Investigating the Role of the Complement System in Paediatric Sickle Cell Disease
Bibliographic record
Abstract
Background: Sickle cell disease (SCD) is one of the most common hereditary red blood cell (RBC) disorders in the world, with an estimated 300,000 infants born with the disease annually. In SCD, a mutation in the gene for β-globin results in rigid sickled RBCs that can form blockages in the micro-vessels within organs, such as the kidney, leading to RBC lysis, endothelial cell (EC) damage, ischemia/reperfusion injury, and extremely painful vaso-occlusive crises (VOC). SCD can give rise to a variety of renal manifestations such as hyperfiltration, microalbuminuria, and AKI. Approximately 16-18% of overall mortality in patients with SCD is ascribed to kidney disease. The complement system - a critical part of the innate immune system - is involved in a myriad of kidney and vascular disorders, and emerging research points to the involvement of complement in SCD, potentially contributing to sickle cell nephropathy (Fig. 1A). Methods: Paediatric patients with SCD (HbSS or HbS/β0) were enrolled during hospital admission with diagnosed VOC or acute chest crisis (ACS) not caused by infection. Patient serum was collected during hospital admission (crisis) and during follow-up (steady state). Complement activity was measured using the WIESLAB Complement System Screen (Svar Life Science). Immunofluorescence (IF) imaging was used to measure the deposition of C3b and C5b-9 on the surface of ECs exposed to patient serum. Results: There is equal classical and alternative pathway activity during disease steady state and crisis, with an interesting trend showing elevated MBL pathway activity during crisis compared to steady state (Fig. 1B). IF assay data shows significantly elevated deposition of C3b and C5b-9 proteins on ECs when comparing crisis samples and healthy controls, with a trend suggesting a potential difference in complement deposition between steady state and crisis patients (Fig. 1C). Conclusions: Our preliminary data shows complement is active in SCD, resulting in elevated C3b and C5b-9 deposition on ECs during SCD crisis. Future work will focus on further quantifying complement activity, and assessing the functional consequences of this on the surface of ECs. Funding: Commercial Support - Pfizer, Government Support - Non-U.S.
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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 | 0.001 |
| 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 | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".