{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T14:29:22Z","timestamp":1748269762672,"version":"3.40.5"},"reference-count":30,"publisher":"Walter de Gruyter GmbH","issue":"3","license":[{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2023-0774_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Testing of serum-free light chains kappa (\u03ba) and lambda (\u03bb), along with ratio (FLCR) is essential for the diagnosis and management of monoclonal gammopathies. Accurate clinical diagnosis depends upon appropriate local population reference intervals (RIs). This study examined the Saudi population for serum-free light chains and other immunoglobulins to establish RIs and to explore variations in the test results by using the International Federation for Clinical Chemistry and Laboratory Medicine\u2019s global protocol for harmonized implementation of RI study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0774_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>A total of 180 healthy Saudi adults were recruited. All serum samples were assayed using the Freelite reagents from the Binding Site. The variation in reference values attributable to sex, age, BMI, and region was calculated by ANOVA as a standard deviation ratio (SDR). The RIs for the\u00a0FLCR were derived by the parametric method and validated by using samples from patients with hypo- and hypergammaglobulinemia.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0774_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The new RIs for free \u03ba and FLCR were shifted to a higher side from the manufacturer-adapted RIs. Based on the SDR cutoff value (&gt;0.4), between-sex partition RIs were not required for all analytes except IgM. Validation using patients with hypo- or hypergammaglobulinemia and without multiple myeloma, was all within the new RI. BMI, smoking, and exercise were not relevant sources of variation for any analyte.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2023-0774_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Locally derived RIs for free light chains and immunoglobulins analytes specific for Saudis were established after careful consideration of various factors. These RIs were more reliable than those provided as guidance by the manufacturer, or from other countries, for appropriate classification and prediction of disease progression for Saudi patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2023-0774","type":"journal-article","created":{"date-parts":[[2023,10,3]],"date-time":"2023-10-03T15:10:39Z","timestamp":1696345839000},"page":"522-529","source":"Crossref","is-referenced-by-count":2,"title":["Establishment of reference intervals for free light chains and immunoglobulins in Saudi population"],"prefix":"10.1515","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6504-9559","authenticated-orcid":false,"given":"Anwar","family":"Borai","sequence":"first","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard , Riyadh , Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6039-4537","authenticated-orcid":false,"given":"Kiyoshi","family":"Ichihara","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences , Yamaguchi University Graduate School of Medicine , Ube , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waleed","family":"Tamimi","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard , Riyadh , Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abdulaziz","family":"Masaud","sequence":"additional","affiliation":[{"name":"King Abdullah International Medical Research Center (KAIMRC), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), King Abdulaziz Medical City, Ministry of National Guard , Riyadh , Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samia","family":"Sobki","sequence":"additional","affiliation":[{"name":"Central Military Laboratory & Blood Bank , Prince Sultan Military Medical City , Riyadh , Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2023,10,4]]},"reference":[{"key":"2024012313272683835_j_cclm-2023-0774_ref_001","doi-asserted-by":"crossref","unstructured":"Kyle, RA. Sequence of testing for monoclonal gammopathies. Arch Pathol Lab Med 1999;123:114\u20138. https:\/\/doi.org\/10.5858\/1999-123-0114-sotfmg.","DOI":"10.5858\/1999-123-0114-SOTFMG"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_002","doi-asserted-by":"crossref","unstructured":"Bradwell, AR, Carr-Smith, HD, Mead, GP, Harvey, TC, Drayson, MT. Serum test for assessment of patients with Bence Jones myeloma. Lancet 2003;361:489\u201391. https:\/\/doi.org\/10.1016\/s0140-6736(03)12457-9.","DOI":"10.1016\/S0140-6736(03)12457-9"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_003","doi-asserted-by":"crossref","unstructured":"Palladini, G, Russo, P, Bosoni, T, Verga, L, Sarais, G, Lavatelli, F, et al.. Identification of amyloidogenic light chains requires the combination of serum-free light chain assay with immunofixation of serum and urine. Clin Chem 2009;55:499\u2013504. https:\/\/doi.org\/10.1373\/clinchem.2008.117143.","DOI":"10.1373\/clinchem.2008.117143"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_004","unstructured":"World Health Organization. Cancer Country Profile, 50. World Health Organization; 2014:1\u20134 pp."},{"key":"2024012313272683835_j_cclm-2023-0774_ref_005","unstructured":"Bazarbashi, S, Al Eid, H, Minguet, J. Cancer incidence in Saudi Arabia: 2012 data from the Saudi cancer registry. Asian Pac J Cancer Prev 2017;18:2437\u201344. https:\/\/doi.org\/10.22034\/APJCP.2017.18.9.2437."},{"key":"2024012313272683835_j_cclm-2023-0774_ref_006","doi-asserted-by":"crossref","unstructured":"Alaskar, A, Alsaeed, A, Alsharif, F, Alhashmi, H, Alghamdi, M. Multiple myeloma in Saudi Arabia: consensus of the Saudi lymphoma\/myeloma group. J Appl Hematol 2019;10:37\u201344. https:\/\/doi.org\/10.4103\/joah.joah_62_18.","DOI":"10.4103\/joah.joah_62_18"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_007","doi-asserted-by":"crossref","unstructured":"Katzmann, JA, Clark, RJ, Abraham, RS, Bryant, S, Lymp, JF, Bradwell, AR, et al.. Serum reference intervals and diagnostic ranges for free kappa and free lambda immunoglobulin light chains: relative sensitivity for detection of monoclonal light chains. Clin Chem 2002;48:1437\u201344. https:\/\/doi.org\/10.1093\/clinchem\/48.9.1437.","DOI":"10.1093\/clinchem\/48.9.1437"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_008","doi-asserted-by":"crossref","unstructured":"Dispenzieri, A, Kyle, R, Merlini, G, Miguel, JS, Ludwig, H, Hajek, R, et al.. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia 2009;23:215\u201324. https:\/\/doi.org\/10.1038\/leu.2008.307.","DOI":"10.1038\/leu.2008.307"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_009","doi-asserted-by":"crossref","unstructured":"Fink, SL, Wener, MH, Rudolf, JW, Nwosu, A, Tacker, DH, Kadkhoda, K, et al.. A\u00a0universal reference interval for serum immunoglobulins free light chains may be outdated. Clin Chem Lab Med 2023;61:e229\u201332. https:\/\/doi.org\/10.1515\/cclm-2023-0473.","DOI":"10.1515\/cclm-2023-0473"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_010","doi-asserted-by":"crossref","unstructured":"Zemlin, AE, Rensburg, MA, Ipp, H, Germishuys, JJ, Erasmus, RT. Verification of serum reference intervals for free light chains in a local South African population. J Clin Pathol 2013;66:992\u20135. https:\/\/doi.org\/10.1136\/jclinpath-2013-201511.","DOI":"10.1136\/jclinpath-2013-201511"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_011","doi-asserted-by":"crossref","unstructured":"Liang, YF, Chen, WM, Wang, QT, Zhai, YH, Yang, YJ, Liu, JY, et al.. Establishment and validation of serum free light chain reference intervals in an ethnic Chinese population. Clin Lab 2014;60:193\u20138. https:\/\/doi.org\/10.7754\/clin.lab.2013.130129.","DOI":"10.7754\/Clin.Lab.2013.130129"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_012","doi-asserted-by":"crossref","unstructured":"Morales-Garcia, LJ, Pacheco-Delgado, MS. Serum free light chain reference intervals in an Optilite and their influence on clinical guidelines. Clin Biochem 2021;92:54\u201360. https:\/\/doi.org\/10.1016\/j.clinbiochem.2021.02.008.","DOI":"10.1016\/j.clinbiochem.2021.02.008"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_013","doi-asserted-by":"crossref","unstructured":"Borai, A, Ichihara, K, Al Masaud, A, Tamimi, W, Bahijri, S, Armbuster, D, et al.. Establishment of reference intervals of clinical chemistry analytes for the adult population in Saudi Arabia: a study conducted as a part of the IFCC global study on reference values. Clin Chem Lab Med 2016;54:843\u201355. https:\/\/doi.org\/10.1515\/cclm-2015-0490.","DOI":"10.1515\/cclm-2015-0490"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_014","doi-asserted-by":"crossref","unstructured":"Borai, A, Ichihara, K, Masaud, A, Tamimi, W, Bahijri, S, Armbuster, D, et al.. Establishment of reference intervals for immunoassay analytes of adult population in Saudi Arabia. Clin Chem Lab Med 2020;58:1302\u201313. https:\/\/doi.org\/10.1515\/cclm-2019-1049.","DOI":"10.1515\/cclm-2019-1049"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_015","doi-asserted-by":"crossref","unstructured":"Borai, A, Ichihara, K, Bahijri, S, Almasoud, A, Tamimi, W, Abdulhadi, W, et al.. Establishment of reference intervals for hematological parameters of adult population in the western region of Saudi Arabia. PLoS One 2023;18:e0281494. https:\/\/doi.org\/10.1371\/journal.pone.0281494.","DOI":"10.1371\/journal.pone.0281494"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_016","doi-asserted-by":"crossref","unstructured":"Ozarda, Y, Ichihara, K, Barth, JH, Klee, G, Committee on Reference I, Decision Limits IFfCC, et al.. Protocol and standard operating procedures for common use in a worldwide multicenter study on reference values. Clin Chem Lab Med 2013;51:1027\u201340. https:\/\/doi.org\/10.1515\/cclm-2013-0249.","DOI":"10.1515\/cclm-2013-0249"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_017","doi-asserted-by":"crossref","unstructured":"Ichihara, K, Kawai, T. Determination of reference intervals for 13 plasma proteins based on IFCC international reference preparation (CRM470) and NCCLS proposed guideline (C28-P,1992): trial to select reference individuals by results of screening tests and application of maximal likelihood method. J Clin Lab Anal 1996;10:110\u20137. https:\/\/doi.org\/10.1002\/(sici)1098-2825(1996)10:2<110::aid-jcla9>3.0.co;2-g.","DOI":"10.1002\/(SICI)1098-2825(1996)10:2<110::AID-JCLA9>3.3.CO;2-A"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_018","doi-asserted-by":"crossref","unstructured":"Ichihara, K, Itoh, Y, Lam, CW, Poon, PM, Kim, JH, Kyono, H, et al.. Sources of variation of commonly measured serum analytes in 6 Asian cities and consideration of common reference intervals. Clin Chem 2008;54:356\u201365. https:\/\/doi.org\/10.1373\/clinchem.2007.091843.","DOI":"10.1373\/clinchem.2007.091843"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_030","doi-asserted-by":"crossref","unstructured":"Ichihara, K, Boyd, J, IFCC Committee on Reference Intervals and Decision Limits (C-RIDL). An appraisal of statistical procedures used in derivation of reference intervals. Clin Chem Lab Med 2010;48:1537\u201351. https:\/\/doi.org\/10.1515\/CCLM.2010.319. 21062226","DOI":"10.1515\/CCLM.2010.319"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_019","doi-asserted-by":"crossref","unstructured":"Campbell, L, Simpson, D, Shields, A, Ferry, B, Ramasamy, K, Sadler, R. In-house age-specific reference ranges for free light chains measured on the SPAPlus(R) analyser. Ann Clin Biochem 2020;57:138\u201343. https:\/\/doi.org\/10.1177\/0004563219899421.","DOI":"10.1177\/0004563219899421"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_020","doi-asserted-by":"crossref","unstructured":"Tarbiah, N, Todd, I, Tighe, PJ, Fairclough, LC. Cigarette smoking differentially affects immunoglobulin class levels in serum and saliva: an investigation and review. Basic Clin Pharmacol Toxicol 2019;125:474\u201383. https:\/\/doi.org\/10.1111\/bcpt.13278.","DOI":"10.1111\/bcpt.13278"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_021","doi-asserted-by":"crossref","unstructured":"McMillan, SA, Douglas, JP, Archbold, GP, McCrum, EE, Evans, AE. Effect of low to moderate levels of smoking and alcohol consumption on serum immunoglobulin concentrations. J Clin Pathol 1997;50:819\u201322. https:\/\/doi.org\/10.1136\/jcp.50.10.819.","DOI":"10.1136\/jcp.50.10.819"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_022","doi-asserted-by":"crossref","unstructured":"Bawua, SA, Ichihara, K, Keatley, R, Arko-Mensah, J, Ayeh-Kumi, PF, Erasmus, R, et al.. Derivation of sex and age-specific reference intervals for clinical chemistry analytes in healthy Ghanaian adults. Clin Chem Lab Med 2022;60:1426\u201339. https:\/\/doi.org\/10.1515\/cclm-2022-0293.","DOI":"10.1515\/cclm-2022-0293"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_023","doi-asserted-by":"crossref","unstructured":"Shah, SAV, Ichihara, K, Dherai, AJ, Ashavaid, TF. Reference intervals for 33 biochemical analytes in healthy Indian population: C-RIDL IFCC initiative. Clin Chem Lab Med 2018;56:2093\u2013103. https:\/\/doi.org\/10.1515\/cclm-2018-0152.","DOI":"10.1515\/cclm-2018-0152"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_024","doi-asserted-by":"crossref","unstructured":"Omuse, G, Ichihara, K, Maina, D, Hoffman, M, Kagotho, E, Kanyua, A, et al.. Determination of reference intervals for common chemistry and immunoassay tests for Kenyan adults based on an internationally harmonized protocol and up-to-date statistical methods. PLoS One 2020;15:e0235234. https:\/\/doi.org\/10.1371\/journal.pone.0235234.","DOI":"10.1371\/journal.pone.0235234"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_025","doi-asserted-by":"crossref","unstructured":"Evgina, S, Ichihara, K, Ruzhanskaya, A, Skibo, I, Vybornova, N, Vasiliev, A, et al.. Establishing reference intervals for major biochemical analytes\u00a0for the Russian population: a research conducted as a part of the IFCC global study on reference values. Clin Biochem 2020;81:47\u201358. https:\/\/doi.org\/10.1016\/j.clinbiochem.2020.04.001.","DOI":"10.1016\/j.clinbiochem.2020.04.001"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_026","doi-asserted-by":"crossref","unstructured":"Taneja, V. Sex hormones determine immune response. Front Immunol 2018;9:1931. https:\/\/doi.org\/10.3389\/fimmu.2018.01931.","DOI":"10.3389\/fimmu.2018.01931"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_027","doi-asserted-by":"crossref","unstructured":"Ichihara, K, Ceriotti, F, Tam, TH, Sueyoshi, S, Poon, PM, Thong, ML, et al.. The Asian project for collaborative derivation of reference intervals: (1) strategy and major results of standardized analytes. Clin Chem Lab Med 2013;51:1429\u201342. https:\/\/doi.org\/10.1515\/cclm-2012-0421.","DOI":"10.1515\/cclm-2012-0421"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_028","doi-asserted-by":"crossref","unstructured":"Murray, D, Dispenzieri, A, Kumar, S, Gill, H, Vachon, C, Snyder, M, et al.. Free light chain assay drift: potential for misdiagnosis? J Appl Lab Med 2020;5:1411\u20133. https:\/\/doi.org\/10.1093\/jalm\/jfaa093.","DOI":"10.1093\/jalm\/jfaa093"},{"key":"2024012313272683835_j_cclm-2023-0774_ref_029","doi-asserted-by":"crossref","unstructured":"Rindlisbacher, B, Schild, C, Egger, F, Bacher, VU, Pabst, T, Leichtle, A, et al.. Serum free light chain assay: shift toward a higher kappa\/lambda ratio. J Appl Lab Med 2020;5:114\u201325. https:\/\/doi.org\/10.1093\/jalm.2019.029330.","DOI":"10.1093\/jalm.2019.029330"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-0774\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-0774\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T13:29:15Z","timestamp":1706016555000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyter.com\/document\/doi\/10.1515\/cclm-2023-0774\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,4]]},"references-count":30,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2023,12,13]]},"published-print":{"date-parts":[[2024,2,26]]}},"alternative-id":["10.1515\/cclm-2023-0774"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2023-0774","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"type":"print","value":"1434-6621"},{"type":"electronic","value":"1437-4331"}],"subject":[],"published":{"date-parts":[[2023,10,4]]}}}