Common variable immunodeficiency

The diagnosis of common variable immunodeficiency (CVID) remains unsatisfactory and depends on the exclusion of other known single gene disorders causing hypoimmunoglobulinemia. The pattern, however, in a substantial proportion of patients is one of chronic immune activation, failure of T-cell help for antibody production, and a marked skewing toward a TH1 cytokine profile manifested clinically as a widespread mucosal inflammation and multiorgan granulomas. Genetic studies confirm that many patients have a complex polygenic disease, with a major susceptibility locus in the major histocompatibility complex on chromosome 6. In general, the prognosis is good provided that meticulous attention is paid to preventing and treating complications such as Haemophilus influenzae colonization of the lungs, mycoplasma infection in the joints, lungs, and urinary tract, and enteroviral infection in the central nervous system. Although steroids are useful for the unexplained chronic mucosal inflammation in the bowel and multisystem granulomas that are now a major cause of morbidity and mortality, new therapeutic approaches for these complications are needed.