Host transcriptional analysis to improve the diagnosis of group A streptococcal pharyngitis

Yu, J.; Tychsen, E.; Yang, W.; Mariani, T. J.; Bhattacharya, S.; Falsey, A. R.; Topham, D. J.; Storch, G. A.

Current diagnostic methods used to evaluate patients with pharyngitis for the presence of group A Streptococcus (GAS) do not discriminate between acute infection and asymptomatic carriage, potentially resulting in overuse of antibiotics. We hypothesized that host response as measured by the transcriptomic profile of peripheral blood leukocytes could make this distinction, and could also distinguish between GAS and viral infection. We used RNA sequencing to generate whole blood transcriptomes from 37 children, including 10 with acute GAS pharyngitis, 5 with asymptomatic GAS carriage, 3 with adenoviral pharyngitis, 3 with pharyngitis of unknown etiology, and 16 asymptomatic children negative for GAS. Transcriptional profiles from children with symptomatic GAS, GAS carriage, symptomatic adenoviral pharyngitis, and controls were each distinct. Of 15,185 genes with analyzable sequence, 1357 (8.9%) were differentially expressed in the children with symptomatic GAS compared to those with asymptomatic carriage, and 1336 (8.8%) compared to symptomatic adenovirus infection. A panel of 13 genes distinguished between children with acute GAS and all others with 91% accuracy. The gene encoding CD177, a marker of neutrophil activation, had a 152-fold increase in expression in children with acute GAS, and is a potential diagnostic biomarker. We conclude that measurement of host response is highly promising to improve the diagnosis of GAS pharyngitis and could help limit unnecessary antibiotic use.