Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment
Tyrberg, Linnéa LU
; Andersson, Fanny
; Uhlin, Fredrik
LU
; Hellmark, Thomas
LU
and Segelmark, Mårten
LU
(2024)
In Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
39(1).
p.45-54
- Abstract
BACKGROUND: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination is not determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and IgG subclass distribution. By utilizing samples from the GOOD-IDES-01 trial, where imlifidase, cleaving all IgG in vivo within hours, was given to 15 anti-GBM patients, we aimed to address this by characterizing the autoantibody profile in anti-GBM patients.
METHODS: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope... (More)
BACKGROUND: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination is not determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and IgG subclass distribution. By utilizing samples from the GOOD-IDES-01 trial, where imlifidase, cleaving all IgG in vivo within hours, was given to 15 anti-GBM patients, we aimed to address this by characterizing the autoantibody profile in anti-GBM patients.
METHODS: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data.
RESULTS: Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73m2, p = 0.055), and patients with dialysis at 6 months had a higher EB/EA ratio at rebound (0.8 vs 0.5, p = 0.047). Moreover, 2 patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients, only 1 patient remained ANCA positive at 6 months.
CONCLUSIONS: In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. ANCA was in this study removed early and long-term by imlifidase and cyclophosphamide.
(Less)
- author
- Tyrberg, Linnéa
LU
; Andersson, Fanny
; Uhlin, Fredrik
LU
; Hellmark, Thomas
LU
and Segelmark, Mårten
LU
- organization
- publishing date
- 2024
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
- volume
- 39
- issue
- 1
- pages
- 45 - 54
- publisher
- Oxford University Press
- external identifiers
-
- scopus:85180568690
- pmid:37385828
- ISSN
- 1460-2385
- DOI
- 10.1093/ndt/gfad132
- project
- Formation and Removal of Autoantibodies in Rapidly Progressive Glomerulonephritis
- language
- English
- LU publication?
- yes
- additional info
- © The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.
- id
- f5752182-7a5c-45ae-9f1f-02313400713d
- date added to LUP
- 2023-10-09 13:12:00
- date last changed
- 2024-04-22 21:03:30
@article{f5752182-7a5c-45ae-9f1f-02313400713d,
abstract = {{<p>BACKGROUND: Autoantibodies are common in glomerulonephritis, but the clinical benefit of rapid elimination is not determined, even in anti-glomerular basement membrane (GBM) disease. Even less is known about the importance of autoantibody characteristics, including epitope specificity and IgG subclass distribution. By utilizing samples from the GOOD-IDES-01 trial, where imlifidase, cleaving all IgG in vivo within hours, was given to 15 anti-GBM patients, we aimed to address this by characterizing the autoantibody profile in anti-GBM patients.</p><p>METHODS: In the GOOD-IDES-01 trial, plasmapheresis was (re)started if anti-GBM antibodies rebounded. Serum samples were collected prospectively for 6 months and analyzed for anti-GBM epitope specificity using recombinant constructs of the EA and EB epitopes, IgG subclass using monoclonal antibodies, and anti-neutrophil cytoplasmic antibodies (ANCA). The results were correlated with clinical data.</p><p>RESULTS: Patients with a rebound (n = 10) tended to have lower eGFR at 6 months (11 vs 34 mL/min/1.73m2, p = 0.055), and patients with dialysis at 6 months had a higher EB/EA ratio at rebound (0.8 vs 0.5, p = 0.047). Moreover, 2 patients demonstrated increasing epitope restriction and several patients displayed a shift in subclass distribution at rebound. Six patients were double positive for ANCA. ANCA rebound was seen in 50% of patients, only 1 patient remained ANCA positive at 6 months.</p><p>CONCLUSIONS: In this study, rebound of anti-GBM antibodies, especially if directed against the EB epitope, was associated with a worse outcome. This supports the notion that all means should be used to eliminate anti-GBM antibodies. ANCA was in this study removed early and long-term by imlifidase and cyclophosphamide.</p>}},
author = {{Tyrberg, Linnéa and Andersson, Fanny and Uhlin, Fredrik and Hellmark, Thomas and Segelmark, Mårten}},
issn = {{1460-2385}},
language = {{eng}},
number = {{1}},
pages = {{45--54}},
publisher = {{Oxford University Press}},
series = {{Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}},
title = {{Using imlifidase to elucidate the characteristics and importance of anti-GBM antibodies produced after start of treatment}},
url = {{http://dx.doi.org/10.1093/ndt/gfad132}},
doi = {{10.1093/ndt/gfad132}},
volume = {{39}},
year = {{2024}},
}