Elevated Plasma Complement Factors in <i>CRB1</i> -associated Inherited Retinal Dystrophies
Bibliographic record
Abstract
Abstract Objective To determine the profile of inflammation-related proteins and complement system factors in serum of CRB1 -associated inherited retinal dystrophies ( CRB1 -IRDs). Design A case-control study. Subjects, Participants, and/or Controls A cohort of 30 Dutch CRB1 -IRD patients and 29 Dutch healthy controls (HC) (Cohort I), and a second cohort of 123 CRB1 -IRD patients from 14 countries and 1292 controls (Cohort II) were used in this study. Methods Quantitative 370-plex targeted proteomics in blood plasma and genotyping of the single nucleotide variant (SNV) rs7535263 in the CFH gene. Main Outcome Measures Plasma concentrations of inflammation-related proteins and the genotype of the SNV rs7535263. Results CRB1 -IRD patients showed increased plasma levels of complement system and coagulation cascade proteins compared to healthy controls. Complement Factor I [CFI], Serpin Family D1 [SERPIND1], and Complement Factor H [CFH] were significantly elevated (q<0.05, adjusted for age and sex), which correlated (Pearson’s correlation coefficient >0.6) with higher levels of plasma Complement Component 3 [C3] (q = 0.064). The most enriched pathway in patients was the “Complement cascade” (R-HSA-166658, Padj = P = 3.03 × 10 -15 ). An analysis of the genotype of CFH variant rs7535263, which is in close physical proximity to the CRB1 gene and is associated with other retinal conditions by influencing plasma complement levels, revealed significantly skewed allele distribution specifically in Dutch patients (A allele of rs7535263, odds ratio (OR) [95%CI = 2.85 [1.35-6.02], P = 6.19 × 10 -3 ), but not in a global case-control cohort ( P = 0.12). However, CRB1 missense variants that are common in patients display strong linkage disequilibrium (LD) with rs7535263 in CFH in the UK Biobank (D’ = 0.97 for p.(Cys948Tyr); D’ = 1.0 for p.(Arg764Cys)), indicating that genetic linkage may influence plasma complement factor levels in CRB1 -IRD patients. After accounting for the CFH genotype in the proteomic analyses, we also detected significantly elevated plasma levels of Complement Factor H Related 2 [CFHR2] in CRB1 -IRD patients (q = 0.04). Conclusions CRB1 -IRDs are characterized by changes in plasma levels of complement factors and proteins of the innate immune system, which is influenced by common functional variants in the CFH-CFHR locus. This indicates that innate immunity is implicated in CRB1 -IRDs.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".