title: Restoring balance to B cells in ADA deficiency.
abstract: It is paradoxical that immunodeficiency disorders are associated with autoimmunity. Adenosine deaminase (ADA) deficiency, a cause of X-linked severe combined immunodeficiency (SCID), is a case in point. In this issue of the JCI, Sauer and colleagues investigate the B cell defects in ADA-deficient patients. They demonstrate that ADA patients receiving enzyme replacement therapy had B cell tolerance checkpoint defects. Remarkably, gene therapy with a retrovirus that expresses ADA resulted in the apparent correction of these defects, with normalization of peripheral B cell autoantibody frequencies. In vitro, agents that either block ADA or overexpress adenosine resulted in altered B cell receptor and TLR signaling. Collectively, these data implicate a B cell-intrinsic mechanism for alterations in B cell tolerance in the setting of partial ADA deficiency that is corrected by gene therapy.
authors.affiliation: Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19404, USA. luning@mail.med.upenn.edu
authors.forename: Eline T
authors.initials: ET
authors.lastname: Luning Prak
mesh_terms: D000243:Adenosine Deaminase / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007108:Immune Tolerance; D008297:Male; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000276:immunology* / Q000628:therapy*
chemical_list: D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; C548482:ADA protein, human; D000243:Adenosine Deaminase