{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T08:38:33Z","timestamp":1789115913502,"version":"build-2803163510"},"reference-count":25,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2026-0510_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Ceruloplasmin (Cp) and non\u2013ceruloplasmin-bound copper (NCC) are measured when evaluating liver disease and disorders of copper (Cu) metabolism. Cp mass concentration is typically determined by immunoassays that detect both apo- and holoceruloplasmin. In contrast, enzymatic assays measure Cp ferroxidase activity and are therefore specific for holoceruloplasmin. Their clinical use has been limited by the absence of a method to convert enzyme activity to molar Cp concentration and to estimate\u00a0NCC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0510_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Cp ferroxidase activity and serum Cu concentrations were measured in a training dataset (n=924) to define their linear relationship and derive a conversion factor based on the stoichiometry of six Cu atoms per Cp molecule. This factor was applied to an independent validation cohort (n=12,635). Cp activity, Cp mass concentration, and serum Cu were compared, and reference intervals for Cp activity and NCC were established.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0510_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The calibration of Cp activity assay against Cu concentration yielded a conversion factor of 0.0030 for expressing Cp activity in molar units. Reference intervals for Cp activity were 1.5\u20133.7\u202f\u03bcmol\/L in males and 1.6\u20134.3\u202f\u03bcmol\/L in females. Comparison with nephelometric Cp measurements demonstrated a positive bias and evidence of analytical interference in a subset of samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2026-0510_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We describe a method to convert Cp ferroxidase activity to molar concentration and demonstrate its application in a large clinical cohort. This approach enables estimation of NCC, although with considerable uncertainty, and establishment of reference intervals using activity-based measurements. Measurement of Cp by enzymatic activity provides a cost-effective and analytically robust alternative to immunoassays, with advantages in specificity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2026-0510","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T07:55:55Z","timestamp":1789113355000},"source":"Crossref","is-referenced-by-count":0,"title":["Stoichiometric calibration of ceruloplasmin activity with copper enables molar quantification and has implications for the estimation of non-ceruloplasmin-bound copper"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-8455","authenticated-orcid":false,"given":"Alexandra M.","family":"Kane","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt T.K.","family":"Giuliani","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Coogan","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Sanders","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Ruddell","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology , New South Wales Health Pathology, New South Wales Health , Newcastle , NSW , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7173-1634","authenticated-orcid":false,"given":"Matthew","family":"Burke","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-3995","authenticated-orcid":false,"given":"Carel J.","family":"Pretorius","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4929-0929","authenticated-orcid":false,"given":"Jacobus P.J.","family":"Ungerer","sequence":"additional","affiliation":[{"name":"Department of Chemical Pathology, Pathology Queensland, Queensland Health , Brisbane , QLD , Australia"},{"name":"University of Queensland, School of Medicine , Brisbane , QLD , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"2026091107553999214_j_cclm-2026-0510_ref_001","doi-asserted-by":"crossref","unstructured":"Hellman, NE, Gitlin, JD. 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