title: Modern management of primary T-cell immunodeficiencies.
abstract: The study of human T-cell PIDs with Mendelian inheritance has enabled the molecular characterization of important key functions and pathways in T-cell biology. In most cases, T-cell PIDs become apparent as combined T- and B-cell deficiencies. Severe combined immunodeficiencies (SCIDs) are characterized by a complete lack of T-cell development and, in some cases, a developmental block in other lymphoid lineages and manifest within the first year of life. Combined immunodeficiency syndromes (CIDs) result from hypomorphic mutations in typical SCID associated genes or from partial defects of T-cell development and manifest later in childhood by increased susceptibility to infection often combined with disturbances in immune homeostasis, e.g., autoimmunity and increased incidence in lymphoproliferation. The discovery of mutations and characterization of the cellular changes that underlie lymphocyte defects and immune dysregulation have led to novel, specific, successful therapies for severe diseases which are often fatal if left untreated. Over the last few years, impressive progress has been made in understanding the disease mechanisms of T-cell immunodeficiencies and in improving the long-term outcomes of potentially curative treatments, including gene therapy.
authors.affiliation: Division of Immunology, Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Switzerland.
authors.forename: Jana
authors.initials: J
authors.lastname: Pachlopnik Schmid
authors.forename: Tayfun
authors.initials: T
authors.lastname: Güngör
authors.forename: Reinhard
authors.initials: R
authors.lastname: Seger
mesh_terms: D000243:Adenosine Deaminase / Q000235:genetics; D002648:Child; D015329:Gene Rearrangement, T-Lymphocyte / Q000235:genetics; D015316:Genetic Therapy / Q000639:trends; D018380:Hematopoietic Stem Cell Transplantation / Q000639:trends; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007153:Immunologic Deficiency Syndromes / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D007165:Immunosuppression Therapy / Q000639:trends; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D000081207:Primary Immunodeficiency Diseases; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
chemical_list: D016756:Immunoglobulins, Intravenous; D053631:Interleukin Receptor Common gamma Subunit; D000243:Adenosine Deaminase
keywords: CID; Modern Management T-cell defects; T-cell immunodeficiencies; combined immunodeficiencies; gene therapy; hematopoietic stem cell transplantation; immunoglobulin substitution; severe combined immunodeficiencies, SCID; thymus transplantation