Clinical inflammasome biomarkers: Progress and prospects

Pathological inflammasome signalling fuels low-grade inflammation and drives chronic disease. This underlying subclinical inflammation is notoriously difficult to define and measure at the molecular level. Although inflammasome inhibitors in clinical development hold immense therapeutic potential across a range of disease indications, their progress to market is hampered by a lack of inflammasome-specific biomarkers, posing some barriers to investment and clinical translation. While direct indicators of inflammasome signalling specifically report pathway activity, they are experimental, technically challenging, and their assays remain non-standardised. Meanwhile, routinely measured markers of inflammation (e.g. acute-phase reactants) are the current foundation of clinical trials for anti-inflammatory drug candidates, including trials of inflammasome inhibitors, as they are easily detectable and clinically well-validated. Their relationship to inflammasome signalling, however, is distal and confounded by other inflammatory signalling networks. Novel biomarker strategies are urgently required that faithfully and reproducibly reflect inflammasome signalling in humans. Here, we review the trade-off between inflammasome specificity and feasibility, weighing the opportunities and limitations of both proximal and distal biomarkers of inflammasome signalling.