eprintid: 10198676
rev_number: 12
eprint_status: archive
userid: 699
dir: disk0/10/19/86/76
datestamp: 2024-10-21 10:30:43
lastmod: 2025-03-27 12:25:15
status_changed: 2024-10-21 10:30:43
type: article
metadata_visibility: show
sword_depositor: 699
creators_name: Chong, Stephanie MY
creators_name: Hung, Rachel KY
creators_name: Chang, Fernando Yuen
creators_name: Atkinson, Claire
creators_name: Fernando, Raymond
creators_name: Harber, Mark
creators_name: Magee, Ciara N
creators_name: Salama, Alan D
creators_name: Reeves, Matthew
title: Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D15
keywords: Post-transplant infections; BK virus; Kidney transplantation; BKV serotyping
note: Copyright © 2024 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC license
(http://creativecommons.org/licenses/by-nc/4.0/).
abstract: Background:
BK polyomavirus (BKV) DNAaemia occurs in 10% of recipients of kidney transplants, contributing to premature allograft failure. Evidence suggests disease is donor derived. Hypothetically, recipient infection with a different BKV serotype increases risk due to poorer immunological control. Thus, understanding the composition and activity of the humoral anti-BKV responses in donor/recipient (D/R) pairs is critical.
//
Methods:
Using 224 paired pre-transplant D/R samples, BKV VP1 genotype-specific pseudoviruses were employed to define the breadth of the antibody response against different serotypes (ELISA) and, to characterise specific neutralising activity (nAb) using the 50% inhibitory concentration (LogIC50). Mismatch (MM) ratios were calculated using the ratio of recipient ELISA or nAb reactive BKV serotypes relative to the number of donor reactive serotypes.
//
Findings:
BKV DNAaemia was observed in 28/224 recipients of kidney transplants. These recipients had lower nAb titres against all the serotypes, with median logIC50 values of 1.19–2.91, compared to non-viraemic recipients’ median logIC50 values of 2.13–3.30. nAb D/R MM ratios >0.67 associated with significantly higher risk of BKV viraemia, with an adjusted odds ratio of 5.12 (95% CI 2.07 to 13.04; p < 0.001). Notably, a mismatch against donor serotype Ic and II associated with adjusted odds ratios of 8.12 (95% CI 2.10 to 35.61; p = 0.002) and 4.52 (95% CI 1.19 to 19.23; p = 0.03) respectively. 21 recipients demonstrated broadly neutralising responses against all the serotypes, none of whom developed BKV DNAaemia post-transplant. In contrast, there was poor concordance with PsV-specific ELISA data that quantified the total antibody response against different serotypes.
//
Interpretation:
BKV nAb mismatch predicts post-transplant BKV DNAaemia. Specific mismatches in nAb, rather than total seroreactivity, are key indicators of BKV risk post-transplant. This has the potential to risk-stratify individuals and improve clinical outcomes by influencing the frequency of monitoring and individualised tailoring of immunosuppression. Furthermore, detailed examination of individuals with broadly neutralising responses may provide future therapeutic strategies.
//
Funding:
The research was funded by St. Peters Trust, Royal Free Hospital Charity and Wellcome Trust (grant numbers RFCG1718/05, SPT97 and 204870/Z/WT_/Wellcome Trust/United Kingdom).
date: 2024-12
date_type: published
publisher: Elsevier
official_url: https://doi.org/10.1016/j.ebiom.2024.105430
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 2328665
doi: 10.1016/j.ebiom.2024.105430
lyricists_name: Reeves, Matthew
lyricists_id: MREEV93
actors_name: Reeves, Matthew
actors_id: MREEV93
actors_role: owner
funding_acknowledgements: 204870/Z/WT [Wellcome Trust]; RFCG1718/05 [Royal Free Charity]; SPT97 [St Peter’s Trust for Kidney Bladder & Prostate Research]
full_text_status: public
publication: eBioMedicine
volume: 110
article_number: 105430
issn: 2352-3964
citation:        Chong, Stephanie MY;    Hung, Rachel KY;    Chang, Fernando Yuen;    Atkinson, Claire;    Fernando, Raymond;    Harber, Mark;    Magee, Ciara N;         ... Reeves, Matthew; + view all <#>        Chong, Stephanie MY;  Hung, Rachel KY;  Chang, Fernando Yuen;  Atkinson, Claire;  Fernando, Raymond;  Harber, Mark;  Magee, Ciara N;  Salama, Alan D;  Reeves, Matthew;   - view fewer <#>    (2024)    Composition of the neutralising antibody response predicts risk of BK virus DNAaemia in recipients of kidney transplants.                   eBioMedicine , 110     , Article 105430.  10.1016/j.ebiom.2024.105430 <https://doi.org/10.1016/j.ebiom.2024.105430>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10198676/1/Harber_1-s2.0-S2352396424004663-main.pdf