Measuring Affinity of Polyclonal HLA-Specific Antibodies in Highly Sensitised Cases Can Serve as an Additional Biomarker to Guide Direct Transplantation

S. Daga,^1,2 D. Lowe,⁶ R. Buchli,³ J. Collard,³ A. Mulder,⁸ C. McMurtrey,^3,4 H. Moyse,⁷ N. Evans,⁷ N. Krishnan,² W. Hildebrand,^3,4 F. Claas,⁸ D. Briggs,⁵ D. Zehnder,^1,2 D. Mithcell,¹ R. Higgins.^1,2

¹Clinical Sciences Research Laboratories, University of Warwick, Coventry, United Kingdom
²Renal Unit, University Hospital, Coventry and Warwickshire NHS Trust, Coventry, United Kingdom
³Pure Protein LLC, Oklahoma
⁴University of Oklahoma Health Science Center, Oklahoma City
⁵Department of Histocompatibility and Immunogenetics, NHS Blood and Transplant, Birmingham, United Kingdom
⁶Department of Histocompatibility and Immunogenetics, Royal Liverpool University Hospital, Liverpool, United Kingdom
⁷School of Engineering, University of Warwick, Coventry, United Kingdom
⁸Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.

Meeting: 2015 American Transplant Congress

Abstract number: B241

Keywords: Highly-sensitized, HLA antibodies, Kidney transplantation

Session Information

Session Name: Poster Session B: Translational Genetics and Proteomics in Transplantation

Session Type: Poster Session

Date: Sunday, May 3, 2015

Session Time: 5:30pm-6:30pm

Presentation Time: 5:30pm-6:30pm

Location: Exhibit Hall E

Significant numbers of patients on transplant waiting lists in the UK are sensitised (43%). Direct transplantation across these HLA-specific antibodies using risk stratification strategies are increasingly being used. However current solid phase assays cannot fully predict graft outcomes following transplantation. We have validated a biosensor platform that allows observation of real time binding of human mAbs and polyclonal IgG on HLA proteins.

Serum samples from 32 highly sensitised cases were processed to enrich IgG and HLA-specificities were confirmed using Luminex single antigen beads. Binding experiments were performed against a range of HLA proteins corresponding to sample anti-HLA specificities.

23/32 patients gave a detectable binding response. In nine cases showing no binding, the highest MFI was below 2500 in 8/9 cases. In 23 positive cases, the binding was observed against 38 HLA specificities studied. The binding kinetics varied between cases. Dissociation constants (KD) ranged between 10-5 to 10-11 M.

This is the first description of affinity measurements in a clinical transplantation cohort using a real-time biosensor platform. The observed dissociation constants had a wide range representing low (10^5 to 10^7 M), moderate (10^7 to 10^9 M) and high (>10^9 M) levels of affinity. HLA-specific antibodies of varying specificity and affinity were present in sera of highly sensitised cases. These data could potentially guide stratification in to three groups based on affinity parameters that may predict risk of antibody-mediated organ damage post-transplantation.

To cite this abstract in AMA style:

Daga S, Lowe D, Buchli R, Collard J, Mulder A, McMurtrey C, Moyse H, Evans N, Krishnan N, Hildebrand W, Claas F, Briggs D, Zehnder D, Mithcell D, Higgins R. Measuring Affinity of Polyclonal HLA-Specific Antibodies in Highly Sensitised Cases Can Serve as an Additional Biomarker to Guide Direct Transplantation [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/measuring-affinity-of-polyclonal-hla-specific-antibodies-in-highly-sensitised-cases-can-serve-as-an-additional-biomarker-to-guide-direct-transplantation/. Accessed December 3, 2024.

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