Elevated Plasma Complement Factors in CRB1-Associated Inherited Retinal Dystrophies.
Lude Moekotte1, Joke H de Boer1, Sanne Hiddingh1
1Department of Ophthalmology, University Medical Center Utrecht, Utrecht, the Netherlands.
Investigative Ophthalmology & Visual Science
|February 21, 2025
Summary
Inflammation and complement factors are altered in CRB1-associated inherited retinal dystrophies (CRB1-IRDs). Genetic links between CRB1 and CFH genes suggest their variants influence disease.
Area of Science:
- Ophthalmology
- Immunology
- Genetics
Background:
- Inherited retinal dystrophies (IRDs) encompass a group of genetic disorders affecting vision.
- CRB1-associated IRDs (CRB1-IRDs) are a subset of these conditions with specific genetic underpinnings.
- Understanding the molecular mechanisms, including immune responses, is crucial for CRB1-IRDs.
Purpose of the Study:
- To profile inflammation-related proteins in CRB1-IRDs.
- To investigate complement system factors in CRB1-IRDs.
- To identify immune pathways implicated in CRB1-IRDs.
Main Methods:
- Targeted proteomics using the Olink Explore 384 Inflammation II panel.
- Analysis of plasma samples from CRB1-IRD patients and controls.
- Genotyping of patients and controls across two cohorts.
Main Results:
- Significant enrichment of complement cascade factors in CRB1-IRD plasma proteomes.
- Elevated plasma levels of complement factor I and complement factor H (CFH).
- Linkage disequilibrium between CRB1 variants and a common CFH variant (rs7535263), associated with altered CFH-related protein levels.
Conclusions:
- CRB1-IRDs exhibit altered plasma levels of complement factors and innate immune proteins.
- Genetic linkage between CRB1 and CFH genes suggests a role for CFH-CFHR locus variants.
- Functional variants in the CFH-CFHR locus may interact with specific pathogenic CRB1 variants in CRB1-IRDs.
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