Common Variable Immunodeficiency

In addition, the accompanying diseases and sequelae of CVID require adequate treatment. Corticosteroids and cyclosporine A are effective for granulomatous manifestations and autoimmune diseases, although long-term treatment efficacy may be limited due to side effects.

From recent case reports, novel monoclonal anti-B-cell antibodies are promising new agents to combat autoimmune and granulomatous complications in CVID. However their effectiveness needs to be assessed in systematic double-blind, randomized clinical trials.

Conclusion

CVID comprises a genetically and clinically heterogeneous group of diseases in which diagnosis is often delayed or even missed. In the majority of cases, CVID remains a clinical diagnosis of exclusion. However, the identification of the first genetic defects associated with a CVID phenotype mark substantial progress for clinical immunology. These findings not only allow a definite diagnosis in a small subgroup of patients, but also serve as models for understanding the pathogenesis of CVID as well as the function of the normal immune system. The discovery of additional genes associated with CVID and the mechanisms by which the mutation promotes CVID will be essential for the future diagnosis and treatment of this disease. Genetic testing may also reduce the time delay between onset of initial symptoms and diagnosis, improving patient outcomes.

Drs. Myrtek and Salzer are researchers in the division of rheumatology and clinical immunology at the Medical School of the University Hospital Freiburg in Hugstetterstr, Germany.

References

1. Janeway CA, Apt L, Gitlin D. Agammaglobulinemia. Trans Assoc Am Physicians. 1953;66:200-202.
2. International Union of Immunological Societies. Primary immunodeficiency diseases. Report of an IUIS Scientific Committee. Clin Exp Immunol. 1999;118:1-28.
3. Cunningham-Rundles C, Bodian C. Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol. 1999;92:34-48.
4. Wang J, Cunningham-Rundles C. Treatment and outcome of autoimmune hematologic disease in common variable immunodeficiency (CVID). J Autoimmun. 2005;25:57-62.
5. Wehr C, Kivioja T, Schmitt C, et al. The EUROclass trial: defining subgroups in common variable immunodeficiency. Blood. 2007; doi:10.1182/blood-2007-06-091744
6. Piqueras B, Lavenu-Bombled C, Galicier L, 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.
7. Warnatz K, Denz A, Drager R, 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;99:1544-1551.
8. Goldacker S, Draeger R, Warnatz K, et al. Active vaccination in patients with common variable immunodeficiency (CVID). Clin Immunol. 2007;124:294-303.
9. Schäffer AA, Salzer U, Hammarström L, Grimbacher B. Deconstructing common variable immunodeficiency by genetic analysis. Curr Opin Genet Dev. 2007;17:201-212.
10. Grimbacher B, Hutloff A, Schlesier M, et al. Homozygous loss of ICOS is associated with adult-onset common variable immunodeficiency. Nat Immunol. 2003;4:261-268.
11. Bossaller L, Burger J, Draeger R, et al. ICOS deficiency is associated with a severe reduction of CXCR5+CD4 germinal center Th cells. J Immunol. 2006;177:4927-4932.
12. Warnatz K, Bossaller L, Salzer U, et al. Human ICOS deficiency abrogates the germinal center reaction and provides a monogenic model for common variable immunodeficiency. Blood. 2006;107:3045-3052.
13. Salzer U, Chapel HM, Webster AD, et al. Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans. Nat Genet. 2005;37:820-828.
14. Castigli E, Wilson SA, Garibyan L, et al. TACI is mutant in common variable immunodeficiency and IgA deficiency. Nat Genet. 2005;37:829-834.
15. Pan-Hammarström Q, Salzer U, Du L, et al. Reexamining the role of TACI coding variants in common variable immunodeficiency and selective IgA deficiency. Nat Genet. 2007;39:429-430.
16. Zhang L, Radigan L, Salzer U, 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;120:1178-1185.
17. van Zelm MC, Reisli I, van der Burg M, et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006; 354:1901-1912.
18. Kanegane H, Agematsu K, Futatani T, et al. Novel mutations in a Japanese patient with CD19 deficiency. Genes Immun. 2007; doi: 10.1038/sj.gene.6364431
19. Warnatz K, Salzer U, Gutenberger S, et al. Finally found: human BAFF-R deficiency causes CVID. XIth Meeting of the European Society for Immunodeficiencies. 2004;21-24.