Unraveling the Lectin Complement Pathway Dynamics in Childhood IgAN
Bibliographic record
Abstract
Background: The lectin complement pathway is pivotal in the pathogenesis of IgA nephropathy (IgAN), yet the precise triggers of its activation remain unknown. Collectin11 (C11), a novel initiator of this pathway, has emerged as a focus of recent research. Concurrently, soluble CD89 (sCD89) has been implicated in kidney inflammation among childhood IgAN (cIgAN) patients. For the first time, this study unveils the intricate interplay between sCD89 and C11 as key drivers of lectin pathway activation, culminating in C5b-9 formation and triggering kidney inflammation. Methods: We conducted a prospective study on one of the largest cIgAN cohorts (n=52), alongside 80 controls. Plasma and urinary C11 and soluble C5b-9 (sC5b-9) levels were quantified via ELISA and correlated with biological, histological, and clinical parameters. Kidney biopsies were analyzed for C5b-9 deposition. Human mesangial cells (HMCs) were assessed for C11 expression and secretion via western blotting, immunofluorescence, and ELISA following stimulation with cIgAN plasma or recombinant sCD89 (rsCD89). HPLC and immunoprecipitation identified C11 in circulating immune complexes (CICs). Results: Elevated sC5b-9 levels correlated with proteinuria severity (r=0.558, p<0.005) and reliably predicted glomerulosclerosis (AUC=0.812, p<0.005), surpassing proteinuria. sC5b-9 levels were linked to glomerular inflammation (p<0.005), crescents (p=0.012), and capillary C5b-9 deposition (p=0.008). Plasma C11 levels were significantly higher in cIgAN patients (p<0.0001), contributing to proteinuria (r=0.520, p<0.005), inflammation (p=0.001), glomerulosclerosis (p=0.006), and crescents (p=0.013). Plasma sC5b-9, C11, sCD89, and IgA-CD89 complex levels showed strong positive correlations, indicating their role in cIgAN. For the first time, we identified C11 in CICs and confirmed its expression and secretion by HMCs. Its upregulation was induced by cIgAN plasma and rsCD89 stimulation, with colocalization alongside C3, supporting lectin pathway activation in cIgAN. Conclusion: Plasma sC5b-9 levels above 250 ng/ml predict severe cIgAN, potentially reducing the need for invasive kidney biopsies. The interplay between C11 and sCD89 provides mechanistic insights into complement pathway activation and offers potential for targeted therapies.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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".