Evaluation Of Th2 And Th17 Cytokine Levels In Serum From Asthmatics Using The High Sensitivity Quanterix Simoa HD-1 Platform

American Thoracic Society | May 15, 2016

Monica Gavala, Ph.D. Amgen
American Thoracic Society International Conference Abstracts - Posters
DOI: dx.doi.org/10.1016/j.jalz.2016.04.003

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Rationale: It is well established that the Th2 cytokines interleukin (IL)-5 and IL-13 are important mediators of asthma pathogensesis, and recent work has found IL-17A upregulated in a subset of asthmatics. As such, many biologics are emerging to target these cytokines directly to provide new therapeutic options for those who have suboptimal control with the current standard of care. These cytokines are readily detectable in bronchoscopy or sputum samples, especially after exposure to an exacerbation stimulus, but those are not practical sample types for monitoring a large number of patients involved in clinical trial studies. Peripheral blood is a more accessible sample that can be more uniformly collected and evaluated, but many key asthma-related cytokines are produced and consumed locally and circulate bewlow the limit of detection of conventional assays. Therefore, we investigated the capability of the Quanterix Simoa HD-1 to measure interleukin (IL)-5 , - 13, and -17A in serum samples to determine if increasing assay sensitivity will allow us to convincingly detect these cytokines at baseline. 

Methods: Banked serum samples from healthy (n=81) and asthmatic donors (n=123) acquired from various vendor sources from were evaluated for serum IL-5, IL-13 and IL-17A levels using validated kits on the Quanterix Simoa HD-1 platform following manufacturer's protocols. 

Results: The Simoa HD-1 assays were able to detect IL-5, IL-13 and IL-17A in the majority (greater than or equal to 98%) of serum samples tested. Differences between IL-5 and IL-17A between healthy and asthmatic donors were observed (p= 0.001 and p = 0.037, respectively), whereas no statistically significant difference in IL-13 was found (p=0.25). 

Conclusions: The ability to measure target cytokines in the periphery provides new opportunities ofr pharmacodynamic monitoring, and these circulating cytokines may serve as stratification biomarkers to identify asthma subsets that would benefit from emerging cytokine biologics.