compliance with ethical standards
Patient consent and ethics committee approval was obtained, and the investigations were performed in accordance with the Declaration of Helsinki and Good Clinical Practice (GCP) guidelines.
This study was supported by a grant from Novartis Germany.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
- 3.Chaudhuri A, Ozawa M, Everly MJ, Ettenger R, Dharnidharka V, Benfield M, Mathias R, Portale A, McDonald R, Harmon W, Kershaw D, Vehaskari VM, Kamil E, Baluarte HJ, Warady B, Li L, Sigdel TK, Hsieh SC, Dai H, Naesens M, Waskerwitz J, Salvatierra O Jr, Terasaki PI, Sarwal MM (2013) The clinical impact of humoral immunity in pediatric renal transplantation. J Am Soc Nephrol 24:655–664CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Tait BD, Susal C, Gebel HM, Nickerson PW, Zachary AA, Claas FH, Reed EF, Bray RA, Campbell P, Chapman JR, Coates PT, Colvin RB, Cozzi E, Doxiadis II, Fuggle SV, Gill J, Glotz D, Lachmann N, Mohanakumar T, Suciu-Foca N, Sumitran-Holgersson S, Tanabe K, Taylor CJ, Tyan DB, Webster A, Zeevi A, Opelz G (2013) Consensus guidelines on the testing and clinical management issues associated with HLA and nonHLA antibodies in transplantation. Transplantation 95:19–47CrossRefPubMedGoogle Scholar
- 12.Loupy A, Lefaucheur C, Vernerey D, Prugger C, Duong van Huyen JP, Mooney N, Suberbielle C, Fremeaux-Bacchi V, Mejean A, Desgrandchamps F, Anglicheau D, Nochy D, Charron D, Empana JP, Delahousse M, Legendre C, Glotz D, Hill GS, Zeevi A, Jouven X (2013) Complement-binding anti-HLA antibodies and kidney-allograft survival. N Engl J Med 369:1215–1226CrossRefPubMedGoogle Scholar
- 13.Susal C, Wettstein D, Dohler B, Morath C, Ruhenstroth A, Scherer S, Tran TH, Gombos P, Schemmer P, Wagner E, Fehr T, Zivcic-Cosic S, Balen S, Weimer R, Slavcev A, Bosmuller C, Norman DJ, Zeier M, Opelz G, Report ACTS (2015) Association of kidney graft loss with De novo produced donor-specific and Non-donor-specific HLA antibodies detected by single antigen testing. Transplantation 99:1976–1980CrossRefPubMedGoogle Scholar
- 15.Guidicelli G, Guerville F, Lepreux S, Wiebe C, Thaunat O, Dubois V, Visentin J, Bachelet T, Morelon E, Nickerson P, Merville P, Taupin JL, Couzi L (2015) Non-complement-binding De novo donor-specific anti-HLA antibodies and kidney allograft survival. J Am Soc Nephrol. doi: 10.1681/ASN.2014040326 PubMedGoogle Scholar
- 18.Freitas MC, Rebellato LM, Ozawa M, Nguyen A, Sasaki N, Everly M, Briley KP, Haisch CE, Bolin P, Parker K, Kendrick WT, Kendrick SA, Harland RC, Terasaki PI (2013) The role of immunoglobulin-G subclasses and C1q in de novo HLA-DQ donor-specific antibody kidney transplantation outcomes. Transplantation 95:1113–1119CrossRefPubMedGoogle Scholar
- 22.Sis B, Mengel M, Haas M, Colvin RB, Halloran PF, Racusen LC, Solez K, Baldwin WM 3rd, Bracamonte ER, Broecker V, Cosio F, Demetris AJ, Drachenberg C, Einecke G, Gloor J, Glotz D, Kraus E, Legendre C, Liapis H, Mannon RB, Nankivell BJ, Nickeleit V, Papadimitriou JC, Randhawa P, Regele H, Renaudin K, Rodriguez ER, Seron D, Seshan S, Suthanthiran M, Wasowska BA, Zachary A, Zeevi A (2010) Banff '09 meeting report: antibody mediated graft deterioration and implementation of Banff working groups. Am J Transplant 10:464–471CrossRefPubMedGoogle Scholar
- 23.Ginevri F, Nocera A, Comoli P, Innocente A, Cioni M, Parodi A, Fontana I, Magnasco A, Nocco A, Tagliamacco A, Sementa A, Ceriolo P, Ghio L, Zecca M, Cardillo M, Garibotto G, Ghiggeri GM, Poli F (2012) Posttransplant de novo donor-specific hla antibodies identify pediatric kidney recipients at risk for late antibody-mediated rejection. Am J Transplant 12:3355–3362CrossRefPubMedGoogle Scholar