Common Toll-like receptor 7 variants define disease risk and phenotypes in juvenile-onset systemic lupus erythematosus
1Immunology Department Laboratory, Referral Medical Biology Laboratory, Institut Fédératif de Biologie, Toulouse University Hospital Center, France; INFINITy, Toulouse Institute for Infectious and Inflammatory Diseases, INSERM, U1291, CNRS U5051, University Toulouse III, Toulouse, France.
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Summary
Genetic variations in Toll-like receptor 7 (TLR7) influence juvenile systemic lupus erythematosus (jSLE) risk and disease presentation. These TLR7 gene variants show ancestry-specific effects, impacting disease activity and organ involvement in jSLE patients.
Area of Science:
- Immunogenetics
- Rheumatology
- Molecular Biology
Background:
- Toll-like receptor 7 (TLR7) plays a role in type I interferon (IFN) expression, a key factor in systemic lupus erythematosus (SLE).
- Investigating genetic variability in TLR7 is crucial for understanding the pathogenesis of juvenile-onset SLE (jSLE).
Purpose of the Study:
- To investigate the genetic variability of TLR7 in a UK cohort of 319 juvenile-onset SLE (jSLE) patients.
- To associate common TLR7 variants with demographic and clinical features of jSLE.
- To explore the functional impact of identified TLR7 variants on gene expression and disease risk.
Main Methods:
- Next-generation sequencing was employed to identify common TLR7 variants in jSLE patients.
- In silico analysis was used to predict the functional impact of identified variants.
- Statistical analyses (Odds Ratios, 95% Confidence Intervals) were performed to associate variants with clinical features and ancestry.
Main Results:
- Three common TLR7 variants (rs2302267, rs179008, rs3853839) with predicted functional impact were identified.
- The TLR7 variant rs3853839 showed increased jSLE risk in African/Caribbean girls but reduced risk in European girls.
- Specific TLR7 variants were associated with mucocutaneous activity, age at diagnosis, C3 consumption, anti-dsDNA levels, and global disease activity, with ancestry-specific correlations.
Conclusions:
- Common TLR7 variants can influence the risk and organ involvement in jSLE in an ancestry-specific manner.
- The identified variants, rs2302267 and rs3853839, may affect TLR7 promoter activity and mRNA stability, respectively.
- These findings support genetic risk stratification and suggest considering TLR7 gene variants for personalized jSLE treatment strategies.