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Test Code TREGS T-Cell Subsets, Regulatory (Tregs), Blood

Reporting Name

T Cell Subsets, Regulatory (Tregs)

Useful For

Evaluating patients with clinical features of IPEX (immune dysregulation, polyendocrinopathy, enteropathy, X-linked inheritance) and other primary immunodeficiencies, autoimmune diseases, allergy and asthma, and graft-vs-host disease post-hematopoietic stem cell transplantation

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Specimen Type

Whole Blood EDTA


Shipping Instructions


Testing performed Monday through Friday. Specimens not received by 4 p.m. Central time on Fridays may be canceled

 

Specimens arriving on the weekend and observed holidays may be canceled.

 

Collect and package specimen as close to shipping time as possible. It is recommended that specimens arrive within 24 hours of collection.



Necessary Information


The ordering healthcare professional's name and phone number are required.



Specimen Required


Container/Tube: Lavender top (EDTA)

Specimen Volume: 3 mL

Collection Instructions: Send whole blood specimen in original tube. Do not aliquot.

Additional Information: For serial monitoring, it is recommended that specimens are collected at the same time of day.


Specimen Minimum Volume

1 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Whole Blood EDTA Ambient 72 hours PURPLE OR PINK TOP/EDTA

Reference Values

The appropriate age-related reference values will be provided on the report.

Day(s) Performed

Monday through Friday

Test Classification

This test was developed using an analyte specific reagent. Its performance characteristics were determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

86359

86361

LOINC Code Information

Test ID Test Order Name Order LOINC Value
TREGS T Cell Subsets, Regulatory (Tregs) 90413-6

 

Result ID Test Result Name Result LOINC Value
609282 CD4 (T Cells) 24467-3
29143 % Activated CD4+ T cells (4+CD25+) 13332-2
29144 % Natural Tregs 89320-6
29145 % N. Naive Tregs 89319-8
29146 % CD4+CD25-CD127+ (Tr1/Th3) 89318-0
29147 Activated CD4+ T cells (4+CD25+) 26982-9
29148 CD4+CD25+CD127loCD45RO+ (Nat Tregs) 89316-4
29149 CD4+CD25+CD127loCD45RA+ Naive Tregs 89315-6
29150 CD4+CD25-CD127+ (Tr1/Th3) 89317-2
29177 Interpretation 69052-9

Interpretation

The lack of regulatory T cells (Tregs) is associated with variants in the FOXP3 gene. Low Tregs are also seen in the context of other inborn errors of immunity. Reduced Nn Tregs and natural Tregs are likely to predispose to autoimmunity, while reductions in Th3/Tr1 cells may impair oral and peripheral tolerance, also facilitating the development of autoimmunity.

 

The presence of expanded naive Tregs may indicate a process of malignant transformation, if other clinical features of malignant disease are present.

 

Increased Tregs in donor stem cell allografts have been associated with a reduced incidence of graft-versus-host disease (ie, mediating a protective effect) after allogeneic stem cell transplantation.

Clinical Reference

1. Sakaguchi S, Sakaguchi N, Shimizu J, et al. Immunologic tolerance maintained by CD25+CD4+ regulatory T cells: their common role in controlling autoimmunity, tumor immunity, and transplantation tolerance. Immunol Rev. 2001;182:18-32

2. Liu W, Putnam AL, Xu-Yu Z, et al. CD127 expression inversely correlates with FOXP3 and suppressive function of human CD4+ Treg cells. J Exp Med. 2006;203(7):1701-1711

3. Seddiki N, Santner-Nanan B, Tangye SG, et al. Persistence of naive CD45RA+ regulatory T-cells in adult life. Blood. 2006;107(7):2830-2838

4. Seddiki N, Santner-Nanan B, Martinson J, et al. Expression of interleukin (IL)-2 and IL-7 receptors discriminates between human regulatory and activated T-cells. J Exp Med. 2006;203(7):1693-1700

5. Valmori D, Merlo A, Souleimanian NE, Hesdorffer CS, Ayyoub M. A peripheral circulating compartment of natural naive CD4 Tregs. J Clin Invest. 2005;115(7):1953-1962

6. Torgerson TR, Ochs HD. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked: forkhead box protein 3 mutations and lack of regulatory T-cells. J Allergy Clin Immunol. 2007;120(4):744-750

7. Wobma H, Janssen E. Expanding IPEX: Inborn errors of regulatory T cells. Rheum Dis Clin North Am. 2023;49(4):825-840. doi:10.1016/j.rdc.2023.06.0098. Beyer M, Kochanek M, Giese T, et al. In vivo peripheral expansion of naive CD4+CD25high FOXP3 + regulatory T cells in patients with multiple myeloma. Blood. 2006;107(10):3940-3949

9. Carmichael KF, Abayomi A. Analysis of diurnal variation of lymphocyte subsets in healthy subjects and its implication in HIV monitoring and treatment. 15th Intl Conference on AIDS, Bangkok, Thailand, 2004, Abstract B11052

10. Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T. Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood. 2009;113(21):5134-5143

11. Dimitrov S, Lange T, Nohroudi K, Born J. Number and function of circulating human antigen presenting cells regulated by sleep. Sleep. 2007;30(4):401-411

12. Kronfol Z, Nair M, Zhang Q, Hill EE, Brown MB. Circadian immune measures in healthy volunteers: relationship to hypothalamic-pituitary-adrenal axis hormones and sympathetic neurotransmitters. Psychosom Med. 1997;59(1):42-50

13. Malone JL, Simms TE, Gray GC, Wagner KF, Burge JR, Burke DS. Sources of variability in repeated T-helper lymphocyte counts from human immunodeficiency virus type 1-infected patients: total lymphocyte count fluctuations and diurnal cycle are important. J Acquir Immune Defic Syndr (1988). 1990;3(2):144-151

14. Paglieroni TG, Holland PV. Circannual variation in lymphocyte subsets, revisited. Transfusion. 1994;34(6):512-516

15. Gambineri E, Ciullini Mannurita S, Hagin D, et al. Clinical, immunological, and molecular heterogeneity of 173 patients with the phenotype of immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome. Front Immunol. 2018;9:2411

16. Park JH, Lee KH, Jeon B, et al. Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome: A systematic review. Autoimmun Rev. 2020;19(6):102526

17. Delmonte OM, Fleisher TA. Flow cytometry: Surface markers and beyond. J Allergy Clin Immunol. 2019;143(2):528-537

18. Knight V, Heimall JR, Chong H, et al. A toolkit and framework for optimal laboratory evaluation of individuals with suspected primary immunodeficiency. J Allergy Clin Immunol Pract. 2021;9(9):3293-3307.e6

Report Available

3 to 4 days

Method Name

Flow Cytometry