Antibody-mediated rejection despite inhibition of terminal complement

Andrew Bentall, Dolly B. Tyan, Flavia Sequeira, Matthew J. Everly, Manish J. Gandhi, Lynn D. Cornell, Han Li, Nicole A. Henderson, Suresh Raghavaiah, Jeffrey L. Winters, Patrick G. Dean, Mark D Stegall

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33 Citations (Scopus)

Abstract

Terminal complement blockade has been shown to decrease the incidence of early acute antibody-mediated rejection (eAMR) in the first month after positive cross-match kidney transplant recipients, yet some patients still develop eAMR. The current study investigated possible mechanisms of eAMR despite eculizumab treatment. Of the 26 patients treated with eculizumab, two developed clinical eAMR and another patient developed histologic signs of eAMR without graft dysfunction ('subclinical eAMR'). Twenty-three did not have histologic injury on early surveillance biopsies. All 26 patients had therapeutic levels of eculizumab and showed complete blockade of complement in hemolytic assays. High levels of donor-specific alloantibody (DSA) including total IgG, IgG3, and C1q+ DSA were present in patients with and without eAMR, and none correlated well with eAMR. In contrast, IgM DSA was present in only four patients after transplantation: the two patients with clinical eAMR, one patient with subclinical AMR, and one patient without eAMR (P = 0.006 correlation with eAMR). Both clinical eAMR episodes were easily treated with plasma exchange which removed IgM more completely and rapidly than IgG, resulting in normalization of function and histology. These data suggest a possible role of antidonor IgM DSA in the pathogenesis of eAMR in patients treated with terminal complement blockade (ClinicalTrials.gov Identifier: NCT00670774).

Original languageEnglish (US)
Pages (from-to)1235-1243
Number of pages9
JournalTransplant International
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2014

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Antibodies
Isoantibodies
Tissue Donors
Immunoglobulin M
Immunoglobulin G
Plasma Exchange
Graft Rejection
Histology
Complement System Proteins
Transplantation
Kidney
Biopsy
Incidence
Wounds and Injuries
Therapeutics
eculizumab

Keywords

  • anti-HLA antibodies
  • antibody-mediated rejection
  • complement
  • IgM
  • kidney transplantation
  • sensitized recipients

ASJC Scopus subject areas

  • Transplantation

Cite this

Bentall, A., Tyan, D. B., Sequeira, F., Everly, M. J., Gandhi, M. J., Cornell, L. D., ... Stegall, M. D. (2014). Antibody-mediated rejection despite inhibition of terminal complement. Transplant International, 27(12), 1235-1243. https://doi.org/10.1111/tri.12396

Antibody-mediated rejection despite inhibition of terminal complement. / Bentall, Andrew; Tyan, Dolly B.; Sequeira, Flavia; Everly, Matthew J.; Gandhi, Manish J.; Cornell, Lynn D.; Li, Han; Henderson, Nicole A.; Raghavaiah, Suresh; Winters, Jeffrey L.; Dean, Patrick G.; Stegall, Mark D.

In: Transplant International, Vol. 27, No. 12, 01.12.2014, p. 1235-1243.

Research output: Contribution to journalArticle

Bentall, A, Tyan, DB, Sequeira, F, Everly, MJ, Gandhi, MJ, Cornell, LD, Li, H, Henderson, NA, Raghavaiah, S, Winters, JL, Dean, PG & Stegall, MD 2014, 'Antibody-mediated rejection despite inhibition of terminal complement', Transplant International, vol. 27, no. 12, pp. 1235-1243. https://doi.org/10.1111/tri.12396
Bentall A, Tyan DB, Sequeira F, Everly MJ, Gandhi MJ, Cornell LD et al. Antibody-mediated rejection despite inhibition of terminal complement. Transplant International. 2014 Dec 1;27(12):1235-1243. https://doi.org/10.1111/tri.12396
Bentall, Andrew ; Tyan, Dolly B. ; Sequeira, Flavia ; Everly, Matthew J. ; Gandhi, Manish J. ; Cornell, Lynn D. ; Li, Han ; Henderson, Nicole A. ; Raghavaiah, Suresh ; Winters, Jeffrey L. ; Dean, Patrick G. ; Stegall, Mark D. / Antibody-mediated rejection despite inhibition of terminal complement. In: Transplant International. 2014 ; Vol. 27, No. 12. pp. 1235-1243.
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