The Mediating Effect of Inflammatory Biomarkers in the Associations Between Sarcoidosis and Incident Ischemic Stroke: A Prospective Cohort Study.

Sarcoidosis was found to independently increase the risk of ischemic stroke in a large prospective cohort.

• HR = 1.335 (95% CI: 1.002–1.779) from multivariable Cox regression analysis
• The cohort included 452,382 UK Biobank participants followed for an average of 13.8 years
• Sarcoidosis cases numbered n = 1,760
• Sensitivity analysis using propensity score matching yielded consistent effect estimates (HR = 1.37)
• Authors describe this as 'the first evidence of a significant association between sarcoidosis and ischemic stroke in a large cohort'

Three inflammatory biomarkers were identified as significant mediators in the association between sarcoidosis and ischemic stroke.

• The systemic immune-inflammation index (SII) mediated 8.43% of the association
• Lymphocyte percentage mediated 7.38% of the association
• C-reactive protein (CRP) mediated 2.17% of the association
• Mediation analysis was used to evaluate the role of each inflammatory marker

Transcriptomic analysis identified three genes differentially expressed in both sarcoidosis and ischemic stroke.

• The three overlapping genes identified were ANKRD22, FCGR1A, and NOG
• Transcriptomic profiles were sourced from the GEO database, specifically datasets GSE58294 and GSE19314
• Differential gene expression, GO and KEGG pathway enrichment, and protein-protein interaction network analyses were performed
• The TGF-β/BMP signaling pathway and immune regulatory network were highlighted as shared molecular underpinnings

The study integrated multi-omics approaches combining large-scale epidemiological data with transcriptomic profiling to explore shared molecular frameworks between sarcoidosis and ischemic stroke.

• UK Biobank data (n = 452,382) were combined with transcriptomic profiles from the GEO database
• Analytical methods included multivariable Cox regression, mediation analysis, differential gene expression, GO and KEGG pathway enrichment, and protein-protein interaction networks
• Sarcoidosis is characterized by granulomatous inflammation across multiple systems
• The study follow-up averaged 13.8 years