Skip to main content

Advertisement

SpringerLink
Log in

Common variable immunodeficiency

  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Common variable immunodeficiency (CVID) is a common primary immnodeficiency disease, the hallmark of which is hypogammaglobulinemia. Due to the lack of antibodies, patients usually have recurrent bacterial infections, but there are a number of other puzzling manifestations, including inflammatory conditions, autoimmune disease, and the development of lymphomas. Most patients are diagnosed as adults, and delay in the recognition of the antibody defect is comon. A number of defects of T cell function and deficits in the memory B cell pool have been identified, but the underlying cause of this defect remains unknown.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. International Union of Immunological Societies: Primary immunodeficiency diseases: report of an IUIS scientific committee. Clin Exp Immunol 1999, 118(suppl 1):1–28. This is a recent compilation of the currently defined primary immune deficiency diseases.

    Google Scholar 

  2. Cunningham-Rundles C, Bodian C: Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 1999, 92:34–48. This is a recent overview of a large cohort of patients with common variable immunodeficiency in the United States. It includes incidence of manifestations, immune parameters, predictors of immune status, and mortality.

    Article  PubMed  CAS  Google Scholar 

  3. Hermaszewski RA, Webster ADB. Primary hypogammaglobulinemia: a survey of clinical manifestations and complications. Q J Med 1993, 86:31–42.

    PubMed  CAS  Google Scholar 

  4. Hammarstrom L, Vorechovsky I, Webster D: Selective IgA deficiency (SIgAD) and common variable immunodeficiency (CVID). Clin Exp Immunol 2000, 120:225–231. This is a succinct recent review of common variable immunodeficiency and the related disease, selective IgA deficiency.

    Article  PubMed  CAS  Google Scholar 

  5. Janeway CA, Apt L, Gitlin D: Agammaglobulinemia. Trans Assoc Am Physicians 1953, 66:200.

    PubMed  CAS  Google Scholar 

  6. Bryant A, Calver NC, Toubi E, et al.: Classification of patients with common variable immunodeficiency by B-cell secretion of IgM and IgG response to anti-IgM and interleukin 2. Clin Immunol Immunopathol 1990, 56:239–248.

    Article  PubMed  CAS  Google Scholar 

  7. Shovlin CL, Simmonds HA, Fairbanks LD, et al.: Adult onset immunodeficiency caused by inherited adenosine deaminase deficiency. J Immunol 1994, 153:2331–2339.

    PubMed  CAS  Google Scholar 

  8. Hermans PE, Diaz-Buxo JA, Stobo JD: Idiopathic late-onset immunoglobulin deficiency: clinical observation in 50 patients. Am J Med 1976, 61:221–237.

    Article  PubMed  CAS  Google Scholar 

  9. Cunningham-Rundles C: Clinical and immunologic analyses of 103 patients with common variable immunodeficiency. J Clin Immunol 1989, 9:22–23.

    Article  PubMed  CAS  Google Scholar 

  10. Webster ADB, Taylor-Robinson D, Furr PM, Asherson GL: Mycoplasmal (ureaplasma) septic arthritis in hypogammaglobulinemia. BMJ 1978, 1:478–479.

    Article  PubMed  CAS  Google Scholar 

  11. Roifman CM, Rao CP, Lederman HM, et al.: Increased susceptibility to mycoplasma infection in patients with hypogammaglobulinemia. Am J Med 1986, 80:590–594.

    Article  PubMed  CAS  Google Scholar 

  12. Esolen LM, Fasano MB, Flynn J, et al.: Pneumocystis carinii osteomyelitis in a patient with common variable immunodeficiency. N Engl J Med 1992, 326:999–1001.

    Article  PubMed  CAS  Google Scholar 

  13. Washington K, Stenzel TT, Buckley RH, Gottfried MR: Gastrointestinal pathology in patients with common variable immunodeficiency and X-linked agammaglobulinemia. Am J Pathol 1996, 20:1240–1252.

    Article  CAS  Google Scholar 

  14. Zullo A, Romiti A, Rinaldi V, et al.: Gastric pathology in patients with common variable immunodeficiency. Gut 1999 45:77–81.

    Article  PubMed  CAS  Google Scholar 

  15. Fasano MD, Sullivan KE, Sarpong SB, et al.: Sarcoidosis and common variable immunodeficiency: report of 8 cases and review of the literature. Medicine (Baltimore) 1996, 75:251–261.

    Article  CAS  Google Scholar 

  16. Mechanic LJ, Dikman S, Cunningham-Rundles C: Granulomatous disease in common variable immunodeficiency. Ann Intern Med 1997, 127:613–617.

    PubMed  CAS  Google Scholar 

  17. Mullighan CG, Fanning GC, Chapel HM, Welsh KI: TNF and lymphotoxin-alpha polymorphisms associated with common variable immunodeficiency: role in the pathogenesis of granulomatous disease. J Immunol 1997, 159:6236–6241.

    PubMed  CAS  Google Scholar 

  18. Cunningham-Rundles C, Siegal FP, Cunningham-Rundles S, Lieberman P: Incidence of cancer in 98 patients with common varied immunodeficiency. J Clin Immunol 1987, 7:294–299.

    Article  PubMed  CAS  Google Scholar 

  19. Cunningham-Rundles C, Lieberman P, Hellman G, Chaganti RS: Non-Hodgkin’s lymphoma in common variable immunodeficiency. Am J Hematol 1991, 37:69–74.

    Article  PubMed  CAS  Google Scholar 

  20. Sander CA, Medeiros J, Weiss LW, et al.: Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome. Am J Surg Pathol 1992, 16:1170–1182.

    Article  PubMed  CAS  Google Scholar 

  21. Ariatti C, Vivenza D, Capello D, et al.: Common-variable immunodeficiency-related lymphomas associate with mutations and rearrangements of BCL-6: pathogenetic and histogenetic implications. Hum Pathol 2000, 31:871–873.

    Article  PubMed  CAS  Google Scholar 

  22. Fiorilli M, Crescenzi M, Carbonari M, et al.: Phenotypically immature IgG bearing B cells in patients with hypogammaglobulinemia. J Clin Immunol 1986, 6:21–25.

    Article  PubMed  CAS  Google Scholar 

  23. Ralph P, Jeong G, Nakuinz I, et al.: Rescue of IgM, and IgA production in common varied immunodeficiency by T cell independent stimulation with Epstein-Barr virus. J Clin Immunol 1985, 5:122–129.

    Article  PubMed  Google Scholar 

  24. Levy Y, Gupta N, Le Deist F, et al.: Defect in IgV gene somatic hypermutation in common variable immuno-deficiency syndrome. Proc Natl Acad Sci U S A 1998, 95:13135–13140. This article reports observation of a few patients with CVID who had an interesting and important defect in the B-cell memory pool, restricting antibody diversity.

    Article  PubMed  CAS  Google Scholar 

  25. Brouet JC, Chedeville A, Fermand JP, Royer B: Study of the B cell memory compartment in common variable immunodeficiency. Eur J Immunol 2000, 30:2516–2520. This report describes work investigating the development of the B-cell memory pool in CVID; a paucity of these cells and a lack of memory cells after stimulation were found.

    Article  PubMed  CAS  Google Scholar 

  26. Cunningham-Rundles S, Cunningham-Rundles C, Siegal FP, et al.: Defective cellular immune response in vitro in common variable immunodeficiency. J Clin Immunol 1981, 1:65–72.

    Article  PubMed  CAS  Google Scholar 

  27. North ME, Spickett GP, Allsop J, et al.: Defective DNA synthesis by T cells in acquired common variable hypogammaglobulinemia on stimulation with mitogens. Clin Exp Immunol 1989, 76:19–23.

    PubMed  CAS  Google Scholar 

  28. Kondratenko I, Amlot PL, Webster AD, Farrant J: Lack of specific antibody response in common variable immunodeficiency (CVID) associated with failure in production of antigen-specific memory T cells: MRC Immunodeficiency Group. Clin Exp Immunol 1997, 108:9–13.

    Article  PubMed  CAS  Google Scholar 

  29. Di Renzo M, Zhou Z, George I, et al.: Enhanced apoptosis of T cells in common variable immunodeficiency (CVID): role of defective CD28 co-stimulation. Clin Exp Immunol 2000, 120:503.

    Article  Google Scholar 

  30. Guo BC, Saxon A: B cell lines from a subset of patients with common variable immunodeficiency undergo enhanced apoptosis associated with an increased display of CD95 (Apo-1/fas), diminished CD38 expression, and decreased IgG and IgA production. Cell Immunol 1995, 166:83–92.

    Article  PubMed  CAS  Google Scholar 

  31. Iglesias J, Matamoros N, Raga S, et al.: CD95 expression and function on lymphocyte subpopulations in common variable immunodeficiency (CVID); related to increased apoptosis. Clin Exp Immunol 1999, 117:138–146.

    Article  PubMed  CAS  Google Scholar 

  32. Kruger G, Welte K, Ciobanu N, et al.: Interleukin 2 correction of defective in vitro T cell mitogenesis in patients with common varied immunodeficiency. J Clin Immunol 1984, 4:295–303.

    Article  PubMed  CAS  Google Scholar 

  33. Pastorelli G, Roncarolo MG, Touraine JL, et al.: Peripheral blood lymphocytes of patients with common variable immunodeficiency produce reduced levels of interleukin-4, interleukin-2 and interferon-gamma, but proliferate normally upon activation with mitogens. Clin Exp Immunol 1989, 78:334–340.

    PubMed  CAS  Google Scholar 

  34. Sneller MC, Strober W: Abnormalities of lymphokine gene expression in patients with common variable immunodeficiency. J Immunol 1990, 144:3762–3769.

    PubMed  CAS  Google Scholar 

  35. Zhou Z, Huang R, Danon M, et al.: IL-10 production in common variable immunodeficiency. Clin Immunol Immunopathol 1998, 86:298–304.

    Article  PubMed  CAS  Google Scholar 

  36. Aukrust P, Aandahl EM, Skalhegg BS, et al.: Increased activation of protein kinase A type I contributes to the T cell deficiency in common variable immunodeficiency. J Immunol 1999, 162:1178–1185.

    PubMed  CAS  Google Scholar 

  37. Fischer MB, Hauber J, Eggenbauer H, et al.: A defect in the early phase of T-cell receptor mediated T-cell activation in patients with common variable immunodeficiency. Blood 1994, 84:4234–4241.

    PubMed  CAS  Google Scholar 

  38. Boncristiano M, Majolini MB, D’Elios MM, et al.: Defective recruitment and activation of ZAP-70 in common variable immunodeficiency patients with T cell defects. Eur J Immunol 2000, 30:2632–2638. This article describes a signaling abnormality in the T-cell receptor, resulting in diminished ZAP-70 mobilization.

    Article  PubMed  CAS  Google Scholar 

  39. Farrington M, Grosmaire LS, Nonoyoma S, et al.: CD40 ligand expression is defective in a subset of patients with common variable immunodeficiency. Proc Natl Acad Sci U S A 1994, 91:1099–1103.

    Article  PubMed  CAS  Google Scholar 

  40. Nonoyama S, Farrington ML, Ochs HD: Effect of IL-2 on immunoglobulin production by anti-CD40-activated human B cells: synergistic effect with IL-10 and antagonistic effect with IL-4. Clin Immunol Immunopathol 1994, 72:373–379.

    Article  PubMed  CAS  Google Scholar 

  41. Aukrust P, Berge RK, Muller F, et al.: Elevated plasma levels of reduced homocysteine in common variable immunodeficiency-a marker of enhanced oxidative stress. Eur J Clin Invest 1997, 27:723–730.

    Article  PubMed  CAS  Google Scholar 

  42. Cambronero R, Sewell WA, North ME, et al.: Up-regulation of IL-12 in monocytes: a fundamental defect in common variable immunodeficiency. J Immunol 2000, 164:488–494.

    PubMed  CAS  Google Scholar 

  43. Schroeder HW Jr, Zhu ZB, March RE, et al.: Susceptibility locus for IgA deficiency and common variable immunodeficiency in the HLA-DR3, -B8, -A1 haplotypes. Mol Med 1998, 4:72–86. The relationship of the MHC to the development of CVCID and its relative, selective IgA deficiency continues to be an important theme in the understanding of these immune defects.

    PubMed  CAS  Google Scholar 

  44. Vorechovsky I, Webster AD, Plebani A, Hammarstrom L: Genetic linkage of IgA deficiency to the major histocompatibility complex: evidence for allele segregation distortion, parent-of-origin penetrance differences, and the role of anti-IgA antibodies in disease predisposition. Am J Hum Genet 1999, 64:1096–1109. This article explores the relationship of the MHC to the development of CVCID and selective IgA deficiency and points out again that the parent of origin is an intriguing fact of inheritance.

    Article  PubMed  CAS  Google Scholar 

  45. Cunningham-Rundles C, Siegal FP, Smithwick EM, et al.: Efficacy of intravenous immunoglobulin in primary humoral immunodeficiency disease. Ann Intern Med 1984, 101:435–439.

    PubMed  CAS  Google Scholar 

  46. Stiehm ER: Human intravenous immunoglobulin in primary and secondary antibody deficiencies. Pediatr Infect Dis J 1997, 16:696–707.

    Article  PubMed  CAS  Google Scholar 

  47. Davies CW, Juniper MC, Gray W, et al.: Lymphoid interstitial pneumonitis associated with common variable hypogammaglobulinaemia treated with cyclosporin A. Thorax 2000, 55:88–90.

    Article  PubMed  CAS  Google Scholar 

  48. Yeatman M, McNeil K, Smith JA, et al.: Lung transplantation in patients with systemic diseases: an eleven-year experience at Papworth Hospital. J Heart Lung Transplant 1996, 15:144–149.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Clinical Immunology, Departments of Medicine and Pediatrics, Mount Sinai Medical Center, 1425 Madison Avenue, 10029, New York, NY, USA

    Charlotte Cunningham-Rundles MD, PhD

Authors
  1. Charlotte Cunningham-Rundles MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cunningham-Rundles, C. Common variable immunodeficiency. Curr Allergy Asthma Rep 1, 421–429 (2001). https://doi.org/10.1007/s11882-001-0027-1

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11882-001-0027-1

Keywords

Search

Navigation