Immune Netw.  2016 Dec;16(6):344-357. 10.4110/in.2016.16.6.344.

Reference Values for a Panel of Cytokinergic and Regulatory Lymphocyte Subpopulations

• Sorrenti V
• Marenda B
• Fortinguerra S
• Cecchetto
• Quartesan
• Zorzi G
• Zusso M
• Giusti P
• Buriani A

• KMID: 2362799
• DOI: http://doi.org/10.4110/in.2016.16.6.344

Abstract

Lymphocyte subpopulations producing cytokines and exerting regulatory functions represent key immune elements. Given their reciprocal interdependency lymphocyte subpopulations are usually assayed as diagnostic panels, rather than single biomarkers for specialist clinical use. This retrospective analysis on lymphocyte subpopulations, analyzed over the last few years in an outpatient laboratory in Northeast Italy, contributes to the establishment of reference values for several regulatory lymphocytes currently lacking such reference ranges for the general population. Mean values and ranges in a sample of Caucasian patients (mean age 42±8,5 years), were provided for Th1, Th2, Th17, Th-reg, Tc-reg, Tc-CD57⁺ and B1 lymphocytes. The results are consistent with what is found in literature for the single subtypes and are: Th1 157.8±60.3/µl (7.3%±2.9); Th2 118.2±52.2/µl (5.4%±2.5); Th17 221.6±90.2/µl (10.5%±4.4); Th-reg 15.1±10.2/µl (0.7%±0.4); Tc-reg 5.8±4.7/µl (0.3%±0.2); Tc-CD57+ 103.7±114.1/µl (4.6%±4.7); B1 33.7±22.8/µl (1.5%±0.9); (Values are mean±SD). The results show that despite their variability, mean values are rather consistent in all age or sex groups and can be used as laboratory internal reference for this regulatory panel. Adding regulatory cells to lymphocyte subpopulations panels allows a more complete view of the state of the subject's immune network balance, thus improving the personalization and the "actionability" of diagnostic data in a systems medicine perspective.

Keyword

Cytokines; Immune dysregulation; Lymphocyte subsets; Personalized medicine; Reference range; Diagnostic-omics

MeSH Terms

Biomarkers
Cytokines
Humans
Italy
Lymphocyte Subsets*
Lymphocytes*
Outpatients
Precision Medicine
Reference Values*
Retrospective Studies
Specialization
Systems Analysis
Biomarkers
Cytokines

Figure

• 

  Figure 1 Distribution of major peripheral blood leukocytes an lymphocyte subpopulations between sexes (A) and the two age ranges considered (above or below 40 yrs) (B). Box plots represent median with 25th and 75th percentile borders, error bars represent 10th and 90th percentile and outlier distribution with single dots. No significant differences between sexes and age were found.

• 

  Figure 2 Distribution of lymphocyte subpopulations for Gaussian analysis. Gaussian distribution of lymphocyte subpopulations: Th1, Th2, Th17 and Th-reg (A). Non-Gaussian distribution of lymphocytes subpopulations: Tc-CD57+, B1 cells, Tc-reg, Th-CD25+ and Tc-CD25+ (B).

• 

  Figure 3 Distribution of lymphocyte subpopulations between sexes (A) and the two age ranges considered (above or below 40 yrs) (B). Box plots represent median with 25th and 75th percentile borders. Error bars represent 10th and 90th percentile and outlier distribution with single dots. No differences between sexes and age were found.

• 

  Figure 4 A systems medicine view of the regulatory lymphocyte subpopulations panel. Activatory (A, green arrows) and Inhibitory (I, red lines) relationships between circulating cells were identified according to cellular or cytokinergic interactions previously described. In some cases different states of the same cell type produce conflicting stimuli and the relative relationship was thus not assigned in the figure. Th1 lymphocytes - A: Tc, Tc-CD57+, NK, MONO, NEUT; I: Th2, Th17, EOS (6970717273747576777879808182). Th2 lymphocytes – A: B lymphocytes, B1 lymphocytes, EOS, BASO, MONO; I: Th1, Th17 (77,7879838485868788). Th17 lymphocytes - A: Tc, B lymphocytes, NK, MONO, NEUT, EOS; I: Th1, Th-reg (738990919293949596109). Th-reg lymphocytes - I: Th1, Th2, Th17, Tc, NK, MONO, NEUT (56838892979899100101102). B lymphocytes - A: Th2, Th17; I: Th1, Th-reg, NK (103104105106). B1 lymphocytes - A: Th1, Th17 (107108). Tc-reg lymphocytes - I: Th1(42). NK cells - A: Tc, B cells, NEUT; I: Th2, Th-reg, EOS (767886899395110). MONO - A: Th2, B cells, BASO, NEUT, EOS (77106111112). NEUT - A: Th2, Th17, B cells, MONO, EOS, BASO; I:Th-reg (77789394113). Artwork was created with Microsoft Office PowerPoint 2007, standard blood cell cartoon symbolic representation was used.

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