Home Medicine Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis
Article
Licensed
Unlicensed Requires Authentication

Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis

  • Emine Feyza Yurt ORCID logo EMAIL logo , Medine Alpdemir ORCID logo and Mehmet Şeneş ORCID logo
Published/Copyright: August 21, 2025
Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 63 Issue 12

Abstract

Objectives

Measurement uncertainty (MU) plays an important role in the interpretation of laboratory results, but data on serum proteins analyzed by immunoturbidimetry according to ISO/TS 20914 are limited.

Methods

MU of 11 serum proteins, including CRP, RF, ASO, IgG, IgA, IgM, C3, C4, ceruloplasmin, transferrin, and β2-microglobulin, were estimated using 1-year internal quality control (IQC) data obtained from Roche Cobas analyzers. MU was calculated using uncertainty and calibrator uncertainty according to ISO/TS 20914, assuming negligible deviation from external quality assessment data. Analytical performance specification (APS) models were selected according to the EFLM APS selection criteria, and maximum allowable uncertainty (MAU) values were determined based on sources such as EFLM models and literature.

Results

IgA and RF were the only two analytes that met the required and minimum MAU values, respectively, at both IQC levels. MU values for CRP, ceruloplasmin, transferrin, and β2-microglobulin exceeded targets at both levels. MU for C3, C4, IgG, and IgM exceeded the minimum MAU at IQC1 but remained acceptable at IQC2. MU values for ASO were calculated as 10.01 and 7.22 % but could not be evaluated due to a lack of reference data. Assay precision should be improved for CRP, IgG, IgM, ceruloplasmin, transferrin, and β2-microglobulin. Use of updated calibration materials for CRP may help reduce MU.

Conclusions

Maintaining acceptable precision over a long period remains a challenge for serum proteins analyzed by immunoturbidimetry, highlighting the need for methodological improvements and stricter quality monitoring. In this context, MU assessment is crucial.

Keywords: measurement uncertainty; immunoturbidimetry; serum proteins; ISO/TS 20914; analytical performance specifications; clinical laboratory quality
Corresponding author: Emine Feyza Yurt, MD, PhD, Departmant of Medical Biochemistry, Ankara Training and Research Hospital, Hacettepe, Ulucanlar, 06230, Ankara, Türkiye, E-mail:

  1. Research ethics: The study received approval from the clinical research ethics committee of Ankara Training and Research Hospital (Decision Date and Number: Feb 05, 2025/386).

  2. Informed consent: Not applicable.

  3. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  4. Use of Large Language Models, AI and Machine Learning Tools: Chat GPT (Open AI) was used for language correction.

  5. Conflict of interest: The authors state no conflict of interest.

  6. Research funding: None declared.

  7. Data availability: Not applicable.

References

1. Coskun, A, Theodorsson, E, Oosterhuis, WP, Sandberg, S. European federation of clinical chemistry and laboratory medicine task and finish group on practical approach to measurement uncertainty. Measurement uncertainty for practical use. Clin Chim Acta 2022;531:352–60. https://doi.org/10.1016/j.cca.2022.04.1003.Search in Google Scholar PubMed

2. International Organization for Standardization. ISO/TS 20914:2019. In: Medical laboratories- practical guidance for the estimation of measurement uncertainty. Geneva: ISO; 2019.Search in Google Scholar

3. Alpdemir, MF, Tutar, S, Alpdemir, M. Evaluation of measurement uncertainty in direct and estimated serum osmolality according to ISO/TS 20914: implications for clinical diagnostics. Scand J Clin Lab Invest 2025;85:184–9. https://doi.org/10.1080/00365513.2025.2487988.Search in Google Scholar PubMed

4. Blirup-Jensen, S. Protein standardization III: method optimization – basic principles for quantitative determination of human serum proteins on automated instruments based on turbidimetry or nephelometry. Clin Chem Lab Med 2001;39:1098–109. https://doi.org/10.1515/cclm.2001.175.Search in Google Scholar PubMed

5. Ceriotti, F, Fernandez-Calle, P, Klee, GG, Nordin, G, Sandberg, S, Streichert, T, et al.. Criteria for assigning laboratory measurands to models for analytical performance specifications defined in the 1st EFLM strategic conference. Clin Chem Lab Med 2017;55:189–94. https://doi.org/10.1515/cclm-2016-0091.Search in Google Scholar PubMed

6. Jiménez, CV. Usefulness of reference limits and evaluation of significant differences: an example of the biological variation of serum rheumatoid factors. Ann Biol Clin 1994;52:529–33.Search in Google Scholar

7. Centers for Medicare and Medicaid Services (CMS). Clinical Laboratory improvement amendments of 1988 (CLIA) proficiency testing regulations related to analytes and acceptable performance. Fed Regist 2022;87:41194–242. Available from: https://www.federalregister.gov/documents/2022/07/11/2022-14513/clinical-laboratory-improvement-amendments-of-1988-clia-proficiency-testing-regulations-related-to? [Accessed May 2025].Search in Google Scholar

8. Braga, F, Panteghini, M. Performance specifications for measurement uncertainty of common biochemical measurands according to Milan models. Clin Chem Lab Med 2021;59:1362–8. https://doi.org/10.1515/cclm-2021-0170.Search in Google Scholar PubMed

9. Braga, F, Panteghini, M. Derivation of performance specifications for uncertainty of serum C-reactive protein measurement according to the Milan model 3 (state of the art). Clin Chem Lab Med 2020;58:e263–5. https://doi.org/10.1515/cclm-2020-0532.Search in Google Scholar PubMed

10. Aarsand, AK, Fernandez-Calle, P, Webster, C, Jonker, N, Diaz-Garzon, J, Coskun, A, et al.. The EFLM biological variation database. Available from: https://biologicalvariation.eu/ [Accessed April 2025].Search in Google Scholar

11. Nurlu, N, Çat, A, Uçar, KT. Measurement uncertainty in clinical chemistry: ISO 20914 versus Nordtest or intermediate precision versus bias. Scand J Clin Lab Invest 2024;84:147–53. https://doi.org/10.1080/00365513.2024.2338738.Search in Google Scholar PubMed

12. Çubukçu, HC, Yavuz, Ö, Devrim, E. Uncertainty of measurement for 14 immunoassay analytes: application to laboratory result interpretation. Scand J Clin Lab Invest 2019;79:117–22. https://doi.org/10.1080/00365513.2018.1550806.Search in Google Scholar PubMed

13. Braga, F, Pasqualetti, S, Borrillo, F, Capoferri, A, Chibireva, M, Rovegno, L, et al.. Definition and application of performance specifications for measurement uncertainty of 23 common laboratory tests: linking theory to daily practice. Clin Chem Lab Med 2023;61:213–23. https://doi.org/10.1515/cclm-2022-0806.Search in Google Scholar PubMed

14. Zorbozan, N, Zorbozan, O. Reference change value and measurement uncertainty of CRP, ferritin, procalcitonin, troponin I and BNP tests in COVID-19 monitoring: how much change is significant? Int J Med Biochem 2021;4:150–6.10.14744/ijmb.2021.30602Search in Google Scholar

15. Borrillo, F, Panteghini, M. Current performance of C-reactive protein determination and derivation of quality specifications for its measurement uncertainty. Clin Chem Lab Med 2023;61:1552–7. https://doi.org/10.1515/cclm-2023-0069.Search in Google Scholar PubMed

16. Braga, F, Panteghini, M. Defining permissible limits for the combined uncertainty budget in the implementation of metrological traceability. Clin Biochem 2018;57:7–11. https://doi.org/10.1016/j.clinbiochem.2018.03.007.Search in Google Scholar PubMed

17. Panteghini, M, Braga, F, Camara, JE, Delatour, V, Van Uytfanghe, K, Vesper, HW, et al.. Optimizing available tools for achieving result standardization: value added by joint committee on traceability in laboratory medicine (JCTLM). Clin Chem 2021;67:1590–605. https://doi.org/10.1093/clinchem/hvab178.Search in Google Scholar PubMed

18. Denham, E, Mohn, B, Tucker, L, Lun, A, Cleave, P, Boswell, DR. Evaluation of immunoturbidimetric specific protein methods using the Architect ci8200: comparison with immunonephelometry. Ann Clin Biochem 2007;44:529–36. https://doi.org/10.1258/000456307782268237.Search in Google Scholar PubMed

19. Greipp, PR, San Miguel, J, Durie, BG, Crowley, JJ, Barlogie, B, Bladé, J, et al.. International staging system for multiple myeloma. J Clin Oncol 2005;23:3412–20. https://doi.org/10.1200/jco.2005.04.242.Search in Google Scholar

20. European Association for the Study of the Liver. EASL clinical practice guidelines: Wilson’s disease. J Hepatol 2012;56:671–85. https://doi.org/10.1016/j.jhep.2011.11.007.Search in Google Scholar PubMed

21. Fraser, CG. Reference change values. Clin Chem Lab Med 2012;50:807–12. https://doi.org/10.1515/cclm.2011.733.Search in Google Scholar PubMed

Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2025-0654).

Received: 2025-05-29
Accepted: 2025-08-11
Published Online: 2025-08-21
Published in Print: 2025-11-25

© 2025 Walter de Gruyter GmbH, Berlin/Boston

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Challenging the dogma: why reviewers should be allowed to use AI tools
  4. Multivariate approaches to improve the interpretation of laboratory data
  5. Review
  6. Interference of therapeutic monoclonal antibodies with electrophoresis and immunofixation of serum proteins: state of knowledge and systematic review
  7. Opinion Papers
  8. Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics
  9. The importance of laboratory medicine in the management of CKD-MBD: insights from the KDIGO 2023 controversies conference
  10. Supplementation of pyridoxal-5′-phosphate in aminotransferase reagents: a matter of patient safety
  11. HCV serology: an unfinished agenda
  12. From metabolic profiles to clinical interpretation: multivariate approaches to population-based and personalized reference intervals and reference change values
  13. Genetics and Molecular Diagnostics
  14. A multiplex allele specific PCR capillary electrophoresis (mASPCR-CE) assay for simultaneously analysis of SMN1/SMN2/NAIP copy number and SMN1 loss-of-function variants
  15. General Clinical Chemistry and Laboratory Medicine
  16. From assessment to action: experience from a quality improvement initiative integrating indicator evaluation and adverse event analysis in a clinical laboratory
  17. Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis
  18. Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications
  19. The current status of serum insulin measurements and the need for standardization
  20. Method comparison of plasma and CSF GFAP immunoassays across multiple platforms
  21. Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid
  22. Verification of the T50 Calciprotein Crystallization test: bias estimation and interferences
  23. An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference
  24. Oral salt loading combined with postural stimulation tests for confirming and subtyping primary aldosteronism
  25. Evaluating the performance of a multiparametric IgA assay for celiac disease diagnosis
  26. Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels
  27. Reference Values and Biological Variations
  28. Establishment of region-, age- and sex-specific reference intervals for aldosterone and renin with sandwich chemiluminescence immunoassays
  29. Validation of a plasma GFAP immunoassay and establishment of age-related reference values: bridging analytical performance and routine implementation
  30. Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study
  31. Hematology and Coagulation
  32. Evaluation of stability and potential interference on the α-thalassaemia early eluting peak and immunochromatographic strip test for α-thalassaemia --SEA carrier screening
  33. Cardiovascular Diseases
  34. Analytical and clinical evaluation of an automated high-sensitivity cardiac troponin I assay for whole blood
  35. Diabetes
  36. Method comparison of diabetes mellitus associated autoantibodies in serum specimens
  37. Letters to the Editor
  38. Permitting disclosed AI assistance in peer review: parity, confidentiality, and recognition
  39. Response to the editorial by Karl Lackner
  40. Hemolysis detection using the GEM 7000 at the point of care in a pediatric hospital setting: does it affect outcomes?
  41. Estimation of measurement uncertainty for free drug concentrations using ultrafiltration
  42. Cryoglobulin pre-analysis over the weekend
  43. Accelerating time from result to clinical action: impact of an automated critical results reporting system
  44. Recent decline in patient serum folate test levels using Roche Diagnostics Folate III assay
  45. Kidney stones consisting of 1-methyluric acid
  46. Congress Abstracts
  47. 7th EFLM Conference on Preanalytical Phase
  48. Association of Clinical Biochemists in Ireland Annual Conference
  49. Association of Clinical Biochemists in Ireland Annual Conference
  50. 17th Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
https://doi.org/10.1515/cclm-2025-0654
Keywords for this article
measurement uncertainty; immunoturbidimetry; serum proteins; ISO/TS 20914; analytical performance specifications; clinical laboratory quality

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Challenging the dogma: why reviewers should be allowed to use AI tools
  4. Multivariate approaches to improve the interpretation of laboratory data
  5. Review
  6. Interference of therapeutic monoclonal antibodies with electrophoresis and immunofixation of serum proteins: state of knowledge and systematic review
  7. Opinion Papers
  8. Urgent call to the European Commission to simplify and contextualize IVDR Article 5.5 for tailored and precision diagnostics
  9. The importance of laboratory medicine in the management of CKD-MBD: insights from the KDIGO 2023 controversies conference
  10. Supplementation of pyridoxal-5′-phosphate in aminotransferase reagents: a matter of patient safety
  11. HCV serology: an unfinished agenda
  12. From metabolic profiles to clinical interpretation: multivariate approaches to population-based and personalized reference intervals and reference change values
  13. Genetics and Molecular Diagnostics
  14. A multiplex allele specific PCR capillary electrophoresis (mASPCR-CE) assay for simultaneously analysis of SMN1/SMN2/NAIP copy number and SMN1 loss-of-function variants
  15. General Clinical Chemistry and Laboratory Medicine
  16. From assessment to action: experience from a quality improvement initiative integrating indicator evaluation and adverse event analysis in a clinical laboratory
  17. Evaluation of measurement uncertainty of 11 serum proteins measured by immunoturbidimetric methods according to ISO/TS 20914: a 1-year laboratory data analysis
  18. Assessing the harmonization of current total vitamin B12 measurement methods: relevance and implications
  19. The current status of serum insulin measurements and the need for standardization
  20. Method comparison of plasma and CSF GFAP immunoassays across multiple platforms
  21. Cerebrospinal fluid leptin in Alzheimer’s disease: relationship to plasma levels and to cerebrospinal amyloid
  22. Verification of the T50 Calciprotein Crystallization test: bias estimation and interferences
  23. An innovative immunoassay for accurate aldosterone quantification: overcoming low-level inaccuracy and renal dysfunction-associated interference
  24. Oral salt loading combined with postural stimulation tests for confirming and subtyping primary aldosteronism
  25. Evaluating the performance of a multiparametric IgA assay for celiac disease diagnosis
  26. Clinical significance of anti-mitochondrial antibodies and PBC-specific anti-nuclear antibodies in evaluating atypical primary biliary cholangitis with normal alkaline phosphatase levels
  27. Reference Values and Biological Variations
  28. Establishment of region-, age- and sex-specific reference intervals for aldosterone and renin with sandwich chemiluminescence immunoassays
  29. Validation of a plasma GFAP immunoassay and establishment of age-related reference values: bridging analytical performance and routine implementation
  30. Comparative analysis of population-based and personalized reference intervals for biochemical markers in peri-menopausal women: population from the PALM cohort study
  31. Hematology and Coagulation
  32. Evaluation of stability and potential interference on the α-thalassaemia early eluting peak and immunochromatographic strip test for α-thalassaemia --SEA carrier screening
  33. Cardiovascular Diseases
  34. Analytical and clinical evaluation of an automated high-sensitivity cardiac troponin I assay for whole blood
  35. Diabetes
  36. Method comparison of diabetes mellitus associated autoantibodies in serum specimens
  37. Letters to the Editor
  38. Permitting disclosed AI assistance in peer review: parity, confidentiality, and recognition
  39. Response to the editorial by Karl Lackner
  40. Hemolysis detection using the GEM 7000 at the point of care in a pediatric hospital setting: does it affect outcomes?
  41. Estimation of measurement uncertainty for free drug concentrations using ultrafiltration
  42. Cryoglobulin pre-analysis over the weekend
  43. Accelerating time from result to clinical action: impact of an automated critical results reporting system
  44. Recent decline in patient serum folate test levels using Roche Diagnostics Folate III assay
  45. Kidney stones consisting of 1-methyluric acid
  46. Congress Abstracts
  47. 7th EFLM Conference on Preanalytical Phase
  48. Association of Clinical Biochemists in Ireland Annual Conference
  49. Association of Clinical Biochemists in Ireland Annual Conference
  50. 17th Congress of the Portuguese Society of Clinical Chemistry, Genetics and Laboratory Medicine
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 29.12.2025 from https://www.degruyterbrill.com/document/doi/10.1515/cclm-2025-0654/html
Scroll to top button