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Complement activation in anti-glomerular basement membrane disease before and after treatment with imlifidase

Tyrberg, Linnéa LU orcid ; Uhlin, Fredrik LU ; Alam, Shanavaz ; Sonesson, Elisabeth ; Hellmark, Thomas LU orcid ; Blom, Anna M LU orcid and Segelmark, Mårten LU orcid (2026) In Clinical Kidney Journal 19(1).
Abstract

BACKGROUND: The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease.

METHODS: The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal... (More)

BACKGROUND: The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease.

METHODS: The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal complement complexes (sTCC)]. Ratios of C4d/C4 and C3bBbP/C3 were calculated to correct for plasmapheresis. Serum samples were analyzed for anti-drug antibodies (ADA) directed against imlifidase.

RESULTS: The C4d/C4 ratio decreased rapidly from its pre-dose level, while sTCC decreased more slowly. sTCC and C3bBbP/C3 were above the reference level throughout the trial. We observed a transient increase in C4d/C4 and C3bBbP/C3, but not sTCC, immediately following treatment with imlifidase, which tended to be more pronounced in patients with more pre-existing ADA.

CONCLUSIONS: Classical pathway activation decreased rapidly after autoantibody removal by imlifidase and increased again in most of those that experienced a rebound, but terminal complement activation remained elevated throughout the trial. However, due to the small sample size our results must be interpreted with caution.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Kidney Journal
volume
19
issue
1
article number
faf393
publisher
Oxford University Press
external identifiers
  • pmid:41522684
ISSN
2048-8505
DOI
10.1093/ckj/sfaf393
language
English
LU publication?
yes
additional info
© The Author(s) 2025. Published by Oxford University Press on behalf of the ERA.
id
c372975e-8ed4-45ce-822c-26f15ea7d5ac
date added to LUP
2026-01-20 12:54:54
date last changed
2026-01-20 16:29:25
@article{c372975e-8ed4-45ce-822c-26f15ea7d5ac,
  abstract     = {{<p>BACKGROUND: The involvement of the complement system in anti-glomerular basement membrane (GBM) disease is well known but incompletely characterized. The ability of autoantibodies to trigger the classical pathway is evident, while the lectin and alternative pathways also seem to be of importance. We studied complement activation in patients treated with imlifidase, which leads to rapid IgG depletion, to elucidate the role of complement in anti-GBM disease.</p><p>METHODS: The GOOD-IDES-01 trial included 15 anti-GBM disease patients treated with one dose of imlifidase in addition to standard therapy with 6 months of follow-up. Plasma samples were analyzed for C3, C4 and complement activation products [C4d, C3bBbP and soluble terminal complement complexes (sTCC)]. Ratios of C4d/C4 and C3bBbP/C3 were calculated to correct for plasmapheresis. Serum samples were analyzed for anti-drug antibodies (ADA) directed against imlifidase.</p><p>RESULTS: The C4d/C4 ratio decreased rapidly from its pre-dose level, while sTCC decreased more slowly. sTCC and C3bBbP/C3 were above the reference level throughout the trial. We observed a transient increase in C4d/C4 and C3bBbP/C3, but not sTCC, immediately following treatment with imlifidase, which tended to be more pronounced in patients with more pre-existing ADA.</p><p>CONCLUSIONS: Classical pathway activation decreased rapidly after autoantibody removal by imlifidase and increased again in most of those that experienced a rebound, but terminal complement activation remained elevated throughout the trial. However, due to the small sample size our results must be interpreted with caution.</p>}},
  author       = {{Tyrberg, Linnéa and Uhlin, Fredrik and Alam, Shanavaz and Sonesson, Elisabeth and Hellmark, Thomas and Blom, Anna M and Segelmark, Mårten}},
  issn         = {{2048-8505}},
  language     = {{eng}},
  number       = {{1}},
  publisher    = {{Oxford University Press}},
  series       = {{Clinical Kidney Journal}},
  title        = {{Complement activation in anti-glomerular basement membrane disease before and after treatment with imlifidase}},
  url          = {{http://dx.doi.org/10.1093/ckj/sfaf393}},
  doi          = {{10.1093/ckj/sfaf393}},
  volume       = {{19}},
  year         = {{2026}},
}