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CVID

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Humoral Primary Immunodeficiencies

Part of the book series: Rare Diseases of the Immune System ((RDIS))

Abstract

Common variable immunodeficiency (CVID) patients are individuals with antibody deficiency syndromes of various etiology and diverse clinical as well as immunological features. Clinical hallmarks are hypogammaglobulinemia and severe and/or frequent, chronic-recurring bacterial infections especially affecting the respiratory tract. Given that immunological and clinical presentations are by far more diverse and—since CVID per se is not a monogenetically defined disorder—there is a high chance of missed or incorrect diagnosis, since the “clinical picture perfect CVID patient” rarely encounters us in real life. Management of CVID consists of continuous replacement therapy with immunoglobulins, targeted antibiotic treatment of infections, and adequate therapy of complications. Allogenic peripheral stem cell therapy is considered today in patients with severe hematological changes (chronic transfusion-dependent anemia, leukopenia, thrombocytopenia), malignancies, and overall prognostically poor outcome despite consistent immunoglobulin substitution.

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References

  1. 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(3):190–7.

    Article  CAS  PubMed  Google Scholar 

  2. Malphettes M, et al. Late-onset combined immune deficiency: a subset of common variable immunodeficiency with severe T cell defect. Clin Infect Dis. 2009;49(9):1329–38.

    Article  CAS  PubMed  Google Scholar 

  3. Bertinchamp R, et al. Exclusion of patients with a severe T-cell defect improves the definition of common variable immunodeficiency. J Allergy Clin Immunol Pract. 2016;4(6):1147–57.

    Article  PubMed  Google Scholar 

  4. Wirsum C, et al. Secondary antibody deficiency in glucocorticoid therapy clearly differs from primary antibody deficiency. J Clin Immunol. 2016;36(4):406–12.

    Article  CAS  PubMed  Google Scholar 

  5. Bonilla FA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005;94(5 Suppl 1):S1–63.

    Article  PubMed  Google Scholar 

  6. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92(1):34–48.

    Article  CAS  PubMed  Google Scholar 

  7. Oksenhendler E, et al. Infections in 252 patients with common variable immunodeficiency. Clin Infect Dis. 2008;46(10):1547–54.

    Article  PubMed  Google Scholar 

  8. Tseng CW, et al. The incidence and prevalence of common variable immunodeficiency disease in Taiwan, a population-based study. PLoS One. 2015;10(10):e0140473.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Gathmann B, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(1):116–26.

    Article  PubMed  Google Scholar 

  10. Chapel H, et al. Common variable immunodeficiency disorders: division into distinct clinical phenotypes. Blood. 2008;112(2):277–86.

    Article  CAS  PubMed  Google Scholar 

  11. Vorechovsky I, et al. Family and linkage study of selective IgA deficiency and common variable immunodeficiency. Clin Immunol Immunopathol. 1995;77(2):185–92.

    Article  CAS  PubMed  Google Scholar 

  12. Aghamohammadi A, et al. Progression of selective IgA deficiency to common variable immunodeficiency. Int Arch Allergy Immunol. 2008;147(2):87–92.

    Article  CAS  PubMed  Google Scholar 

  13. Aghamohammadi A, et al. Clinical and immunological features of 65 Iranian patients with common variable immunodeficiency. Clin Diagn Lab Immunol. 2005;12(7):825–32.

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Schroeder HW Jr, et al. Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes. Mol Med. 1998;4(2):72–86.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kralovicova J, et al. Fine-scale mapping at IGAD1 and genome-wide genetic linkage analysis implicate HLA-DQ/DR as a major susceptibility locus in selective IgA deficiency and common variable immunodeficiency. J Immunol. 2003;170(5):2765–75.

    Article  CAS  PubMed  Google Scholar 

  16. Finck A, et al. Linkage of autosomal-dominant common variable immunodeficiency to chromosome 4q. Eur J Hum Genet. 2006;14(7):867–75.

    Article  CAS  PubMed  Google Scholar 

  17. Schaffer AA, et al. Analysis of families with common variable immunodeficiency (CVID) and IgA deficiency suggests linkage of CVID to chromosome 16q. Hum Genet. 2006;118(6):725–9.

    Article  PubMed  CAS  Google Scholar 

  18. Brodin P, et al. Variation in the human immune system is largely driven by non-heritable influences. Cell. 2015;160(1–2):37–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Rodriguez-Cortez VC, et al. Monozygotic twins discordant for common variable immunodeficiency reveal impaired DNA demethylation during naive-to-memory B-cell transition. Nat Commun. 2015;6:7335.

    Article  CAS  PubMed  Google Scholar 

  20. Warnatz K, 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(5):1544–51.

    Article  CAS  PubMed  Google Scholar 

  21. Piqueras B, et al. Common variable immunodeficiency patient classification based on impaired B cell memory differentiation correlates with clinical aspects. J Clin Immunol. 2003;23(5):385–400.

    Article  CAS  PubMed  Google Scholar 

  22. Wehr C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2008;111(1):77–85.

    Article  CAS  PubMed  Google Scholar 

  23. Giovannetti A, et al. Unravelling the complexity of T cell abnormalities in common variable immunodeficiency. J Immunol. 2007;178(6):3932–43.

    Article  CAS  PubMed  Google Scholar 

  24. 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(5):478–84.

    Article  PubMed  Google Scholar 

  25. Isgro A, et al. Bone marrow clonogenic capability, cytokine production, and thymic output in patients with common variable immunodeficiency. J Immunol. 2005;174(8):5074–81.

    Article  CAS  PubMed  Google Scholar 

  26. Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol. 2005;5(6):504–9.

    Article  PubMed  Google Scholar 

  27. Stuchly J, et al. Common variable immunodeficiency patients with a phenotypic profile of immunosenescence present with thrombocytopenia. Sci Rep. 2017;7:39710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Farrington M, et al. CD40 ligand expression is defective in a subset of patients with common variable immunodeficiency. Proc Natl Acad Sci U S A. 1994;91(3):1099–103.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Nordoy I, et al. Adhesion molecules in common variable immunodeficiency (CVID)--a decrease in L-selectin-positive T lymphocytes. Clin Exp Immunol. 1998;114(2):258–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pozzi N, et al. Defective surface expression of attractin on T cells in patients with common variable immunodeficiency (CVID). Clin Exp Immunol. 2001;123(1):99–104.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ferrer JM, et al. Alterations in interleukin secretion (IL-2 and IL-4) by CD4 and CD4 CD45RO cells from common variable immunodeficiency (CVI) patients. Clin Exp Immunol. 1995;102(2):286–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Fischer MB, et al. Defective interleukin-2 and interferon-gamma gene expression in response to antigen in a subgroup of patients with common variable immunodeficiency. J Allergy Clin Immunol. 1993;92(2):340–52.

    Article  CAS  PubMed  Google Scholar 

  33. Holm AM, et al. Impaired secretion of IL-10 by T cells from patients with common variable immunodeficiency—involvement of protein kinase A type I. J Immunol. 2003;170(11):5772–7.

    Article  CAS  PubMed  Google Scholar 

  34. Holm AM, et al. Abnormal interleukin-7 function in common variable immunodeficiency. Blood. 2005;105(7):2887–90.

    Article  CAS  PubMed  Google Scholar 

  35. North ME, Webster AD, Farrant J. Role of interleukin-2 and interleukin-6 in the mitogen responsiveness of T cells from patients with ‘common-variable’ hypogammaglobulinaemia. Clin Exp Immunol. 1990;81(3):412–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Taraldsrud E, et al. Defective IL-4 signaling in T cells defines severe common variable immunodeficiency. J Autoimmun. 2017;81:110–9.

    Article  CAS  PubMed  Google Scholar 

  37. Berron-Ruiz L, et al. Impaired selective cytokine production by CD4(+) T cells in common variable immunodeficiency associated with the absence of memory B cells. Clin Immunol. 2016;166–167:19–26.

    Article  PubMed  CAS  Google Scholar 

  38. Unger S, et al. The TH1 phenotype of follicular helper T cells indicates an IFN-gamma-associated immune dysregulation in patients with CD21low common variable immunodeficiency. J Allergy Clin Immunol. 2018;141(2):730–40.

    Article  CAS  PubMed  Google Scholar 

  39. Cunill V, et al. Follicular T cells from smB(−) common variable immunodeficiency patients are skewed toward a Th1 phenotype. Front Immunol. 2017;8:174.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Fischer MB, et al. A defect in the early phase of T-cell receptor-mediated T-cell activation in patients with common variable immunodeficiency. Blood. 1994;84(12):4234–41.

    CAS  PubMed  Google Scholar 

  41. Boncristiano M, et al. Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects. Eur J Immunol. 2000;30(9):2632–8.

    Article  CAS  PubMed  Google Scholar 

  42. Paccani SR, et al. Defective Vav expression and impaired F-actin reorganization in a subset of patients with common variable immunodeficiency characterized by T-cell defects. Blood. 2005;106(2):626–34.

    Article  CAS  PubMed  Google Scholar 

  43. Arumugakani G, Wood PM, Carter CR. Frequency of Treg cells is reduced in CVID patients with autoimmunity and splenomegaly and is associated with expanded CD21lo B lymphocytes. J Clin Immunol. 2010;30(2):292–300.

    Article  CAS  PubMed  Google Scholar 

  44. Horn J, et al. Decrease in phenotypic regulatory T cells in subsets of patients with common variable immunodeficiency. Clin Exp Immunol. 2009;156(3):446–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Melo KM, et al. A decreased frequency of regulatory T cells in patients with common variable immunodeficiency. PLoS One. 2009;4(7):e6269.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  46. Yu GP, et al. Regulatory T cell dysfunction in subjects with common variable immunodeficiency complicated by autoimmune disease. Clin Immunol. 2009;131(2):240–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Holm AM, et al. Gene expression analysis of peripheral T cells in a subgroup of common variable immunodeficiency shows predominance of CCR7(−) effector-memory T cells. Clin Exp Immunol. 2004;138(2):278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Viallard JF, et al. CD8+HLA-DR+ T lymphocytes are increased in common variable immunodeficiency patients with impaired memory B-cell differentiation. Clin Immunol. 2006;119(1):51–8.

    Article  CAS  PubMed  Google Scholar 

  49. Raeiszadeh M, et al. The T cell response to persistent herpes virus infections in common variable immunodeficiency. Clin Exp Immunol. 2006;146(2):234–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kuntz M, et al. Analysis of bulk and virus-specific CD8+ T cells reveals advanced differentiation of CD8+ T cells in patients with common variable immunodeficiency. Clin Immunol. 2011;141(2):177–86.

    Article  CAS  PubMed  Google Scholar 

  51. Holm AM, et al. Polyclonal expansion of large granular lymphocytes in common variable immunodeficiency—association with neutropenia. Clin Exp Immunol. 2006;144(3):418–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wong GK, et al. Accelerated loss of TCR repertoire diversity in common variable immunodeficiency. J Immunol. 2016;197(5):1642–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Resnick ES, et al. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119(7):1650–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Weston SA, et al. Assessment of male CVID patients for mutations in the Btk gene: how many have been misdiagnosed? Clin Exp Immunol. 2001;124(3):465–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Gaspar HB, Conley ME. Early B cell defects. Clin Exp Immunol. 2000;119(3):383–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Warnatz K, et al. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood. 2006;107(8):3045–52.

    Article  CAS  PubMed  Google Scholar 

  57. Warnatz K, et al. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans. Proc Natl Acad Sci U S A. 2009;106(33):13945–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Ochtrop ML, et al. T and B lymphocyte abnormalities in bone marrow biopsies of common variable immunodeficiency. Blood. 2011;118(2):309–18.

    Article  CAS  PubMed  Google Scholar 

  59. Alachkar H, et al. Memory switched B cell percentage and not serum immunoglobulin concentration is associated with clinical complications in children and adults with specific antibody deficiency and common variable immunodeficiency. Clin Immunol. 2006;120(3):310–8.

    Article  CAS  PubMed  Google Scholar 

  60. Detkova D, et al. Common variable immunodeficiency: association between memory B cells and lung diseases. Chest. 2007;131(6):1883–9.

    Article  PubMed  Google Scholar 

  61. Ko J, Radigan L, Cunningham-Rundles C. Immune competence and switched memory B cells in common variable immunodeficiency. Clin Immunol. 2005;116(1):37–41.

    Article  CAS  PubMed  Google Scholar 

  62. Vodjgani M, et al. Analysis of class-switched memory B cells in patients with common variable immunodeficiency and its clinical implications. J Investig Allergol Clin Immunol. 2007;17(5):321–8.

    CAS  PubMed  Google Scholar 

  63. Berglund LJ, Wong SW, Fulcher DA. B-cell maturation defects in common variable immunodeficiency and association with clinical features. Pathology. 2008;40(3):288–94.

    Article  CAS  PubMed  Google Scholar 

  64. Sanchez-Ramon S, et al. Memory B cells in common variable immunodeficiency: clinical associations and sex differences. Clin Immunol. 2008;128(3):314–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Cuss AK, et al. Expansion of functionally immature transitional B cells is associated with human-immunodeficient states characterized by impaired humoral immunity. J Immunol. 2006;176(3):1506–16.

    Article  CAS  PubMed  Google Scholar 

  66. Unger S, et al. Ill-defined germinal centers and severely reduced plasma cells are histological hallmarks of lymphadenopathy in patients with common variable immunodeficiency. J Clin Immunol. 2014;34(6):615–26.

    Article  CAS  PubMed  Google Scholar 

  67. Bonhomme D, et al. Impaired antibody affinity maturation process characterizes a subset of patients with common variable immunodeficiency. J Immunol. 2000;165(8):4725–30.

    Article  CAS  PubMed  Google Scholar 

  68. Andersen P, et al. Deficiency of somatic hypermutation of the antibody light chain is associated with increased frequency of severe respiratory tract infection in common variable immunodeficiency. Blood. 2005;105(2):511–7.

    Article  CAS  PubMed  Google Scholar 

  69. Almejun MB, et al. Noninfectious complications in patients with pediatric-onset common variable immunodeficiency correlated with defects in somatic hypermutation but not in class-switch recombination. J Allergy Clin Immunol. 2017;139(3):913–22.

    Article  CAS  PubMed  Google Scholar 

  70. Almejun MB, Borge M. Somatic hypermutation defects in common variable immune deficiency. Curr Allergy Asthma Rep. 2017;17(11):76.

    Article  PubMed  CAS  Google Scholar 

  71. Herbst EW, et al. Intestinal B cell defects in common variable immunodeficiency. Clin Exp Immunol. 1994;95(2):215–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Taubenheim N, et al. Defined blocks in terminal plasma cell differentiation of common variable immunodeficiency patients. J Immunol. 2005;175(8):5498–503.

    Article  CAS  PubMed  Google Scholar 

  73. Bryant A, et al. 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.

    Article  CAS  PubMed  Google Scholar 

  74. Driessen GJ, et al. B-cell replication history and somatic hypermutation status identify distinct pathophysiologic backgrounds in common variable immunodeficiency. Blood. 2011;118(26):6814–23.

    Article  CAS  PubMed  Google Scholar 

  75. Taraldsrud E, et al. Patterns of constitutively phosphorylated kinases in B cells are associated with disease severity in common variable immunodeficiency. Clin Immunol. 2017;175:69–74.

    Article  CAS  PubMed  Google Scholar 

  76. Visentini M, et al. Dysregulated extracellular signal-regulated kinase signaling associated with impaired B-cell receptor endocytosis in patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134(2):401–10.

    Article  CAS  PubMed  Google Scholar 

  77. Keller B, et al. Disturbed canonical nuclear factor of kappa light chain signaling in B cells of patients with common variable immunodeficiency. J Allergy Clin Immunol. 2017;139(1):220–31. e8

    Article  CAS  PubMed  Google Scholar 

  78. van de Ven AA, et al. Defective calcium signaling and disrupted CD20-B-cell receptor dissociation in patients with common variable immunodeficiency disorders. J Allergy Clin Immunol. 2012;129(3):755–61. e7

    Article  PubMed  CAS  Google Scholar 

  79. Schena F, et al. Dependence of immunoglobulin class switch recombination in B cells on vesicular release of ATP and CD73 ectonucleotidase activity. Cell Rep. 2013;3(6):1824–31.

    Article  CAS  PubMed  Google Scholar 

  80. Yu JE, et al. TLR-mediated B cell defects and IFN-alpha in common variable immunodeficiency. J Clin Immunol. 2012;32(1):50–60.

    Article  CAS  PubMed  Google Scholar 

  81. Clemente A, et al. B cells from common variable immunodeficiency patients fail to differentiate to antibody secreting cells in response to TLR9 ligand (CpG-ODN) or anti-CD40+IL21. Cell Immunol. 2011;268(1):9–15.

    Article  CAS  PubMed  Google Scholar 

  82. Barsotti NS, et al. IL-10-producing regulatory B cells are decreased in patients with common variable immunodeficiency. PLoS One. 2016;11(3):e0151761.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  83. Kofod-Olsen E, et al. Altered fraction of regulatory B and T cells is correlated with autoimmune phenomena and splenomegaly in patients with CVID. Clin Immunol. 2016;162:49–57.

    Article  CAS  PubMed  Google Scholar 

  84. Litinsky I, et al. Sarcoidosis: TB or not TB? Ann Rheum Dis. 2002;61(5):385–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Poeck H, et al. Plasmacytoid dendritic cells, antigen, and CpG-C license human B cells for plasma cell differentiation and immunoglobulin production in the absence of T-cell help. Blood. 2004;103(8):3058–64.

    Article  CAS  PubMed  Google Scholar 

  86. He B, et al. The transmembrane activator TACI triggers immunoglobulin class switching by activating B cells through the adaptor MyD88. Nat Immunol. 2010;11(9):836–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Ozcan E, et al. Transmembrane activator, calcium modulator, and cyclophilin ligand interactor drives plasma cell differentiation in LPS-activated B cells. J Allergy Clin Immunol. 2009;123(6):1277–86.e5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Groom JR, et al. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med. 2007;204(8):1959–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Treml LS, et al. TLR stimulation modifies BLyS receptor expression in follicular and marginal zone B cells. J Immunol. 2007;178(12):7531–9.

    Article  CAS  PubMed  Google Scholar 

  90. Ng LG, et al. BAFF costimulation of Toll-like receptor-activated B-1 cells. Eur J Immunol. 2006;36(7):1837–46.

    Article  CAS  PubMed  Google Scholar 

  91. Bayry J, et al. Common variable immunodeficiency is associated with defective functions of dendritic cells. Blood. 2004;104(8):2441–3.

    Article  CAS  PubMed  Google Scholar 

  92. Cunningham-Rundles C, Radigan L. Deficient IL-12 and dendritic cell function in common variable immune deficiency. Clin Immunol. 2005;115(2):147–53.

    Article  CAS  PubMed  Google Scholar 

  93. Scott-Taylor TH, et al. Monocyte derived dendritic cell responses in common variable immunodeficiency. Clin Exp Immunol. 2004;138(3):484–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Viallard JF, et al. Altered dendritic cell distribution in patients with common variable immunodeficiency. Arthritis Res Ther. 2005;7(5):R1052–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Yong PF, et al. Selective deficits in blood dendritic cell subsets in common variable immunodeficiency and X-linked agammaglobulinaemia but not specific polysaccharide antibody deficiency. Clin Immunol. 2008;127(1):34–42.

    Article  CAS  PubMed  Google Scholar 

  96. Cunningham-Rundles C, et al. TLR9 activation is defective in common variable immune deficiency. J Immunol. 2006;176(3):1978–87.

    Article  CAS  PubMed  Google Scholar 

  97. Marron TU, Yu JE, Cunningham-Rundles C. Toll-like receptor function in primary B cell defects. Front Biosci (Elite Ed). 2012;4:1853–63.

    Article  Google Scholar 

  98. Lanzavecchia A, et al. Understanding and making use of human memory B cells. Immunol Rev. 2006;211:303–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Ruprecht CR, Lanzavecchia A. Toll-like receptor stimulation as a third signal required for activation of human naive B cells. Eur J Immunol. 2006;36(4):810–6.

    Article  CAS  PubMed  Google Scholar 

  100. Bernasconi NL, Traggiai E, Lanzavecchia A. Maintenance of serological memory by polyclonal activation of human memory B cells. Science. 2002;298(5601):2199–202.

    Article  CAS  PubMed  Google Scholar 

  101. Taraldsrud E, et al. Common variable immunodeficiency revisited: normal generation of naturally occurring dendritic cells that respond to Toll-like receptors 7 and 9. Clin Exp Immunol. 2014;175(3):439–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Yu JE, et al. Toll-like receptor 7 and 9 defects in common variable immunodeficiency. J Allergy Clin Immunol. 2009;124(2):349–56, 356.e1–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. van de Ven AA, et al. B-cell defects in common variable immunodeficiency: BCR signaling, protein clustering and hardwired gene mutations. Crit Rev Immunol. 2011;31(2):85–98.

    Article  PubMed  Google Scholar 

  104. Ebbo M, et al. Innate lymphoid cells: major players in inflammatory diseases. Nat Rev Immunol. 2017;17(11):665–78.

    Article  CAS  PubMed  Google Scholar 

  105. Vely F, et al. Evidence of innate lymphoid cell redundancy in humans. Nat Immunol. 2016;17(11):1291–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Cols M, et al. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency. J Allergy Clin Immunol. 2016;137(4):1206–15. e6

    Article  CAS  PubMed  Google Scholar 

  107. Geier CB, et al. Reduced numbers of circulating group 2 innate lymphoid cells in patients with common variable immunodeficiency. Eur J Immunol. 2017;47(11):1959–69.

    Article  CAS  PubMed  Google Scholar 

  108. Gao Y, et al. Common variable immunodeficiency is associated with a functional deficiency of invariant natural killer T cells. J Allergy Clin Immunol. 2014;133(5):1420–8, 1428.e1.

    Article  CAS  PubMed  Google Scholar 

  109. Sanchez LA, et al. Two sides of the same coin: pediatric-onset and adult-onset common variable immune deficiency. J Clin Immunol. 2017;37(6):592–602.

    Article  CAS  PubMed  Google Scholar 

  110. Kralickova P, et al. Cytomegalovirus disease in patients with common variable immunodeficiency: three case reports. Int Arch Allergy Immunol. 2014;163(1):69–74.

    Article  PubMed  Google Scholar 

  111. Wheat WH, et al. Possible role of human herpesvirus 8 in the lymphoproliferative disorders in common variable immunodeficiency. J Exp Med. 2005;202(4):479–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Morimoto Y, Routes JM. Granulomatous disease in common variable immunodeficiency. Curr Allergy Asthma Rep. 2005;5(5):370–5.

    Article  CAS  PubMed  Google Scholar 

  113. Bates CA, et al. Granulomatous-lymphocytic lung disease shortens survival in common variable immunodeficiency. J Allergy Clin Immunol. 2004;114(2):415–21.

    Article  PubMed  Google Scholar 

  114. Ardeniz O, Cunningham-Rundles C. Granulomatous disease in common variable immunodeficiency. Clin Immunol. 2009;133(2):198–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Jorgensen SF, et al. A cross-sectional study of the prevalence of gastrointestinal symptoms and pathology in patients with common variable immunodeficiency. Am J Gastroenterol. 2016;111(10):1467–75.

    Article  PubMed  CAS  Google Scholar 

  116. Venhoff N, et al. The role of HLA DQ2 and DQ8 in dissecting celiac-like disease in common variable immunodeficiency. J Clin Immunol. 2013;33(5):909–16.

    Article  CAS  PubMed  Google Scholar 

  117. Washington K, et al. Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia. Am J Surg Pathol. 1996;20(10):1240–52.

    Article  CAS  PubMed  Google Scholar 

  118. Daniels JA, et al. Gastrointestinal tract pathology in patients with common variable immunodeficiency (CVID): a clinicopathologic study and review. Am J Surg Pathol. 2007;31(12):1800–12.

    Article  PubMed  Google Scholar 

  119. Ward C, et al. Abnormal liver function in common variable immunodeficiency disorders due to nodular regenerative hyperplasia. Clin Exp Immunol. 2008;153(3):331–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Fuss IJ, et al. Nodular regenerative hyperplasia in common variable immunodeficiency. J Clin Immunol. 2013;33(4):748–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Malamut G, et al. Nodular regenerative hyperplasia: the main liver disease in patients with primary hypogammaglobulinemia and hepatic abnormalities. J Hepatol. 2008;48(1):74–82.

    Article  PubMed  Google Scholar 

  122. Quinti I, et al. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007;27(3):308–16.

    Article  PubMed  Google Scholar 

  123. Seve P, et al. Autoimmune hemolytic anemia and common variable immunodeficiency: a case-control study of 18 patients. Medicine (Baltimore). 2008;87(3):177–84.

    Article  Google Scholar 

  124. Guffroy A, et al. Neutropenia in patients with common variable immunodeficiency: a rare event associated with severe outcome. J Clin Immunol. 2017;37(7):715–26.

    Article  CAS  PubMed  Google Scholar 

  125. Boileau J, et al. Autoimmunity in common variable immunodeficiency: correlation with lymphocyte phenotype in the French DEFI study. J Autoimmun. 2011;36(1):25–32.

    Article  CAS  PubMed  Google Scholar 

  126. Chapel H, et al. Confirmation and improvement of criteria for clinical phenotyping in common variable immunodeficiency disorders in replicate cohorts. J Allergy Clin Immunol. 2012;130(5):1197–8. e9

    Article  PubMed  Google Scholar 

  127. Mouillot G, et al. 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.

    Article  PubMed  Google Scholar 

  128. Oraei M, et al. Naive CD4+ T cells and recent thymic emigrants in common variable immunodeficiency. J Investig Allergol Clin Immunol. 2012;22(3):160–7.

    CAS  PubMed  Google Scholar 

  129. Maglione PJ. Autoimmune and lymphoproliferative complications of common variable immunodeficiency. Curr Allergy Asthma Rep. 2016;16(3):19.

    Article  PubMed  CAS  Google Scholar 

  130. van de Ven AA, Warnatz K. The autoimmune conundrum in common variable immunodeficiency disorders. Curr Opin Allergy Clin Immunol. 2015;15(6):514–24.

    Article  PubMed  CAS  Google Scholar 

  131. Podjasek JC, Abraham RS. Autoimmune cytopenias in common variable immunodeficiency. Front Immunol. 2012;3:189.

    Article  PubMed  PubMed Central  Google Scholar 

  132. Rensing-Ehl A, et al. Clinical and immunological overlap between autoimmune lymphoproliferative syndrome and common variable immunodeficiency. Clin Immunol. 2010;137(3):357–65.

    Article  CAS  PubMed  Google Scholar 

  133. Castigli E, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37(8):829–34.

    Article  CAS  PubMed  Google Scholar 

  134. Zhang L, et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. 2007;120(5):1178–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  135. Salzer U, et al. Screening of functional and positional candidate genes in families with common variable immunodeficiency. BMC Immunol. 2008;9:3.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Lee JJ, et al. Transmembrane activator and calcium-modulator and cyclophilin ligand interactor mutations in common variable immunodeficiency. Curr Opin Allergy Clin Immunol. 2008;8(6):520–6.

    Article  CAS  PubMed  Google Scholar 

  137. Verma N, et al. Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations. Clin Exp Immunol. 2017;190(1):1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Schubert D, et al. Autosomal dominant immune dysregulation syndrome in humans with CTLA4 mutations. Nat Med. 2014;20(12):1410–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  139. Gamez-Diaz L, et al. The extended phenotype of LPS-responsive beige-like anchor protein (LRBA) deficiency. J Allergy Clin Immunol. 2016;137(1):223–30.

    Article  CAS  PubMed  Google Scholar 

  140. Lopez-Herrera G, et al. Deleterious mutations in LRBA are associated with a syndrome of immune deficiency and autoimmunity. Am J Hum Genet. 2012;90(6):986–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Hou TZ, et al. Identifying functional defects in patients with immune dysregulation due to LRBA and CTLA-4 mutations. Blood. 2017;129(11):1458–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  142. Vorechovsky I, et al. Chromosomal radiosensitivity in common variable immune deficiency. Mutat Res. 1993;290(2):255–64.

    Article  CAS  PubMed  Google Scholar 

  143. Chua I, Quinti I, Grimbacher B. Lymphoma in common variable immunodeficiency: interplay between immune dysregulation, infection and genetics. Curr Opin Hematol. 2008;15(4):368–74.

    Article  PubMed  Google Scholar 

  144. Dhalla F, et al. Review of gastric cancer risk factors in patients with common variable immunodeficiency disorders, resulting in a proposal for a surveillance programme. Clin Exp Immunol. 2011;165(1):1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Mellemkjaer L, et al. Cancer risk among patients with IgA deficiency or common variable immunodeficiency and their relatives: a combined Danish and Swedish study. Clin Exp Immunol. 2002;130(3):495–500.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Seymour B, Miles J, Haeney M. Primary antibody deficiency and diagnostic delay. J Clin Pathol. 2005;58(5):546–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Roberts CA, et al. Investigation of common variable immunodeficiency patients and healthy individuals using autoimmune lymphoproliferative syndrome biomarkers. Hum Immunol. 2013;74(12):1531–5.

    Article  CAS  PubMed  Google Scholar 

  148. Rizzi M, et al. Outcome of allogeneic stem cell transplantation in adults with common variable immunodeficiency. J Allergy Clin Immunol. 2011;128(6):1371–4. e2

    Article  PubMed  Google Scholar 

  149. Wehr C, et al. Multicenter experience in hematopoietic stem cell transplantation for serious complications of common variable immunodeficiency. J Allergy Clin Immunol. 2015;135(4):988–97. e6

    Article  PubMed  Google Scholar 

  150. Ballow M, et al. Immunodeficiencies. Clin Exp Immunol. 2009;158(Suppl 1):14–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  151. Orange JS, et al. Use of intravenous immunoglobulin in human disease: a review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology. J Allergy Clin Immunol. 2006;117(4 Suppl):S525–53.

    Article  CAS  PubMed  Google Scholar 

  152. Gardulf A, et al. Subcutaneous immunoglobulin replacement in patients with primary antibody deficiencies: safety and costs. Lancet. 1995;345(8946):365–9.

    Article  CAS  PubMed  Google Scholar 

  153. Gardulf A, et al. Children and adults with primary antibody deficiencies gain quality of life by subcutaneous IgG self-infusions at home. J Allergy Clin Immunol. 2004;114(4):936–42.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Faculty of Medicine, Department of Rheumatology and Clinical Immunology, Medical Center—University of Freiburg, Freiburg im Breisgau, Germany

    Ulrich Salzer

  2. Faculty of Medicine, Center for Chronic Immunodeficiency (CCI), Medical Center—University of Freiburg, Freiburg im Breisgau, Germany

    Ulrich Salzer

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  1. Careggi Hospital, Department of Clinical and Experimental Medicine, University of Florence, Firenze, Italy

    Mario Milco D'Elios

  2. University Medical Centre Freiburg, Department of Rheumatology and Clinical Immunology and Center for Chronic Immunodeficiency, Freiburg, Germany

    Marta Rizzi

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Salzer, U. (2019). CVID. In: D'Elios, M., Rizzi, M. (eds) Humoral Primary Immunodeficiencies. Rare Diseases of the Immune System. Springer, Cham. https://doi.org/10.1007/978-3-319-91785-6_3

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