{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T03:59:43Z","timestamp":1781582383372,"version":"3.54.5"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2016,5,1]],"date-time":"2016-05-01T00:00:00Z","timestamp":1462060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100005674","name":"Cystinosis Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005674","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,5,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>Cystine determination is a critical biochemical test for the diagnosis and therapeutic monitoring of the lysosomal storage disease cystinosis. The classical mixed-leukocyte cystine assay requires prompt specialized recovery\/isolation following blood drawing, providing cystine concentrations normalized to total protein from assorted types of white blood cells, each with varying cystine content.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>We present a new workflow for cystine determination using immunomagnetic granulocyte purification, and new reference ranges established from 47 patient and 27 obligate heterozygote samples assayed. Samples were collected in acid-citrate dextrose tubes and their stability was proven to allow for overnight shipping before analysis. Cystine was quantified by LC-MS\/MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>The new method was reproducible (&amp;lt;15% root mean square error) and specific, assaying purified granulocytes from blood samples that no longer required immediate preparation and therefore allowing for up to 30 h before processing. There was a nearly a 2-fold increase in the therapeutic target (1.9 nmol half-cystine\/mg protein) range, established using distributions of patient, obligate heterozygote, and control samples. The 2.5\u201397.5 percentile ranges (\u22122 SD to +2 SD around mean) for these cohorts were 0.67\u20136.05 nmol\/mg protein for patients, 0.33\u20131.35 nmol\/mg protein for obligate heterozygotes, and 0.09\u20130.35 nmol\/mg protein for controls.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>The intracellular cystine determination method using immunopurified granulocytes followed by LC-MS\/MS analysis improves the inherent variability of mixed leukocyte analysis and eliminates the need for immediate sample preparation following blood draw.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1373\/clinchem.2015.252494","type":"journal-article","created":{"date-parts":[[2016,3,15]],"date-time":"2016-03-15T23:48:56Z","timestamp":1458085736000},"page":"766-772","source":"Crossref","is-referenced-by-count":19,"title":["Diagnosis and Monitoring of Cystinosis Using Immunomagnetically Purified Granulocytes"],"prefix":"10.1093","volume":"62","author":[{"given":"Ilya","family":"Gertsman","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wynonna S","family":"Johnson","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor","family":"Nishikawa","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon A","family":"Gangoiti","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Holmes","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A","family":"Barshop","sequence":"first","affiliation":[{"name":"Biochemical Genetics and Metabolomics Laboratory, Department of Pediatrics, University of California, San Diego, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2016,5,1]]},"reference":[{"key":"2020022605330936200_B1","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1056\/NEJMra020552","article-title":"Cystinosis","volume":"347","author":"Gahl","year":"2002","journal-title":"N Engl J Med"},{"key":"2020022605330936200_B2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/ng0695-246","article-title":"Linkage of the gene for cystinosis to markers on the short arm of chromosome 17. 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