Skip to main content
Erschienen in: Journal of Clinical Immunology 4/2011

01.08.2011

Thymic and Bone Marrow Output in Patients with Common Variable Immunodeficiency

verfasst von: Federico Serana, Paolo Airò, Marco Chiarini, Cinzia Zanotti, Mirko Scarsi, Micol Frassi, Vassilios Lougaris, Alessandro Plebani, Luigi Caimi, Luisa Imberti

Erschienen in: Journal of Clinical Immunology | Ausgabe 4/2011

Einloggen, um Zugang zu erhalten

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.
Anhänge
Nur mit Berechtigung zugänglich
Literatur
1.
Zurück zum Zitat Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48.PubMedCrossRef Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34–48.PubMedCrossRef
2.
Zurück zum Zitat Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93:190–7.PubMedCrossRef Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999;93:190–7.PubMedCrossRef
3.
Zurück zum Zitat Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R, et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003;4:261–8.PubMedCrossRef Grimbacher B, Hutloff A, Schlesier M, Glocker E, Warnatz K, Drager R, et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003;4:261–8.PubMedCrossRef
4.
Zurück zum Zitat Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34.PubMedCrossRef Castigli E, Wilson SA, Garibyan L, Rachid R, Bonilla F, Schneider L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829–34.PubMedCrossRef
5.
Zurück zum Zitat Losi CG, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S, et al. Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol. 2005;25:496–502.PubMedCrossRef Losi CG, Silini A, Fiorini C, Soresina A, Meini A, Ferrari S, et al. Mutational analysis of human BAFF receptor TNFRSF13C (BAFF-R) in patients with common variable immunodeficiency. J Clin Immunol. 2005;25:496–502.PubMedCrossRef
6.
Zurück zum Zitat Salzer U, Chapel HM, Webster AD, Pan-Hammarström Q, Schmitt-Graeff A, Schlesier M, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820–8.PubMedCrossRef Salzer U, Chapel HM, Webster AD, Pan-Hammarström Q, Schmitt-Graeff A, Schlesier M, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820–8.PubMedCrossRef
7.
Zurück zum Zitat van Zelm MC, Reisli I, van der Burg M, Castano D, van Noesel CJ, van Tol MJ, et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006;354:1901–12.PubMedCrossRef van Zelm MC, Reisli I, van der Burg M, Castano D, van Noesel CJ, van Tol MJ, et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006;354:1901–12.PubMedCrossRef
8.
Zurück zum Zitat Vorechovsky I, Zetterquist H, Paganelli R, Koskinen S, Webster AD, Bjorkander J, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. 1995;77:185–92.PubMedCrossRef Vorechovsky I, Zetterquist H, Paganelli R, Koskinen S, Webster AD, Bjorkander J, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. 1995;77:185–92.PubMedCrossRef
9.
Zurück zum Zitat Agematsu K, Nagumo H, Yang FC, Nakazawa T, Fukushima K, Ito S, et al. B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol. 1997;27:2073–9.PubMedCrossRef Agematsu K, Nagumo H, Yang FC, Nakazawa T, Fukushima K, Ito S, et al. B cell subpopulations separated by CD27 and crucial collaboration of CD27+ B cells and helper T cells in immunoglobulin production. Eur J Immunol. 1997;27:2073–9.PubMedCrossRef
10.
Zurück zum Zitat Brouet JC, Chedeville A, Fermand JP, Royer B. Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol. 2000;30:2516–20.PubMedCrossRef Brouet JC, Chedeville A, Fermand JP, Royer B. Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol. 2000;30:2516–20.PubMedCrossRef
11.
Zurück zum Zitat Jacquot S, Macon-Lemaitre L, Paris E, Kobata T, Tanaka Y, Morimoto C, et al. 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;13:871–6.PubMedCrossRef Jacquot S, Macon-Lemaitre L, Paris E, Kobata T, Tanaka Y, Morimoto C, et al. 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;13:871–6.PubMedCrossRef
12.
Zurück zum Zitat Agematsu K, Futatani T, Hokibara S, Kobayashi N, Takamoto M, Tsukada S, et al. Absence of memory B cells in patients with common variable immunodeficiency. Clin Immunol. 2002;103:34–42.PubMedCrossRef Agematsu K, Futatani T, Hokibara S, Kobayashi N, Takamoto M, Tsukada S, et al. Absence of memory B cells in patients with common variable immunodeficiency. Clin Immunol. 2002;103:34–42.PubMedCrossRef
13.
Zurück zum Zitat Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385–400.PubMedCrossRef Piqueras B, Lavenu-Bombled C, Galicier L, Bergeron-van der Cruyssen F, Mouthon L, Chevret S, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23:385–400.PubMedCrossRef
14.
Zurück zum Zitat Warnatz K, Denz A, Dräger R, Braun M, Groth C, Wolff-Vorbeck G, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544–51.PubMedCrossRef Warnatz K, Denz A, Dräger R, Braun M, Groth C, Wolff-Vorbeck G, et al. Severe deficiency of switched memory B cells (CD27(+)IgM(−)IgD(−)) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. Blood. 2002;99:1544–51.PubMedCrossRef
15.
Zurück zum Zitat Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85.PubMedCrossRef Wehr C, Kivioja T, Schmitt C, Ferry B, Witte T, Eren E, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111:77–85.PubMedCrossRef
16.
Zurück zum Zitat Bryant A, Calver NC, Toubi E, Webster AD, 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;56:239–48.PubMedCrossRef Bryant A, Calver NC, Toubi E, Webster AD, 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;56:239–48.PubMedCrossRef
17.
Zurück zum Zitat Eisenstein EM, Jaffe JS, Strober W. Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation. J Clin Immunol. 1993;13:247–58.PubMedCrossRef Eisenstein EM, Jaffe JS, Strober W. Reduced interleukin-2 (IL-2) production in common variable immunodeficiency is due to a primary abnormality of CD4+ T cell differentiation. J Clin Immunol. 1993;13:247–58.PubMedCrossRef
18.
Zurück zum Zitat Stagg AJ, Funauchi M, Knight SC, Webster AD, Farrant J. Failure in antigen responses by T cells from patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 1994;96:48–53.PubMedCrossRef Stagg AJ, Funauchi M, Knight SC, Webster AD, Farrant J. Failure in antigen responses by T cells from patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 1994;96:48–53.PubMedCrossRef
19.
Zurück zum Zitat Thon V, Eggenbauer H, Wolf HM, Fischer MB, Litzman J, Lokaj J, et al. Antigen presentation by common variable immunodeficiency (CVID) B cells and monocytes is unimpaired. Clin Exp Immunol. 1997;108:1–8.PubMedCrossRef Thon V, Eggenbauer H, Wolf HM, Fischer MB, Litzman J, Lokaj J, et al. Antigen presentation by common variable immunodeficiency (CVID) B cells and monocytes is unimpaired. Clin Exp Immunol. 1997;108:1–8.PubMedCrossRef
20.
Zurück zum Zitat Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, et al. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J Immunol. 2009;182:5515–27.PubMedCrossRef Takahashi N, Matsumoto K, Saito H, Nanki T, Miyasaka N, Kobata T, et al. Impaired CD4 and CD8 effector function and decreased memory T cell populations in ICOS-deficient patients. J Immunol. 2009;182:5515–27.PubMedCrossRef
21.
Zurück zum Zitat Pandolfi F, Trentin L, San Martin JE, Wong JT, Kurnick JT, Moscicki RA. T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis. Clin Exp Immunol. 1992;89:198–203.PubMedCrossRef Pandolfi F, Trentin L, San Martin JE, Wong JT, Kurnick JT, Moscicki RA. T cell heterogeneity in patients with common variable immunodeficiency as assessed by abnormalities of T cell subpopulations and T cell receptor gene analysis. Clin Exp Immunol. 1992;89:198–203.PubMedCrossRef
22.
Zurück zum Zitat Farrant J, Spickett G, Matamoros N, Copas D, Hernandez M, North M, et al. Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID). Immunodeficiency. 1994;5:159–69.PubMed Farrant J, Spickett G, Matamoros N, Copas D, Hernandez M, North M, et al. Study of B and T cell phenotypes in blood from patients with common variable immunodeficiency (CVID). Immunodeficiency. 1994;5:159–69.PubMed
23.
Zurück zum Zitat Guazzi V, Aiuti F, Mezzaroma I, Mazzetta F, Andolfi G, Mortellaro A, et al. Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles. Clin Exp Immunol. 2002;129:346–53.PubMedCrossRef Guazzi V, Aiuti F, Mezzaroma I, Mazzetta F, Andolfi G, Mortellaro A, et al. Assessment of thymic output in common variable immunodeficiency patients by evaluation of T cell receptor excision circles. Clin Exp Immunol. 2002;129:346–53.PubMedCrossRef
24.
Zurück zum Zitat Moratto D, Gulino AV, Fontana S, Mori L, Pirovano S, Soresina A, et al. Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients. Clin Immunol. 2006;121:203–14.PubMedCrossRef Moratto D, Gulino AV, Fontana S, Mori L, Pirovano S, Soresina A, et al. Combined decrease of defined B and T cell subsets in a group of common variable immunodeficiency patients. Clin Immunol. 2006;121:203–14.PubMedCrossRef
25.
Zurück zum Zitat Giovannetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol. 2007;178:3932–43.PubMed Giovannetti A, Pierdominici M, Mazzetta F, Marziali M, Renzi C, Mileo AM, et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol. 2007;178:3932–43.PubMed
26.
Zurück zum Zitat Isgrò A, Marziali M, Mezzaroma I, Luzi G, Mazzone AM, Guazzi V, et al. Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency. J Immunol. 2005;174:5074–81.PubMed Isgrò A, Marziali M, Mezzaroma I, Luzi G, Mazzone AM, Guazzi V, et al. Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency. J Immunol. 2005;174:5074–81.PubMed
27.
Zurück zum Zitat Giovannetti A, Pierdominici M, Aiuti F. T-cell homeostasis: the dark(ened) side of common variable immunodeficiency. Blood. 2008;112:446–7.PubMedCrossRef Giovannetti A, Pierdominici M, Aiuti F. T-cell homeostasis: the dark(ened) side of common variable immunodeficiency. Blood. 2008;112:446–7.PubMedCrossRef
28.
Zurück zum Zitat Sottini A, Ghidini C, Zanotti C, Chiarini M, Caimi L, Lanfranchi A, et al. 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;136:217–27.PubMedCrossRef Sottini A, Ghidini C, Zanotti C, Chiarini M, Caimi L, Lanfranchi A, et al. 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;136:217–27.PubMedCrossRef
29.
Zurück zum Zitat van Zelm MC, Szczepanski T, van der Burg M, van Dongen JJM. Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion. J Exp Med. 2007;204:645–55.PubMedCrossRef van Zelm MC, Szczepanski T, van der Burg M, van Dongen JJM. Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion. J Exp Med. 2007;204:645–55.PubMedCrossRef
30.
Zurück zum Zitat Hazenberg MD, Verschuren MC, Hamann D, Miedema F, van Dongen JJ. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J Mol Med. 2001;79:631–40.PubMedCrossRef Hazenberg MD, Verschuren MC, Hamann D, Miedema F, van Dongen JJ. T cell receptor excision circles as markers for recent thymic emigrants: basic aspects, technical approach, and guidelines for interpretation. J Mol Med. 2001;79:631–40.PubMedCrossRef
31.
Zurück zum Zitat Fronkova E, Muzikova K, Mejstrikova E, Kovac M, Formankova R, Sedlacek P, et al. B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL. Bone Marrow Transplant. 2008;42:187–96.PubMedCrossRef Fronkova E, Muzikova K, Mejstrikova E, Kovac M, Formankova R, Sedlacek P, et al. B-cell reconstitution after allogeneic SCT impairs minimal residual disease monitoring in children with ALL. Bone Marrow Transplant. 2008;42:187–96.PubMedCrossRef
32.
Zurück zum Zitat Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708–12.PubMedCrossRef Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature. 1999;401:708–12.PubMedCrossRef
33.
Zurück zum Zitat Kimmig S, Przybylski GK, Schmidt CA, Laurisch K, Möwes B, Radbruch A, et al. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J Exp Med. 2002;195:789–94.PubMedCrossRef Kimmig S, Przybylski GK, Schmidt CA, Laurisch K, Möwes B, Radbruch A, et al. Two subsets of naive T helper cells with distinct T cell receptor excision circle content in human adult peripheral blood. J Exp Med. 2002;195:789–94.PubMedCrossRef
34.
Zurück zum Zitat Chiarini M, Sottini A, Ghidini C, Zanotti C, Serana F, Rottoli M, et al. Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. Mult Scler. 2010;16:218–27.PubMedCrossRef Chiarini M, Sottini A, Ghidini C, Zanotti C, Serana F, Rottoli M, et al. Renewal of the T-cell compartment in multiple sclerosis patients treated with glatiramer acetate. Mult Scler. 2010;16:218–27.PubMedCrossRef
35.
Zurück zum Zitat Maurer D, Fischer GF, Fae I, Majdic O, Stuhlmeier K, Von Jeney N, et al. IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset. J Immunol. 1992;148:3700–5.PubMed Maurer D, Fischer GF, Fae I, Majdic O, Stuhlmeier K, Von Jeney N, et al. IgM and IgG but not cytokine secretion is restricted to the CD27+ B lymphocyte subset. J Immunol. 1992;148:3700–5.PubMed
36.
Zurück zum Zitat Chen X, Barfield R, Benaim E, Leung W, Knowles J, Lawrence D, et al. Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients. Blood. 2005;105:886–93.PubMedCrossRef Chen X, Barfield R, Benaim E, Leung W, Knowles J, Lawrence D, et al. Prediction of T-cell reconstitution by assessment of T-cell receptor excision circle before allogeneic hematopoietic stem cell transplantation in pediatric patients. Blood. 2005;105:886–93.PubMedCrossRef
37.
Zurück zum Zitat Motta M, Chiarini M, Ghidini C, Zanotti C, Lamorgese C, Caimi L, et al. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients. J Transl Med. 2010;8:111.PubMedCrossRef Motta M, Chiarini M, Ghidini C, Zanotti C, Lamorgese C, Caimi L, et al. Quantification of newly produced B and T lymphocytes in untreated chronic lymphocytic leukemia patients. J Transl Med. 2010;8:111.PubMedCrossRef
38.
Zurück zum Zitat Lorenzi AR, Patterson AM, Pratt A, Jefferson M, Chapman CE, Ponchel F, et al. Determination of thymic function directly from peripheral blood: a validated modification to an established method. J Immunol Meth. 2008;339:185–94.CrossRef Lorenzi AR, Patterson AM, Pratt A, Jefferson M, Chapman CE, Ponchel F, et al. Determination of thymic function directly from peripheral blood: a validated modification to an established method. J Immunol Meth. 2008;339:185–94.CrossRef
39.
Zurück zum Zitat Pido-Lopez J, Imami N, Aspinall R. Both age and gender affect thymic output: more recent thymic migrants in females than males as they age. Clin Exp Immunol. 2001;125:409–13.PubMedCrossRef Pido-Lopez J, Imami N, Aspinall R. Both age and gender affect thymic output: more recent thymic migrants in females than males as they age. Clin Exp Immunol. 2001;125:409–13.PubMedCrossRef
40.
Zurück zum Zitat Ribeiro RM, Perelson AS. Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) data. Immunol Rev. 2007;216:21–34.PubMed Ribeiro RM, Perelson AS. Determining thymic output quantitatively: using models to interpret experimental T-cell receptor excision circle (TREC) data. Immunol Rev. 2007;216:21–34.PubMed
41.
Zurück zum Zitat Vlkova M, Thon V, Sarfyova M, Blaha L, Svobodnik A, Lokaj J, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–9.PubMedCrossRef Vlkova M, Thon V, Sarfyova M, Blaha L, Svobodnik A, Lokaj J, et al. Age dependency and mutual relations in T and B lymphocyte abnormalities in common variable immunodeficiency patients. Clin Exp Immunol. 2006;143:373–9.PubMedCrossRef
42.
Zurück zum Zitat Mouillot G, Carmagnat M, Gérard L, Garnier JL, Fieschi C, Vince N, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30:746–55.PubMedCrossRef Mouillot G, Carmagnat M, Gérard L, Garnier JL, Fieschi C, Vince N, et al. B-cell and T-cell phenotypes in CVID patients correlate with the clinical phenotype of the disease. J Clin Immunol. 2010;30:746–55.PubMedCrossRef
43.
Zurück zum Zitat De Vera MJ, Al Harthi L, Gewurz AT. Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles. Ann Allergy Asthma & Immunol. 2004;93:478–84.CrossRef De Vera MJ, Al Harthi L, Gewurz AT. Assessing thymopoiesis in patients with common variable immunodeficiency as measured by T-cell receptor excision circles. Ann Allergy Asthma & Immunol. 2004;93:478–84.CrossRef
44.
Zurück zum Zitat Spickett GP, Farrant J, North ME, Zhang JG, Morgan L, Webster AD. Common variable immunodeficiency: how many diseases? Immunol Today. 1997;18:325–8.PubMedCrossRef Spickett GP, Farrant J, North ME, Zhang JG, Morgan L, Webster AD. Common variable immunodeficiency: how many diseases? Immunol Today. 1997;18:325–8.PubMedCrossRef
45.
Zurück zum Zitat Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol. 2005;5:504–9.PubMedCrossRef Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol. 2005;5:504–9.PubMedCrossRef
46.
Zurück zum Zitat Douek DC, Betts MR, Hill BJ, Little SJ, Lempicki R, Metcalf JA, et al. Evidence for increased T cell turnover and decreased thymic output in HIV infection. J Immunol. 2001;167:6663–8.PubMed Douek DC, Betts MR, Hill BJ, Little SJ, Lempicki R, Metcalf JA, et al. Evidence for increased T cell turnover and decreased thymic output in HIV infection. J Immunol. 2001;167:6663–8.PubMed
47.
Zurück zum Zitat Vlková M, Fronková E, Kanderová V, Janda A, Ruzicková S, Litzman J, et al. Characterization of lymphocyte subsets in patients with common variable immunodeficiency reveals subsets of naive human B cells marked by CD24 expression. J Immunol. 2010;185:6431–8.PubMedCrossRef Vlková M, Fronková E, Kanderová V, Janda A, Ruzicková S, Litzman J, et al. Characterization of lymphocyte subsets in patients with common variable immunodeficiency reveals subsets of naive human B cells marked by CD24 expression. J Immunol. 2010;185:6431–8.PubMedCrossRef
48.
Zurück zum Zitat Banchereau J, Rousset F. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol. 1992;52:125–262.PubMedCrossRef Banchereau J, Rousset F. Human B lymphocytes: phenotype, proliferation, and differentiation. Adv Immunol. 1992;52:125–262.PubMedCrossRef
49.
Zurück zum Zitat Caraux A, Klein B, Paiva B, Bret C, Schmitz A, Fuhler GM, et al. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138− and CD138+ plasma cells. Haematologica. 2010;95:1016–20.PubMedCrossRef Caraux A, Klein B, Paiva B, Bret C, Schmitz A, Fuhler GM, et al. Circulating human B and plasma cells. Age-associated changes in counts and detailed characterization of circulating normal CD138− and CD138+ plasma cells. Haematologica. 2010;95:1016–20.PubMedCrossRef
50.
Zurück zum Zitat Treml LS, Quinn 3rd WJ, Treml JF, Scholz JL, Cancro MP. Manipulating B cell homeostasis: a key component in the advancement of targeted strategies. Arch Immunol Ther Exp. 2008;56:153–64.CrossRef Treml LS, Quinn 3rd WJ, Treml JF, Scholz JL, Cancro MP. Manipulating B cell homeostasis: a key component in the advancement of targeted strategies. Arch Immunol Ther Exp. 2008;56:153–64.CrossRef
51.
Zurück zum Zitat Boileau J, Mouillot G, Gérard L, Carmagnat M, Rabian C, Oksenhendler E, et al. Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study. J Autoimmun. 2011;36:25–32.PubMedCrossRef Boileau J, Mouillot G, Gérard L, Carmagnat M, Rabian C, Oksenhendler E, et al. Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study. J Autoimmun. 2011;36:25–32.PubMedCrossRef
Metadaten
Titel
Thymic and Bone Marrow Output in Patients with Common Variable Immunodeficiency
verfasst von
Federico Serana
Paolo Airò
Marco Chiarini
Cinzia Zanotti
Mirko Scarsi
Micol Frassi
Vassilios Lougaris
Alessandro Plebani
Luigi Caimi
Luisa Imberti
Publikationsdatum
01.08.2011
Verlag
Springer US
Erschienen in
Journal of Clinical Immunology / Ausgabe 4/2011
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-011-9526-6

Weitere Artikel der Ausgabe 4/2011

Journal of Clinical Immunology 4/2011 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.