Immune Tolerance Network (ITN) investigators Stephen Durham, MD and Guy Scadding, MD from the Imperial College London conducted a pilot study in collaboration with ALK Abello to evaluate a technique to reproducibly measure time-dependent immunologic responses to allergens using nasal secretion collections. Results from this pilot study are published in the Journal of Immunological Methods [see here].
A key cornerstone of each ITN trial is incorporating a set of genetic and cellular assays to better understand treatment response, to establish surrogate markers of efficacy, and to explore mechanisms of immune tolerance. Trials that evaluate therapeutics for allergic diseases often use allergen challenges (direct administration of the allergen of interest) to evaluate a patient’s clinical and cellular response to allergens; however, methods to measure such responses are often variable in practicality and quality.
In this pilot, twenty grass pollen-allergic subjects underwent nasal challenges with Timothy grass extract. Investigators collected nasal fluid using sponges before challenge and at multiple time points within 6 hours post-challenge. Cellular analyses revealed detailed, time-dependent cytokine responses to grass pollen challenge. Patterns of inflammatory mediators correlated well with clinical symptoms, and convinced ITN investigators that measurement of cytokines in nasal secretions post nasal challenge should be one of the main mechanistic assays in the ITN043AD GRASS study (Long Term Effects of Sublingual Grass Therapy). This technique has a number of advantages over other specimen collection methods, namely the ability to conduct repeated assessments at the relevant site (nose) over a time course with good tolerability (compared to nasal biopsies, e.g.), and thus will better facilitate the evaluation of allergen immunotherapy and its impact on immune responses and tolerance.