Quantitative and Longitudinal Assessment of Systemic Innate Immunity in Health and Disease Using a 2D Gene Model

Area of Science:

• Immunology
• Genomics
• Infectious Diseases

Background:

• Innate immunity dysregulation is central to infectious and autoimmune diseases.
• Convenient monitoring of systemic innate immunity is crucial for understanding pathogenesis and improving disease management.
• Previous work focused on host transcriptional responses to infection in peripheral blood.

Purpose of the Study:

• To develop and validate a 2D gene model for simultaneous assessment of systemic innate immunity.
• To evaluate the model's utility in distinguishing viral and bacterial infection signatures.
• To explore the clinical applications of this model in various health and disease states.

Main Methods:

• Development of a 2D gene model incorporating VirSig (viral response) and BacSig (bacterial response).
• Application of the model to diverse transcriptome datasets from healthy individuals and patients with various conditions.
• Analysis of signature patterns in acute infections, pregnancy, tuberculosis, cystic fibrosis, SSc-ILD, and SLE.

Main Results:

• Distinct VirSig and BacSig patterns identified in viral and bacterial infections, respectively.
• Healthy adults showed restricted signature ranges, with notable elevations during pregnancy and development.
• Abnormal signatures observed in active TB, CF, SSc-ILD, and SLE, with associations to disease severity and treatment response.

Conclusions:

• The 2D gene model effectively assesses systemic innate immunity in health and disease.
• Potential clinical applications include patient stratification, antibiotic prescription guidance, pathogenesis insights, and treatment monitoring.
• This model offers a novel tool for understanding and managing immune-related conditions.