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Within- and between-subject biological variation estimates for the enumeration of lymphocyte deep immunophenotyping and monocyte subsets

  • Kai Guo ORCID logo , Xiaoran Feng , Lei Xu , Chenbin Li ORCID logo , Yating Ma and Mingting Peng EMAIL logo
Published/Copyright: May 31, 2024

Abstract

Objectives

This study aimed to deliver biological variation (BV) estimates for 25 types of lymphocyte subpopulations subjected to deep immunophenotyping (memory T/B cells, regulatory T cells, etc.) and classical, intermediate, and nonclassical monocyte subsets based on the full spectrum flow cytometry (FS-FCM) and a Biological Variation Data Critical Appraisal Checklist (BIVAC) design.

Methods

Samples were collected biweekly from 60 healthy Chinese adults over 10 consecutive two-week periods. Each sample was measured in duplicate within a single run for lymphocyte deep immunophenotyping and monocyte subset determination using FS-FCM, including the percentage (%) and absolute count (cells/μL). After trend adjustment, a Bayesian model was applied to deliver the within-subject BV (CVI) and between-subject BV (CVG) estimates with 95 % credibility intervals.

Results

Enumeration (% and cells/μL) for 25 types of lymphocyte deep immunophenotyping and three types of monocyte subset percentages showed considerable variability in terms of CVI and CVG. CVI ranged from 4.23 to 47.47 %. Additionally, CVG ranged between 10.32 and 101.30 %, except for CD4+ effector memory T cells re-expressing CD45RA. No significant differences were found between males and females for CVI and CVG estimates. Nevertheless, the CVGs of PD-1+ T cells (%) may be higher in females than males. Based on the desired analytical performance specification, the maximum allowable imprecision immune parameter was the CD8+PD-1+ T cell (cells/μL), with 23.7 %.

Conclusions

This is the first study delivering BV estimates for 25 types of lymphocyte subpopulations subjected to deep immunophenotyping, along with classical, intermediate, and nonclassical monocyte subsets, using FS-FCM and adhering to the BIVAC design.


Corresponding author: Prof. Mingting Peng, National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, Beijing 100730, P.R. China; and National Center for Clinical Laboratories, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, P.R. China, E-mail:

Funding source: National Special Project for Science and Technology Basic Work of Ministry of Science and Technology of China

Award Identifier / Grant number: 2013FY113800

Funding source: Discipline Construction Project of Peking Union Medical College

Award Identifier / Grant number: No. 201920102202

Funding source: National High Level Hospital Clinical Research Funding of China

Award Identifier / Grant number: BJ-2022-139

Acknowledgments

We are grateful to all the volunteers and colleagues participating in the BV study. The authors thank Mrs. Hong Lu, Dr. Zhongli Du, Dr. Gaofeng Hu, and Dr. Chengshan Xu from the National Center for Clinical Laboratories, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing Hospital/National Center of Gerontology, China, for all their invaluable efforts and help. We also thank Thomas Røraas and their team for their invaluable contribution to statistical methods and data analysis.

  1. Research ethics: The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The Ethics Committee of Beijing Hospital gave expedited approval to this study involved human samples. The authors have no other ethical conflicts to disclose.

  2. Informed consent: Informed consent was obtained from all individuals included in this study.

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

  4. Competing interests: The authors state no conflict of interest.

  5. Research funding: This study was supported by the grant from National HighLevel Hospital Clinical Research Funding of China (BJ-2022-139), the Discipline Construction Project of Peking Union Medical College (No. 201920102202), and the National Special Project for Science and Technology Basic Work of Ministry of Science and Technology of China (2013FY113800).

  6. Data availability: The raw data can be obtained on request from the corresponding author.

References

1. Panteghini, M, Sandberg, S. Defining analytical performance specifications 15 years after the Stockholm conference. Clin Chem Lab Med 2015;53:829–32. https://doi.org/10.1515/cclm-2015-0303.Search in Google Scholar PubMed

2. Faser, CG. Biological variation: from principles to practice. Washington DC: AACC Press; 2001:2–13 pp.Search in Google Scholar

3. 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

4. Coşkun, A, Sandberg, S, Unsal, I, Cavusoglu, C, Serteser, M, Kilercik, M, et al.. Personalized reference intervals in laboratory medicine: a new model based on within-subject biological variation. Clin Chem 2021;67:374–84. https://doi.org/10.1093/clinchem/hvaa233.Search in Google Scholar PubMed

5. Johnson, PR, Shahangian, S, Astles, JR. Managing biological variation data: modern approaches for study design and clinical application. Crit Rev Clin Lab Sci 2021;58:493–512. https://doi.org/10.1080/10408363.2021.1932718.Search in Google Scholar PubMed

6. Kumar, BV, Connors, TJ, Farber, DL. Human T cell development, localization, and function throughout life. Immunity 2018;48:202–13. https://doi.org/10.1016/j.immuni.2018.01.007.Search in Google Scholar PubMed PubMed Central

7. Patel, AA, Zhang, Y, Fullerton, JN, Boelen, L, Rongvaux, A, Maini, AA, et al.. The fate and lifespan of human monocyte subsets in steady state and systemic inflammation. J Exp Med 2017;214:1913–23. https://doi.org/10.1084/jem.20170355.Search in Google Scholar PubMed PubMed Central

8. Laboratory Medicine Committee of Chinese Association of Integrative Medicine. The consensus of Chinese experts on refined analysis of immune cell subsets in peripheral blood by multi-parameter flow cytometry. Chin J Prev Med 2023;57:1729–47. https://doi.org/10.3760/cma.j.cn112150-20230721-00021. Chinese.Search in Google Scholar PubMed

9. Laboratory Medicine Society of Chinese Medical Association, Laboratory Medicine Specialist (Technician) Branch of Beijing Medical Doctor Association, National Cancer Center, National Cancer Regional Medical Center, National Clinical Research Center of Laboratory Medicine (the First Hospital of China Medical University). Chinese expert consensus on laboratory detection of peripheral blood cellular immune function in solid tumors. Chin J Lab Med 2023;46:1235–48. Chinese.Search in Google Scholar

10. National Clinical Research Center for Laboratory Medicine (the First Hospital of China Medical University), Chinese Society of Laboratory Medicine, National Center for Clinical Laboratories, Editorial Board of Chinese Society of Laboratory Medicine. Consensus on the clinical application of flow cytometry. Chin J Lab Med 2023;46:792–801. Chinese.Search in Google Scholar

11. Professional Committee of Medical Laboratory Quality Management of China Quality Association for Pharmaceuticals. Consensus of experts on the application of lymphocyte subsets in hematologic malignancies. Int J Lab Med 2023;44:1793–802. Chinese.Search in Google Scholar

12. Aarsand, AK, Røraas, T, Fernandez-Calle, P, Ricos, C, Díaz-Garzón, J, Jonker, N, et al.. The biological variation data critical appraisal checklist: a standard for evaluating studies on biological variation. Clin Chem 2018;64:501–14. https://doi.org/10.1373/clinchem.2017.281808.Search in Google Scholar PubMed

13. Falay, M, Senes, M, Korkmaz, S, Zararsız, G, Turhan, T, Okay, M, et al.. Biological variation of peripheral blood T-lymphocytes. J Immunol Methods 2019;470:1–5. https://doi.org/10.1016/j.jim.2019.04.002.Search in Google Scholar PubMed

14. Aziz, N, Detels, R, Quint, JJ, Gjertson, D, Ryner, T, Butch, AW. Biological variation of immunological blood biomarkers in healthy individuals and quality goals for biomarker tests. BMC Immunol 2019;20:33. https://doi.org/10.1186/s12865-019-0313-0.Search in Google Scholar PubMed PubMed Central

15. Huang, C, Li, W, Wu, W, Chen, Q, Guo, Y, Zhang, Y, et al.. Intra-day and inter-day biological variations of peripheral blood lymphocytes. Clin Chim Acta 2015;438:166–70. https://doi.org/10.1016/j.cca.2014.08.009.Search in Google Scholar PubMed

16. Tosato, F, Bernardi, D, Sanzari, MC, Pantano, G, Plebani, M. Biological variability of lymphocyte subsets of human adults’ blood. Clin Chim Acta 2013;424:159–63. https://doi.org/10.1016/j.cca.2013.06.001.Search in Google Scholar PubMed

17. Kanodia, P, Kaur, G, Coshic, P, Chatterjee, K, Neeman, T, George, A, et al.. Characterization of biological variation of peripheral blood immune cytome in an Indian cohort. Sci Rep 2019;9:14735. https://doi.org/10.1038/s41598-019-51294-7.Search in Google Scholar PubMed PubMed Central

18. Flores-Gonzalez, J, Cancino-Díaz, JC, Chavez-Galan, L. Flow cytometry: from experimental design to its application in the diagnosis and monitoring of respiratory diseases. Int J Mol Sci 2020;21. https://doi.org/10.3390/ijms21228830.Search in Google Scholar PubMed PubMed Central

19. Nolan, JP. The evolution of spectral flow cytometry. Cytometry A 2022;101:812–7. https://doi.org/10.1002/cyto.a.24566.Search in Google Scholar PubMed

20. Park, LM, Lannigan, J, Jaimes, MC. OMIP-069: forty-color full spectrum flow cytometry panel for deep immunophenotyping of major cell subsets in human peripheral blood. Cytometry A 2020;97:1044–51. https://doi.org/10.1002/cyto.a.24213.Search in Google Scholar PubMed PubMed Central

21. Brestoff, JR. Full spectrum flow cytometry in the clinical laboratory. Int J Lab Hematol 2023;45:44–9. https://doi.org/10.1111/ijlh.14098.Search in Google Scholar PubMed PubMed Central

22. CLSI. Defining, establishing, and verifying reference intervals in the clinical laboratory; approved guideline third edition. CLSI document EP28-A3c. Wayne, PA: Clinical and Laboratory Standards Institute; 2008.Search in Google Scholar

23. Carobene, A, Strollo, M, Jonker, N, Barla, G, Bartlett, WA, Sandberg, S, et al.. Sample collections from healthy volunteers for biological variation estimates’ update: a new project undertaken by the Working Group on Biological Variation established by the European Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2016;54:1599–608. https://doi.org/10.1515/cclm-2016-0035.Search in Google Scholar PubMed

24. Fraser, CG, Harris, EK. Generation and application of data on biological variation in clinical chemistry. Crit Rev Clin Lab Sci 1989;27:409–37. https://doi.org/10.3109/10408368909106595.Search in Google Scholar PubMed

25. CLSI. Validation of assays performed by flow cytometry. 1st ed. CLSI guideline H62. Wayne, PA:Clinical and Laboratory Standards Institute; 2021.Search in Google Scholar

26. Oras, A, Quirant-Sanchez, B, Popadic, D, Thunberg, S, Winqvist, O, Heck, S, et al.. Comprehensive flow cytometric reference intervals of leukocyte subsets from six study centers across Europe. Clin Exp Immunol 2020;202:363–78. https://doi.org/10.1111/cei.13491.Search in Google Scholar PubMed PubMed Central

27. Aarsand, AK, Kristoffersen, AH, Sandberg, S, Støve, B, Coşkun, A, Fernandez-Calle, P, et al.. The European Biological Variation Study (EuBIVAS): biological variation data for coagulation markers estimated by a Bayesian model. Clin Chem 2021;67:1259–70. https://doi.org/10.1093/clinchem/hvab100.Search in Google Scholar PubMed

28. Røraas, T, Sandberg, S, Aarsand, AK, Støve, B. A Bayesian approach to biological variation analysis. Clin Chem 2019;65:995–1005. https://doi.org/10.1373/clinchem.2018.300145.Search in Google Scholar PubMed

29. Harris, EK, Brown, SS. Temporal changes in the concentrations of serum constituents in healthy men. Distributions of within-person variances and their relevance to the interpretation of differences between successive measurements. Ann Clin Biochem 1979;16:169–76. https://doi.org/10.1177/000456327901600142.Search in Google Scholar PubMed

30. Burdick, RK, Graybill, FA. Confidence intervals on variance components. Boca Raton, FL:CRC Press; 1992.10.1201/9781482277142Search in Google Scholar

31. Harris, EK. Effects of intra-and interindividual variation on the appropriate use of normal ranges. Clin Chem 1974;20:1535–42. https://doi.org/10.1093/clinchem/20.12.1535.Search in Google Scholar

32. Dot, D, Miró, J, Fuentes-Arderiu, X. Within-subject biological variation of hematological quantities and analytical goals. Arch Pathol Lab Med 1992;116:825–6.Search in Google Scholar

33. Selliah, N, Nash, V, Eck, S, Green, C, Oldaker, T, Stewart, J, et al.. Flow cytometry method validation protocols. Curr Protoc 2023;3:e868. https://doi.org/10.1002/cpz1.868.Search in Google Scholar PubMed

34. Selliah, N, Eck, S, Green, C, Oldaker, T, Stewart, J, Vitaliti, A, et al.. Flow cytometry method validation protocols. Curr Protoc 2019;87:e53. https://doi.org/10.1002/cpcy.53.Search in Google Scholar PubMed

35. Røraas, T, Petersen, PH, Sandberg, S. Confidence intervals and power calculations for within-person biological variation: effect of analytical imprecision, number of replicates, number of samples, and number of individuals. Clin Chem 2012;58:1306–13. https://doi.org/10.1373/clinchem.2012.187781.Search in Google Scholar PubMed

36. Braga, F, Panteghini, M. Generation of data on within-subject biological variation in laboratory medicine: an update. Crit Rev Clin Lab Sci 2016;53:313–25. https://doi.org/10.3109/10408363.2016.1150252.Search in Google Scholar PubMed

37. Harris, EK, Kanofsky, P, Shakarji, G, Cotlove, E. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects: II. Estimating biological components of variation. Clin Chem 1970;16:1022–7. https://doi.org/10.1093/clinchem/16.12.1022.Search in Google Scholar

38. Cotlove, E, Harris, EK, Williams, GZ. Biological and analytic components of variation in long-term studies of serum constituents in normal subjects: III. Physiological and medical implications. Clin Chem 1970;16:1028–32. https://doi.org/10.1093/clinchem/16.12.1028.Search in Google Scholar

39. Braga, F, Ferraro, S, Lanzoni, M, Szöke, D, Panteghini, M. Estimate of intraindividual variability of C-reactive protein: a challenging issue. Clin Chim Acta 2013;419:85–6. https://doi.org/10.1016/j.cca.2013.02.004.Search in Google Scholar PubMed

40. Rotterdam, EP, Katan, MB, Knuiman, JT. Importance of time interval between repeated measurements of total or high-density lipoprotein cholesterol when estimating an individual’s baseline concentrations. Clin Chem 1987;33:1913–5. https://doi.org/10.1093/clinchem/33.10.1913.Search in Google Scholar

41. Røys, EÅ, Guldhaug, NA, Viste, K, Jones, GD, Alaour, B, Sylte, MS, et al.. Sex hormones and adrenal steroids: biological variation estimated using direct and indirect methods. Clin Chem 2023;69:100–9. https://doi.org/10.1093/clinchem/hvac175.Search in Google Scholar PubMed

42. Ferrer‐Font, L, Small, SJ, Lewer, B, Pilkington, KR, Johnston, LK, Park, LM, et al.. Panel optimization for high-dimensional immunophenotyping assays using full-spectrum flow cytometry. Curr Protoc 2021;1:e222. https://doi.org/10.1002/cpz1.222.Search in Google Scholar PubMed

43. Farrand, K, Holz, LE, Ferrer-Font, L, Wilson, MD, Ganley, M, Minnell, JJ, et al.. Using full-spectrum flow cytometry to phenotype memory T and NKT cell subsets with optimized tissue-specific preparation protocols. Curr Protoc 2022;2:e482. https://doi.org/10.1002/cpz1.482.Search in Google Scholar PubMed

44. Kalina, T, Flores-Montero, J, van der Velden, VHJ, Martin-Ayuso, M, Böttcher, S, Ritgen, M, et al.. EuroFlow standardization of flow cytometer instrument settings and immunophenotyping protocols. Leukemia 2012;26:1986–2010. https://doi.org/10.1038/leu.2012.122.Search in Google Scholar PubMed PubMed Central

45. CLSI. Enumeration of immunologically defined cell populations by flow cytometry; approved guideline second edition. CLSI document H42-A2. Wayne, PA: Clinical and Laboratory Standards Institute; 2007.Search in Google Scholar

46. Whitby, L, Whitby, A, Fletcher, M, Helbert, M, Reilly, JT, Barnett, D. Comparison of methodological data measurement limits in CD4+ T lymphocyte flow cytometric enumeration and their clinical impact on HIV management. Cytometry B Clin Cytom 2013;84B:248–54. https://doi.org/10.1002/cyto.b.21094.Search in Google Scholar PubMed

47. Mandy, FF, Nicholson, JK, McDougal, JS, CDC. Guidelines for performing single-platform absolute CD4+ T-cell determinations with CD45 gating for persons infected with human immunodeficiency virus. Centers for Disease Control and Prevention. MMWR Recomm Rep 2003;52:1–13.Search in Google Scholar

48. Whitby, L, Whitby, A, Fletcher, M, Barnett, D. Current laboratory practices in flow cytometry for the enumeration of CD 4+T-lymphocyte subsets. Cytometry B Clin Cytom 2015;88:305–11. https://doi.org/10.1002/cyto.b.21241.Search in Google Scholar PubMed

49. Grossi, V, Infantino, M, Meacci, F, Bellio, E, Bellio, V, Ciotta, G, et al.. Comparison of methods and TAT assessment: volumetric AQUIOS CL and bead-based FACS CANTO II cytometers. Cytometry B Clin Cytom 2017;94:674–8. https://doi.org/10.1002/cyto.b.21513.Search in Google Scholar PubMed

50. Ward, RY, Stevens, M, Bashir, S. Metrological traceability in flow cytometry? Evaluation of a new volumetric method for lymphocyte subsets. Int J Lab Hematol 2024;46:488–94. https://doi.org/10.1111/ijlh.14219.Search in Google Scholar PubMed

51. Sommer, U, Eck, S, Marszalek, L, Stewart, JJ, Bradford, J, McCloskey, TW, et al.. High-sensitivity flow cytometric assays: considerations for design control and analytical validation for identification of Rare events. Cytometry B Clin Cytom 2020;100:42–51. https://doi.org/10.1002/cyto.b.21949.Search in Google Scholar PubMed

52. Valle, A, Maugeri, N, Manfredi, AA, Battaglia, M. Standardization in flow cytometry: correct sample handling as a priority. Nat Rev Immunol 2012;12:864. https://doi.org/10.1038/nri3158-c3.Search in Google Scholar PubMed

53. Brodin, P, Duffy, D, Quintana-Murci, L. A call for blood – in human immunology. Immunity 2019;50:1335–6. https://doi.org/10.1016/j.immuni.2019.05.012.Search in Google Scholar PubMed

54. Le Lann, L, Jouve, P-E, Alarcón-Riquelme, M, Jamin, C, Pers, J-O, Alvarez, M, et al.. Standardization procedure for flow cytometry data harmonization in prospective multicenter studies. Sci Rep 2020;10:11567. https://doi.org/10.1038/s41598-020-68468-3.Search in Google Scholar PubMed PubMed Central

55. Liu, W, Putnam, AL, Xu-yu, Z, Szot, GL, Lee, MR, Zhu, S, et al.. CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells. J Exp Med 2006;203:1701–11. https://doi.org/10.1084/jem.20060772.Search in Google Scholar PubMed PubMed Central

56. Lacher, DA, Barletta, J, Hughes, JP. Biological variation of hematology tests based on the 1999–2002 National Health and Nutrition Examination Survey. Natl Health Stat Report 2012:1–10.Search in Google Scholar

57. Lacher, DA, Hughes, JP, Carroll, MD. Biological variation of laboratory analytes based on the 1999–2002 National Health and Nutrition Examination Survey. Natl Health Stat Report 2010:1–7.Search in Google Scholar

58. Miller, WG, Horowitz, GL, Ceriotti, F, Fleming, JK, Greenberg, N, Katayev, A, et al.. Reference intervals: strengths, weaknesses, and challenges. Clin Chem 2016;62:916–23. https://doi.org/10.1373/clinchem.2016.256511.Search in Google Scholar PubMed

59. Aziz, N, Jamieson, BD, Quint, JJ, Martinez-Maza, O, Chow, M, Detels, R. Longitudinal intra- and inter-individual variation in T-cell subsets of HIV-infected and uninfected men participating in the LA multi-center AIDS cohort study. Medicine 2019;98:e17525. https://doi.org/10.1097/md.0000000000017525.Search in Google Scholar

60. Beam, CA, Beli, E, Wasserfall, CH, Woerner, SE, Legge, MT, Evans-Molina, C, et al.. Peripheral immune circadian variation, synchronisation and possible dysrhythmia in established type 1 diabetes. Diabetologia 2021;64:1822–33. https://doi.org/10.1007/s00125-021-05468-6.Search in Google Scholar PubMed PubMed Central


Supplementary Material

This article contains supplementary material (https://doi.org/10.1515/cclm-2024-0371).


Received: 2024-03-21
Accepted: 2024-05-05
Published Online: 2024-05-31
Published in Print: 2024-10-28

© 2024 Walter de Gruyter GmbH, Berlin/Boston

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