Complement activation in anti-glomerular basement membrane disease before and after treatment with imlifidase
Bibliographic record
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 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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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".