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Complement Activating HLA Class 2 Antibodies Are Associated with Poor Renal Allograft Survival; Multicentre Study

A. Babu,1,2 O. Shaw,5 N. Khovanova,2 S. Griffin,4 D. Briggs,6 N. Krishnan,1 S. Fletcher,1 C. Imray,1 A. Seitz,3 R. Baker,3 M. Wellberry-Smith,3 B. Clarke,3 K. Cullen,3 F. Edwards,4 T. Rees,4 E. Burrows,4 L. Howe,5 R. Vaughan,5 N. Kessaris,7 N. Mamode,7 A. Dorling,7 D. Zehnder,1 R. Higgins,1,2 D. Mitchell,2 S. Daga.2,3

1Renal Transplantation, University Hospitals Coventry, Coventry, United Kingdom
2University of Warwick, Coventry, United Kingdom
3Renal Transplantation, St James University Hospital, Leeds, United Kingdom
4Renal Transplantation, University Hospital of Wales, Cardiff, United Kingdom
5H&I, Viapath,, London, United Kingdom
6H&I, NHSBT, Birmingham, United Kingdom
7Renal Transplantation, Guys and St Thomas Hospital, London, United Kingdom.

Meeting: 2018 American Transplant Congress

Abstract number: D113

Keywords: Antibodies, Graft survival, Highly-sensitized, HLA antigens

Session Information

Session Name: Poster Session D: Kidney Complications: Late Graft Failure

Session Type: Poster Session

Date: Tuesday, June 5, 2018

Session Time: 6:00pm-7:00pm

 Presentation Time: 6:00pm-7:00pm

Location: Hall 4EF

Introduction

Role of Class I and II pre-formed complement activating antibodies on renal outcomes is not well defined. In this multicentre study, we looked at the difference in renal allograft outcomes in the presence of HLA class I and II antibodies and their complement activating properties.

Methods

169 highly sensitized patients' samples from four transplant centers were analysed. Following Inclusion criteria were met: presence of DSA (MFI >1000) before desensitization; The exclusion criteria were: dual HLA and ABO incompatible transplants; age<18 years; patients lost to follow up; primary non-function of the graft.

Results

Of 169 patients, 127 patients had HLA class 1 DSA and 108 had HLA class II. 60 patients had C3d positive DSA. 21 patients had HLA class I C3d DSA and 41 patients had HLA class II. Post-transplant median follow-up was 41 months (IQR 13 – 74). 42 grafts failed. 34 patients had class I DSA of which only 7 were C3d positive; 29 patients had HLA class II DSA of which 17 were C3d positive. In Kaplan Meier survival analysis neither class I or II IgG DSA was associated with graft failure (log rank p 0.43 and log-rank p 0.35 respectively). HLA Class II C3d DSA was associated with graft failure (log rank p 0.012) but not HLA class I C3d DSA (log rank p 0.57).

Discussion

In this multicentre study of highly sensitized patients,pre-formed HLA class 2 complement activating donor-specific antibodies is associated with poor renal allograft survival. Will verify this finding in a multivariate analysis. Underlying mechanisms to explain the differences will be studied as well.

CITATION INFORMATION: Babu A., Shaw O., Khovanova N., Griffin S., Briggs D., Krishnan N., Fletcher S., Imray C., Seitz A., Baker R., Wellberry-Smith M., Clarke B., Cullen K., Edwards F., Rees T., Burrows E., Howe L., Vaughan R., Kessaris N., Mamode N., Dorling A., Zehnder D., Higgins R., Mitchell D., Daga S. Complement Activating HLA Class 2 Antibodies Are Associated with Poor Renal Allograft Survival; Multicentre Study Am J Transplant. 2017;17 (suppl 3).

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To cite this abstract in AMA style:

Babu A, Shaw O, Khovanova N, Griffin S, Briggs D, Krishnan N, Fletcher S, Imray C, Seitz A, Baker R, Wellberry-Smith M, Clarke B, Cullen K, Edwards F, Rees T, Burrows E, Howe L, Vaughan R, Kessaris N, Mamode N, Dorling A, Zehnder D, Higgins R, Mitchell D, Daga S. Complement Activating HLA Class 2 Antibodies Are Associated with Poor Renal Allograft Survival; Multicentre Study [abstract]. https://atcmeetingabstracts.com/abstract/complement-activating-hla-class-2-antibodies-are-associated-with-poor-renal-allograft-survival-multicentre-study/. Accessed May 16, 2025.

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