Immunological risk identified by single-cell multi-omics and cardiovascular outcomes

Area of Science:

• Immunology
• Cardiovascular Medicine
• Genomics

Background:

• Atherosclerosis development is influenced by inflammation and autoimmunity.
• Established inflammatory markers like hsCRP and IL-6 incompletely define cardiovascular risk.
• Novel immunological determinants of cardiovascular risk require identification.

Purpose of the Study:

• To detect immunological signals associated with increased cardiovascular risk.
• To explore immune cell signatures beyond conventional inflammatory markers.
• To identify novel biomarkers for coronary artery disease (CAD) and cardiovascular mortality.

Main Methods:

• A nested case-control study within the LURIC cohort (n=3316).
• Comprehensive immunophenotyping of 44 individuals using bulk RNA, scRNA, TCR sequencing, mass cytometry, and cytokine analysis.
• Multi-omics factor analysis to identify shared transcriptional programs, validated in independent cohorts.

Main Results:

• Identified prominent T-cell signatures of proliferation, activation, memory, clonal expansion, and interferon signaling.
• Discovered immune cell types and transcriptional programs linked to CAD status and poor survival, independent of hsCRP and IL-6.
• Replicated findings across multiple cohorts and confirmed cellular proliferation in atherosclerotic plaques.

Conclusions:

• Multi-omic profiling of immune cells reveals novel immune signatures associated with CAD and cardiovascular outcomes.
• These signatures are independent of systemic inflammation and may serve as future risk stratification tools.
• The study provides a proof-of-concept for using detailed immune profiling in cardiovascular risk assessment.