Title:The Contribution of Transcriptomics to Biomarker Development in Systemic Vasculitis and SLE
Volume: 21
Issue: 17
Author(s): Shaun M. Flint, Eoin F. McKinney, Paul A. Lyons and Kenneth G.C. Smith
Affiliation:
Keywords:
Gene expression, biomarker, interferon, systemic lupus erythematosus, vasculitis.
Abstract: A small but increasing number of gene expression based biomarkers are becoming available for routine
clinical use, principally in oncology and transplantation. These underscore the potential of gene expression arrays
and RNA sequencing for biomarker development, but this potential has not yet been fully realized and most candidates
do not progress beyond the initial report. The first part of this review examines the process of gene expression-
based biomarker development, highlighting how systematic biases and confounding can significantly skew
study outcomes. Adequate validation in an independent cohort remains the single best means of protecting against
these concerns.
The second part considers gene-expression based biomarkers in Systemic Lupus Erythematosus (SLE) and systemic
vasculitis. The type 1 interferon inducible gene signature remains by far the most studied in autoimmune
rheumatic disease. While initially presented as an objective, blood-based biomarker of active SLE, subsequent research has shown that it
is not specific to SLE and that its association with disease activity is considerably more nuanced than first thought. Nonetheless, it is currently
under evaluation in ongoing trials of anti-interferon therapy. Other candidate markers of note include a prognostic CD8+ T-cell
gene signature validated in SLE and ANCA-associated vasculitis, and a disease activity biomarker for SLE derived from modules of
tightly correlated genes.
