Common variable immune deficiency (CVID) is a genetic disease associated with enhanced susceptibility to infection, autoimmunity, and decreased antibody production. Mutations in the tumor necrosis factor receptor superfamily member TACI , are associated with CVID and autoimmunity development. Interestingly, autoimmunity develops in CVID patients with only one mutated copy of TACI , and CVID patients with two mutated TACI alleles do not develop autoimmunity.
In this issue of the Journal of Clinical Investigation , Eric Meffre and colleagues at Yale University evaluated B cell activation and tolerance development in healthy individuals and CVID patients with one or two mutated copies of TACI . The authors found that CVID patients with a single altered TACI allele maintained some residual B cell responsiveness that promoted development of autoantibodies, whereas individuals with 2 mutated copies of TACI have complete impairment of B cell responses, which likely prevents autoimmunity.
In the companion commentary, Antonia La Cava of the University of California Los Angeles suggests that targeting residual B cell activity in CVID patients that are heterozygous for TACI mutations may provide clinical relief.
TITLE: CVID-associated TACI mutations affect autoreactive B cell selection and activation
AUTHOR CONTACT: Eric Meffre
Yale University School of Medicine, New Haven, CT, USA
Phone: 1-203-737-4535; Fax: 1-203-785-7903; E-mail: eric.meffre@yale.edu
View this article at: http://www.jci.org/articles/view/69854?key=6b28b9a1ced274a85616
ACCOMPANYING COMMENTARY
TITLE: Common variable immunodeficiency: two mutations are better than one
AUTHOR CONTACT: Antonio La Cava
University of California Los Angeles, Los Angeles, CA, USA
Phone: 310-267-4975; Fax: 310 206-8606; E-mail: alacava@mednet.ucla.edu
View this article at: http://www.jci.org/articles/view/72476?key=89e682357107d9fc0553
Journal of Clinical Investigation