title: 2. Update on primary immunodeficiency diseases.
abstract: The pace of discovery in primary immunodeficiency continues to accelerate. In particular, lymphocyte defects have been the source of the most impressive expansion in recent years. Novel forms of agammaglobulinemia, class-switch defects, and T-B(+) severe combined immunodeficiency have been described. Little by little, the genetic heterogeneity of the common variable immunodeficiency and IgA deficiency phenotypes continues to be unraveled as new molecular defects have been reported in these patients as well. The phenotypic spectrum of DiGeorge syndrome has been further developed, along with promising advances in therapy. Defects of nuclear factor kappaB regulation and Toll-like receptor signaling have been described, along with defects of chemokine receptors and cytoplasmic proteases. Clinically defined immunodeficiencies, such as hyper-IgE syndrome and idiopathic CD4 lymphocytopenia, are also discussed. Finally, significant adverse effects in some patients have tempered initial enthusiasm for gene therapy.
authors.affiliation: Division of Immunology, Children's Hospital, Fegan Bldg. 6th Floor, 300 Longwood Avenue, Boston, MA 02115, USA. francisco.bonilla@childrens.harvard.edu
authors.forename: Francisco A
authors.initials: FA
authors.lastname: Bonilla
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000361:Agammaglobulinemia / Q000235:genetics / Q000276:immunology; D004062:DiGeorge Syndrome / Q000276:immunology / Q000628:therapy; D015316:Genetic Therapy; D017098:IgA Deficiency / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000276:immunology* / Q000628:therapy; D007589:Job Syndrome / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D010447:Peptide Hydrolases / Q000172:deficiency; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics; D016511:Severe Combined Immunodeficiency / Q000276:immunology / Q000628:therapy; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology; D051193:Toll-Like Receptors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D019707:Receptors, Chemokine; D051193:Toll-Like Receptors; D010447:Peptide Hydrolases