Thymic and Bone Marrow Output in Patients with Common Variable Immunodeficiency

Overview

Journal J Clin Immunol

Publisher Springer

Specialty Allergy & Immunology

Date 2011 Apr 15

PMID 21491094

Citations 20

Authors

Federico Serana

Paolo Airo

Marco Chiarini

Cinzia Zanotti

Mirko Scarsi

Micol Frassi

Vassilios Lougaris

Alessandro Plebani

Luigi Caimi

Luisa Imberti

Affiliations

Soon will be listed here.

Abstract

Objective: The study aims to obtain more information about the immune deficit of common variable immunodeficiency (CVID) patients.

Materials And Methods: A new real-time PCR assay was used to quantify T and B lymphocyte mobilization from the production and maturation sites through the detection of T cell receptor excision circles (TRECs) and kappa-deleting recombination circles (KRECs) and to allow the estimation of the average number of B cell divisions. T and B lymphocyte subsets were analyzed by flow cytometry.

Results: The number of TREC(+) lymphocytes, which depends on age and gender, was significantly reduced in CVID patients. Similarly, KREC concentration was lower than in controls. Classification of patients according to the percentage of memory switched B cells showed that patients belonging to MB2 group and therefore with conserved B cell maturation have the lowest new B cell output but increased average peripheral divisions, leading to the highest B cell number.

Conclusions: TREC and KREC quantification can be helpful for a more complete and informative understanding of a heterogeneous disease such as CVID.

Citing Articles

Can T-cell and B-cell excision circles predict development of inhibitors in pediatric hemophilia A?.

Levy-Mendelovich S, Lev A, Avishai E, Budnik I, Dardik R, Barg A Pediatr Res. 2022; 93(6):1546-1550.

PMID: 36045224 DOI: 10.1038/s41390-022-02268-5.

Lymphocyte Subgroups and KREC Numbers in Common Variable Immunodeficiency: A Single Center Study.

Yaz I, Ozbek B, Ng Y, Cetinkaya P, Oskay Halacli S, Tan C J Clin Immunol. 2020; 40(3):494-502.

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The ESC: The Dangerous By-Product of V(D)J Recombination.

Smith A, Scott J, Boyes J Front Immunol. 2019; 10:1572.

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Differentiation of Common Variable Immunodeficiency From IgG Deficiency.

Filion C, Taylor-Black S, Maglione P, Radigan L, Cunningham-Rundles C J Allergy Clin Immunol Pract. 2018; 7(4):1277-1284.

PMID: 30557717 PMC: 6519441. DOI: 10.1016/j.jaip.2018.12.004.

Thymopoiesis in Pre- and Post-Hematopoietic Stem Cell Transplantation.

da Rocha L, de Barros S, Bandeira F, Bollini A, Testa L, Simione A Front Immunol. 2018; 9:1889.

PMID: 30245685 PMC: 6137257. DOI: 10.3389/fimmu.2018.01889.

References

Douek D, Betts M, Hill B, Little S, Lempicki R, Metcalf J . Evidence for increased T cell turnover and decreased thymic output in HIV infection. J Immunol. 2001; 167(11):6663-8. DOI: 10.4049/jimmunol.167.11.6663. View

Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E . The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2007; 111(1):77-85. DOI: 10.1182/blood-2007-06-091744. View

De Vera M, Al-Harthi L, Gewurz A . Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles. Ann Allergy Asthma Immunol. 2004; 93(5):478-84. DOI: 10.1016/S1081-1206(10)61416-0. View

Maurer D, Fischer G, Fae I, Majdic O, Stuhlmeier K, von Jeney N . IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset. J Immunol. 1992; 148(12):3700-5. View

Moratto D, Gulino A, Fontana S, Mori L, Pirovano S, Soresina A . Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients. Clin Immunol. 2006; 121(2):203-14. DOI: 10.1016/j.clim.2006.07.003. View

Farrant J, Spickett G, Matamoros N, Copas D, Hernandez M, North M . Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID). Immunodeficiency. 1994; 5(2):159-69. View

Goldacker S, Warnatz K . Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol. 2005; 5(6):504-9. DOI: 10.1097/01.all.0000191888.97397.b3. View

Agematsu K, Nagumo H, Yang F, Nakazawa T, Fukushima K, Ito S . B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol. 1997; 27(8):2073-9. DOI: 10.1002/eji.1830270835. View

Jacquot S, Paris E, Kobata T, Tanaka Y, Morimoto C, Schlossman S . B cell co-receptors regulating T cell-dependent antibody production in common variable immunodeficiency: CD27 pathway defects identify subsets of severely immuno-compromised patients. Int Immunol. 2001; 13(7):871-6. DOI: 10.1093/intimm/13.7.871. View

10.

Stagg A, Funauchi M, Knight S, Webster A, Farrant J . Failure in antigen responses by T cells from patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 1994; 96(1):48-53. PMC: 1534526. DOI: 10.1111/j.1365-2249.1994.tb06228.x. View

11.

Bryant A, Calver N, Toubi E, Webster A, Farrant J . Classification of patients with common variable immunodeficiency by B cell secretion of IgM and IgG in response to anti-IgM and interleukin-2. Clin Immunol Immunopathol. 1990; 56(2):239-48. DOI: 10.1016/0090-1229(90)90145-g. View

12.

Fronkova E, Muzikova K, Mejstrikova E, Kovac M, Formankova R, Sedlacek P . B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL. Bone Marrow Transplant. 2008; 42(3):187-96. DOI: 10.1038/bmt.2008.122. View

13.

Vlkova M, Thon V, Sarfyova M, Blaha L, Svobodnik A, Lokaj J . Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006; 143(2):373-9. PMC: 1809591. DOI: 10.1111/j.1365-2249.2006.02999.x. View

14.

Sottini A, Ghidini C, Zanotti C, Chiarini M, Caimi L, Lanfranchi A . Simultaneous quantification of recent thymic T-cell and bone marrow B-cell emigrants in patients with primary immunodeficiency undergone to stem cell transplantation. Clin Immunol. 2010; 136(2):217-27. DOI: 10.1016/j.clim.2010.04.005. View

15.

Mouillot G, Carmagnat M, Gerard L, Garnier J, Fieschi C, Vince N . B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010; 30(5):746-55. DOI: 10.1007/s10875-010-9424-3. View

16.

Banchereau J, Rousset F . Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol. 1992; 52:125-262. DOI: 10.1016/s0065-2776(08)60876-7. View

17.

Brouet J, Chedeville A, Fermand J, Royer B . Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol. 2000; 30(9):2516-20. DOI: 10.1002/1521-4141(200009)30:9<2516::AID-IMMU2516>3.0.CO;2-Z. View

18.

Motta M, Chiarini M, Ghidini C, Zanotti C, Lamorgese C, Caimi L . Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients. J Transl Med. 2010; 8:111. PMC: 2991330. DOI: 10.1186/1479-5876-8-111. View

19.

Chen X, Barfield R, Benaim E, Leung W, Knowles J, Lawrence D . Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients. Blood. 2004; 105(2):886-93. DOI: 10.1182/blood-2004-04-1405. View

20.

Losi C, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S . Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol. 2005; 25(5):496-502. DOI: 10.1007/s10875-005-5637-2. View