Salivary Thiocyanate as a Biomarker of Cystic Fibrosis Transmembrane Regulator Function

Improved methods are needed to reliably assess Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) function in vivo in light of recent therapeutic developments targeting the CFTR protein. Oral fluid from patients with cystic fibrosis (CF) and healthy controls (HCs) were studied using colorimetry and nonresonant Raman spectroscopy. Colorimetry experiments showed only a 36% decrease in thiocyanate (SCN^-) concentration, but a sharp Raman peak at 2068 cm^-1, attributable to (SCN^-) vibrations, normalized to C-H peak, was on average 18 times higher for HC samples. Samples from patients undergoing treatment with CFTR modulators including ivacaftor, lumacaftor, and tezacaftor showed a high normalized peak in response to therapy. The peak intensity was consistent in longitudinal samples from single donors and in stored samples. The Raman peak ratio is a more sensitive, convenient, noninvasive biomarker for assessments of the therapeutic efficacy of drugs targeting CFTR and provides a value that is in much better agreement with theoretical expectations of saliva SCN^- concentrations compared to colorimetry. This insight may greatly facilitate assessments of CFTR modulator efficacy in individual patients.