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Pediatric Nephrology

, Volume 31, Issue 7, pp 1157–1166 | Cite as

Association of C1q-fixing DSA with late graft failure in pediatric renal transplant recipients

  • Alexander Fichtner
  • Caner Süsal
  • Britta Höcker
  • Susi Rieger
  • Rüdiger Waldherr
  • Jens H Westhoff
  • Anja Sander
  • Gerhard Opelz
  • Burkhard Tönshoff
Original Article

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

C1q-binding donor-specific antibodies Donor-specific antibodies Pediatrics Renal transplantation Indication biopsy Graft failure 

Notes

Acknowledgements

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.

Funding

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.

Supplementary material

467_2016_3322_MOESM1_ESM.doc (42 kb)
ESM 1 (DOC 42 kb)
467_2016_3322_MOESM2_ESM.tif (73 kb)
ESM 2 (TIF 72 kb)
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High-resolution image (GIF 93 kb)

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Copyright information

© IPNA 2016

Authors and Affiliations

  • Alexander Fichtner
    • 1
  • Caner Süsal
    • 2
  • Britta Höcker
    • 1
  • Susi Rieger
    • 1
  • Rüdiger Waldherr
    • 3
  • Jens H Westhoff
    • 1
  • Anja Sander
    • 4
  • Gerhard Opelz
    • 2
  • Burkhard Tönshoff
    • 1
  1. 1.Department of Pediatrics IUniversity Children’s Hospital HeidelbergHeidelbergGermany
  2. 2.Department of Transplantation Immunology, Institute of ImmunologyUniversity of HeidelbergHeidelbergGermany
  3. 3.Institute of Clinical Pathology HeidelbergHeidelbergGermany
  4. 4.Institute of Medical Biometry and InformaticsUniversity of HeidelbergHeidelbergGermany

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