Salivary thiocyanate as a biomarker of Cystic Fibrosis Transmembrane Regulator function.

Abstract

Improved methods are needed to reliably assess CFTR function in vivo in light of recent therapeutic developments targeting the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. Saliva from patients with cystic fibrosis (CF) and healthy controls (HC) was studied using colorimetry and non-resonant 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 under-going 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, non-invasive 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. Moreover, samples from patients can be collected remotely, as they are stable and can be shipped in dry state. This insight may greatly facilitate assessments of CFTR modulator efficacy in individual pa-tients as well as development of new ones.

View details for DOI 10.1021/acs.analchem.9b01800

View details for PubMedID 31117414