Common variable immunodeficiency.
Common variable immunodeficiency is the most prevalent clinically significant antibody deficiency at all ages. The disorder is defined principally by characteristic infection susceptibility with hypogammaglobulinemia and impaired-specific antibody response. Several recent large registry-based studies have defined distinct phenotypic subtypes. Several studies have also correlated specific immunologic markers with these phenotypes. The biochemical or genetic abnormality in the majority of patients remains unknown. Recently, several molecular genetic lesions have been defined. Among these, mutations of inducible costimulator, and CD19, appear to be disease causing by themselves. These account for about 1% of cases. Other mutations or polymorphisms, such as in the human homolog of Escherichia coli MutS 5 (MSH5), and transmembrane activator and calcium mobilizing ligand interactor, seem to be disease associated in 5-10% of patients, but may require additional immunologic abnormalities for full expression of the phenotype, as unaffected heterozygotes have also been described.
Bonilla
Francisco A
FA
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts 02115, USA. francisco.bonilla@childrens.harvard.edu
Geha
Raif S
RS
D017074:Common Variable Immunodeficiency / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology / Q000503:physiopathology; D006801:Humans; D011110:Polymorphism, Genetic