Detecting Changes in Mast Cell Numbers vs. Activation in Human Disease: A Roadblock for Current Biomarkers?

The pathophysiology of mast cell (MC)-driven disorders is diverse, ranging from localized reactions to systemic disorders caused by abnormal accumulation and activation in multi-organ systems. Prompt and accurate diagnosis is critically important, both for informing treatment and objective assessment of treatment outcomes. As new therapeutics are being developed to deplete MCs or silence them (e.g., by engaging inhibitory receptors that block activation), new biomarkers are needed that can distinguish between MC activation vs. burden. Serum tryptase is the gold standard for assessing both mast cell burden and activation; however, commercial tryptase assays have limitations related to timing of release, lack of discernment between inactive (α) and active (β) forms of tryptase, and interpatient variability of baseline levels. Alternative approaches to measuring MC activation include urinary mast cell mediators, flow cytometry-based assays or gene expression profiling. Additional markers of MC activation are needed for use in clinical diagnostics, to help selection of treatment of MC diseases, and for assessing outcomes of therapy. We review the spectrum of disorders with known or suspected MC contribution, describe the utility and limitations of current MC markers and assays, and discuss the need for new markers that can differentiate between MC activation and burden.