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 colorime...
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| Veröffentlicht in: | Analytical chemistry (Washington) 2019-06, Vol.91 (12), p.7929-7934 |
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| container_title | Analytical chemistry (Washington) |
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| creator | Malkovskiy, Andrey V Yacob, Alexander A Dunn, Colleen E Zirbes, Jacquelyn M Ryan, Sean P Bollyky, Paul L Rajadas, Jayakumar Milla, Carlos E |
| description | 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. |
| doi_str_mv | 10.1021/acs.analchem.9b01800 |
| format | Article |
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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.</description><identifier>ISSN: 0003-2700</identifier><identifier>EISSN: 1520-6882</identifier><identifier>DOI: 10.1021/acs.analchem.9b01800</identifier><identifier>PMID: 31117414</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Analytical chemistry ; Assessments ; Biomarkers ; Chemistry ; Colorimetry ; Conductance ; Cystic fibrosis ; Cystic fibrosis transmembrane conductance regulator ; Drug delivery ; Modulators ; Raman spectroscopy ; Saliva ; Thiocyanates ; Vibrations</subject><ispartof>Analytical chemistry (Washington), 2019-06, Vol.91 (12), p.7929-7934</ispartof><rights>Copyright American Chemical Society Jun 18, 2019</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a376t-ab4e804c7240c651842b2ad71dbc2498e6e475b7b7b995684ac9800d2ee11393</citedby><cites>FETCH-LOGICAL-a376t-ab4e804c7240c651842b2ad71dbc2498e6e475b7b7b995684ac9800d2ee11393</cites><orcidid>0000-0002-5648-8602</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.analchem.9b01800$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.analchem.9b01800$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31117414$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Malkovskiy, Andrey V</creatorcontrib><creatorcontrib>Yacob, Alexander A</creatorcontrib><creatorcontrib>Dunn, Colleen E</creatorcontrib><creatorcontrib>Zirbes, Jacquelyn M</creatorcontrib><creatorcontrib>Ryan, Sean P</creatorcontrib><creatorcontrib>Bollyky, Paul L</creatorcontrib><creatorcontrib>Rajadas, Jayakumar</creatorcontrib><creatorcontrib>Milla, Carlos E</creatorcontrib><title>Salivary Thiocyanate as a Biomarker of Cystic Fibrosis Transmembrane Regulator Function</title><title>Analytical chemistry (Washington)</title><addtitle>Anal. Chem</addtitle><description>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.</description><subject>Analytical chemistry</subject><subject>Assessments</subject><subject>Biomarkers</subject><subject>Chemistry</subject><subject>Colorimetry</subject><subject>Conductance</subject><subject>Cystic fibrosis</subject><subject>Cystic fibrosis transmembrane conductance regulator</subject><subject>Drug delivery</subject><subject>Modulators</subject><subject>Raman spectroscopy</subject><subject>Saliva</subject><subject>Thiocyanates</subject><subject>Vibrations</subject><issn>0003-2700</issn><issn>1520-6882</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><recordid>eNp9kM9LwzAUx4Mobk7_A5GAFy-d76Vp0x51OBUEQQceS5pmLrNdZtIK--9N2Y-DB8nhXT7f78v7EHKJMEZgeCuVH8uVrNVCN-O8BMwAjsgQEwZRmmXsmAwBII6YABiQM--XAIiA6SkZxIgoOPIh-XiXtfmRbkNnC2PVJjS2mkpPJb03tpHuSztq53Sy8a1RdGpKZ73xdObkyje6KcPU9E1_drVsraPTbqVaY1fn5GQua68vdnNEZtOH2eQpenl9fJ7cvUQyFmkbyZLrDLgSjINKE8w4K5msBFalYjzPdKq5SEoRXp4nacalysOdFdMaMc7jEbnZ1q6d_e60b4vGeKXrOvzKdr5gLGYIXKQ9ev0HXdrOBYE9xVOWcMF5oPiWUuFO7_S8WDsTNGwKhKL3XgTvxd57sfMeYle78q5sdHUI7UUHALZAHz8s_rfzF1C3kQQ</recordid><startdate>20190618</startdate><enddate>20190618</enddate><creator>Malkovskiy, Andrey V</creator><creator>Yacob, Alexander A</creator><creator>Dunn, Colleen E</creator><creator>Zirbes, Jacquelyn M</creator><creator>Ryan, Sean P</creator><creator>Bollyky, Paul L</creator><creator>Rajadas, Jayakumar</creator><creator>Milla, Carlos E</creator><general>American Chemical Society</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QF</scope><scope>7QO</scope><scope>7QQ</scope><scope>7SC</scope><scope>7SE</scope><scope>7SP</scope><scope>7SR</scope><scope>7TA</scope><scope>7TB</scope><scope>7TM</scope><scope>7U5</scope><scope>7U7</scope><scope>7U9</scope><scope>8BQ</scope><scope>8FD</scope><scope>C1K</scope><scope>F28</scope><scope>FR3</scope><scope>H8D</scope><scope>H8G</scope><scope>H94</scope><scope>JG9</scope><scope>JQ2</scope><scope>KR7</scope><scope>L7M</scope><scope>L~C</scope><scope>L~D</scope><scope>P64</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5648-8602</orcidid></search><sort><creationdate>20190618</creationdate><title>Salivary Thiocyanate as a Biomarker of Cystic Fibrosis Transmembrane Regulator Function</title><author>Malkovskiy, Andrey V ; 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Chem</addtitle><date>2019-06-18</date><risdate>2019</risdate><volume>91</volume><issue>12</issue><spage>7929</spage><epage>7934</epage><pages>7929-7934</pages><issn>0003-2700</issn><eissn>1520-6882</eissn><abstract>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. 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| subjects | Analytical chemistry Assessments Biomarkers Chemistry Colorimetry Conductance Cystic fibrosis Cystic fibrosis transmembrane conductance regulator Drug delivery Modulators Raman spectroscopy Saliva Thiocyanates Vibrations |
| title | Salivary Thiocyanate as a Biomarker of Cystic Fibrosis Transmembrane Regulator Function |
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