Basophil activation test: A diagnostic, predictive and monitoring assay for allergen immunotherapy

For decades, the approach to clinical care has involved assessment of a fairly small set patients' signs and symptoms, sampled over short period time with limited attention given individual variations in aetiology pathophysiology. Subsequently, therapy is assigned predominantly "one shoe fits all" approach. Precision medicine approaches are now starting change ways test, treat develop new therapies for allergic immunological disorders (Figure 1). One first examples such personalized predictive enrichment Herceptin, approved by FDA 1998 HER2-positive metastatic breast cancer.1 The HER2 gene amplified 20%-30% early-stage cancers, measuring expression tumour, proper patient selection can be made use Herceptin. From 2000, percentage patients who underwent evaluation increased from 12% 94% along fivefold increase this targeted after 2004. Despite success story biomarker-driven treatment there been significant gap development companion diagnostics other indications, partly due difficulties either identifying or not knowing signals that induce biomarkers relevant predicting outcomes. To tackle patients, Hoffmann et al2 introduce “Time” as 3rd dimension, static induced biomarkers. They elegantly show, using functional basophil assay, how changes 3 weeks initiation predict long-term outcomes following subcutaneous immunotherapy (SCIT). authors monitored sensitivity response every three months during treatment, where they able monitor time. Basophil surface CD63 showed shortly start allergen (AIT) correlated based on vivo challenge. Further experimentation into mechanisms blocking factor antigen presentation assays humoral factors contributed reduction responses. Collection their data setting an open control arm further strengthens study real-world data, evidence playing more role decision-making regulatory agencies device, test drug approvals. Having objective measures critical disease decisions generally subjective reports measured Early identification will benefit continuation unmet need 2). activation (BAT) very effective monitoring tool. As biggest utility BAT before oral food challenges. Along these lines, referred challenge tube. value challenges well established wide variety allergens. In some cases, proven useful diagnostic venom allergies, even sensitive than intradermal skin testing.3 Moreover, responsiveness associated adverse effects arising immunotherapy. recent study, magnitude peanut correlation outcomes, those lower upregulation were likely achieve sustained unresponsiveness immunotherapy.4 determining allergens powerful tool when AIT immunomodulatory treatments, anti-IgE.5 (as CD-sens) shown reduced aeroallergens birch pollen timothy grass, insect venom.6 A dropin also reported omalizumab across range allergies including allergy peanut, cat Aspergillus. This finding accompanied spleen tyrosine kinase (Syk), enzyme essential IgE-mediated histamine release used potential biomarker efficacy omalizumab.7 only includes markers CD203c, but novel diamine oxidase (DAO), which bind intracellular basophils mast cells. earliest studies reporting grass was described 2015.8 superior levels fluorochrome-conjugated DAO combination markers. Additional have measure sublingual treatments. Following two years immunotherapy, both treatments suppressed pollen–induced indicated expression.9 Measurement indication threshold models. involving found time-dependent manner.10 decrease serum IgG antibodies level improvement symptoms. While previous confirmed efficacy, findings Hoffman al published issue highlight importance context “time” candidate outcome. current re-validates aforementioned expands understanding responses AIT. burden healthcare costs become high absence tools, especially approximately $11 billion annual medical rhinitis affects up 40% population United States, inconsistencies compliance observed 15% patients.11 hypothesize noncompliance result therapy. widely available better select cost expected. said this, however, still warranted fully implement routine practice. Disease part management many areas medicine: glucose diabetes, Holter arrhythmias thyroid hormone hypothyroidism, name few. Such monitoring, lived what it should disorders. An example overall lack antibody deficiency clinic, flow cytometry, progression combined immune deficiency. forms allergen-specific entering market, physicians guidance selection. This, turn, tie impact health extend pricing. Dr Shamji grants via Imperial College London ASIT Biotech.sa, ALK, Regeneron, Merck, Immune Tolerance Network, lecture fees ALK Allergopharma outside submitted work. Alpan, Layhadi, Li Sønder nothing disclose.