The Contribution of Transcriptomics to Biomarker Development in Systemic Vasculitis and SLE

Area of Science:

• Molecular Biology
• Biomarker Discovery
• Clinical Diagnostics

Background:

• Gene expression biomarkers are emerging for clinical use, particularly in oncology and transplantation.
• Despite potential, many gene expression biomarkers fail to progress beyond initial reports due to development challenges.
• Systematic biases and confounding factors can significantly impact the outcomes of gene expression studies.

Purpose of the Study:

• To review the process of gene expression-based biomarker development, emphasizing validation strategies.
• To examine the application and limitations of gene expression biomarkers in Systemic Lupus Erythematosus (SLE) and systemic vasculitis.
• To discuss the utility of specific gene signatures, including interferon-inducible genes and CD8+ T-cell signatures.

Main Methods:

• Review of gene expression biomarker development processes.
• Analysis of existing literature on gene expression biomarkers in SLE and systemic vasculitis.
• Evaluation of validation methodologies, particularly independent cohort validation.

Main Results:

• Independent cohort validation is essential to mitigate systematic biases in biomarker studies.
• The type 1 interferon-inducible gene signature, while studied in SLE, lacks specificity and has a nuanced association with disease activity.
• Other promising biomarkers include a prognostic CD8+ T-cell gene signature for SLE and vasculitis, and SLE disease activity markers derived from gene modules.

Conclusions:

• Systematic biases are a major hurdle in gene expression biomarker development, necessitating robust validation.
• The type 1 interferon signature's role in SLE requires further clarification, despite ongoing trials for anti-interferon therapies.
• Validated gene expression signatures offer potential for improved diagnostics and prognostics in autoimmune rheumatic diseases.