Clinical Significance of Immune Deposits and Complement System Activation in Patients with FSGS: Findings from the CureGN Study
Bibliographic record
Abstract
Background: Glomerular IgM and C3 deposits are commonly found in FSGS and assumed to be the result of passive trapping rather than immune mechanisms. The clinical significance of IgM and C3 immunostaining, and their association with complement system activation have not been elucidated yet. We sought to assess the value of immunofluorescence (IF) findings and urinary complement fragments in defining disease activity and progression. Methods: FSGS patients with available pathology assessment from the CureGN cohort were reviewed and we tested associations of glomerular Igs and C3 staining intensity by IF with the urinary membrane attack complex (sC5b9), proteinuria and time to a composite outcome, defined by kidney failure or 40% eGFR decline. We compared urinary levels of sC5b9 expressed as creatinine and protein ratios. Results: We analyzed 175 FSGS patients, including 63(36%) incident subjects enrolled within 6 months of pathology review.Glomerular IgM, C3 and IgG deposits were found in 88(50%), 48(27.4%) and 27(15.4%) patients, respectively. 44(91%) and 20(48%) of patients with C3 deposition presented with accompanying IgM and IgG deposition, respectively. C3 deposition was correlated with global sclerosis (r=0.27,p<0.001), interstitial fibrosis and tubular atrophy (IFTA) (r=0.17,p=0.028). In incident patients, urinary sC5b9 levels correlated with total segmental sclerosis (r=0.35,p=0.006) and IFTA (r=0.35,p=0.007). There was no correlation between urinary sC5b9 and the intensity of C3, IgM and IgG staining. IFTA and urinary sC5b9 level at enrollment were independent risk factors for composite outcome (HR 1.92, 95%CI 1.45-2.53,p<0.001 and HR 2.15, 95%CI 1.39-3.33,p<0.001, respectively).(Fig. 1) Conclusion: In patients with FSGS, a higher urinary level of sC5b9 appears to be associated with eGFR loss independently of proteinuria level. Glomerular C3 deposition was associated with fibrotic lesions which was a predictor of disease progression.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 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 source (direct Gemma or distilled Codex), 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".