IgG2c subclass dominance drives fatal lupus-like nephritis via FcγR and complement activation
Bibliographic record
Abstract
Lupus nephritis (LN) is a leading cause of mortality in systemic lupus erythematosus. While the dominance of Fcγ receptor (FcγR)-activating IgG subclasses has been observed in both human and murine LN, whether this imbalance is causal or merely correlative remains unresolved. To address this, we generated a murine model that exclusively expresses the activating IgG2c while lacking all other IgG subclasses. Despite preserved B cell receptor diversity and intact humoral immunity, these mice developed rapidly progressive and fatal lupus-like nephritis, with 100% mortality by 30 weeks, characterized by extensive renal inflammation. Genetic ablation of FcγRs or complement C3 rescued this phenotype, establishing both as essential and non-redundant mediators of disease. Supporting clinical relevance, renal biopsies from patients with LN exhibited glomerular immune deposits enriched for FcγR-activating IgG1 and minimal inhibitory IgG4. Together, these results identify IgG subclass dominance as a direct driver of LN and provide a fully penetrant, rapid-onset disease model for therapeutic studies.
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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 | 0.000 | 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 | 0.001 | 0.001 |
| 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".