Primary immunodeficiencies

• Published in: Journal of allergy and clinical immunology Vol. 125; no. 2; pp. S182 - S194
• Main Author: Notarangelo, Luigi D.
• Format: Journal Article
• Language: English
• Published: United States Mosby, Inc 01.02.2010; Elsevier Limited
• Subjects: Allergy and Immunology; Animals; Antibiotics; antibody deficiency; Apoptosis; Cytokines; Cytomegalovirus; Defects; Enzymes; gene therapy; Genetic Predisposition to Disease; Genetic Testing; Genetic Therapy; Genotype & phenotype; hematopoietic cell transplantation; Hematopoietic Stem Cell Transplantation; Human subjects; Humans; Immune system; Immunity, Cellular - genetics; Immunity, Innate - genetics; immunoglobulin replacement therapy; Immunoglobulins, Intravenous - therapeutic use; Immunologic Deficiency Syndromes - diagnosis; Immunologic Deficiency Syndromes - genetics; Immunologic Deficiency Syndromes - immunology; Immunologic Deficiency Syndromes - therapy; Infant, Newborn; innate immunity defects; Lymphocytes; Medical prognosis; Pathogenesis; Polymorphism, Genetic; Primary immunodeficiency; Streptococcus infections; T-cell immunodeficiency; CD40L; TAP; DP; CHS; WASP; MSMD; SHM; AID; immunoglobulin replacement therapy; CID; AD; gene therapy; IVIG; CMV; FOXP3; DHR-123; Primary immunodeficiency; BCR; AR; DGS; IRAK; RD; AT; MMR; TACI; hematopoietic cell transplantation; ANC; BTK; HCT; IPEX; SBDS; TREC; NK; NADPH; TCR; IgAD; AIRE; HLH; antibody deficiency; SCIG; WAS; XLA; SCID; HIES; UNG; CVID; THI; MBL; TLR; ICOS; CGD; innate immunity defects; CSR; T-cell immunodeficiency; Treg; PID; LAD; ALPS; SCIDX1; STAT; JAK; RAG; NHEJ; ADA; DC; SCN; Common variable immunodeficiency; Activation-induced cytidine deaminase; Leukocyte adhesion deficiency; Reticular dysgenesis; T-cell receptor; Hemophagocytic lymphohistiocytosis; IL-1 receptor–associated kinase; Combined immunodeficiency; Janus kinase; Transient hypogammaglobulinemia of infancy; Reduced nicotinamide adenine dinucleotide phosphate; Toll-like receptor; Wiskott-Aldrich syndrome; Dendritic cell; Chronic granulomatous disease; Double-positive; Subcutaneous immunoglobulin; Signal transducer and activator of transcription; Immune dysregulation–polyendocrinopathy–enteropathy–X-linked; X-linked severe combined immunodeficiency; X-linked agammaglobulinemia; Absolute neutrophil count; Dihydrorhodamine-123; Cytomegalovirus; Adenosine deaminase; Nonhomologous end-joining; Transmembrane activator and calcium modulator and cyclophilin ligand interactor; CD40 ligand; T-cell receptor excision circle; Autosomal recessive; Transporter of antigenic peptide; Autoimmune lymphoproliferative syndrome; Forkhead box protein 3; Mismatch repair; Recombinase-activating gene; Severe congenital neutropenia; Regulatory T; Autosomal dominant; Hyper-IgE syndrome; IgA deficiency; Uracil N-glycosidase; Wiskott-Aldrich syndrome protein; Bruton tyrosine kinase; Somatic hypermutation; Ataxia-telangiectasia; Natural killer; DiGeorge syndrome; Severe combined immunodeficiency; Autoimmune regulator; B-cell receptor; Inducible T-cell costimulator; Mannose-binding lectin; Intravenous immunoglobulin; Class-switch recombination; Mendelian susceptibility to mycobacterial disease; Chediak-Higashi syndrome; Schwachman-Bodian-Diamond syndrome
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2009.07.053

In the last years, advances in molecular genetics and immunology have resulted in the identification of a growing number of genes causing primary immunodeficiencies (PIDs) in human subjects and a better understanding of the pathophysiology of these disorders. Characterization of the molecular mechanisms of PIDs has also facilitated the development of novel diagnostic assays based on analysis of the expression of the protein encoded by the PID-specific gene. Pilot newborn screening programs for the identification of infants with severe combined immunodeficiency have been initiated. Finally, significant advances have been made in the treatment of PIDs based on the use of subcutaneous immunoglobulins, hematopoietic cell transplantation from unrelated donors and cord blood, and gene therapy. In this review we will discuss the pathogenesis, diagnosis, and treatment of PIDs, with special attention to recent advances in the field.