title: CHAI and LATAIE: new genetic diseases of CTLA-4 checkpoint insufficiency.
abstract: CTLA-4 is a critical inhibitory "checkpoint" molecule of immune activation. Several recent reports have described patients with immune dysregulation and lymphoproliferative disease resulting from 2 different genetic diseases that directly or indirectly cause CTLA-4 deficiency. Numerous articles have also been published describing CTLA-4 blockade in cancer immunotherapy and its side effects, which are ultimately the consequence of treatment-induced CTLA-4 deficiency. Here, we review these 2 diseases and CTLA-4 blockade therapy, emphasizing the crucial role of CTLA-4 in immune checkpoint regulation.
authors.affiliation: Division of Translational Medicine, Sidra Medical and Research Center, Doha, Qatar; Molecular Development of the Immune System Section, Laboratory of Immunology, Clinical Genomics Program.
authors.forename: Bernice
authors.identifier: 0000-0002-1087-6845
authors.initials: B
authors.lastname: Lo
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, Clinical Genomics Program.
authors.forename: Jill M
authors.identifier: 0000-0001-6626-7371
authors.initials: JM
authors.lastname: Fritz
authors.affiliation: Clinical Genomics Program, Human Immunological Diseases Section, Laboratory of Host Defenses, and.
authors.forename: Helen C
authors.identifier: 0000-0002-5582-9110
authors.initials: HC
authors.lastname: Su
authors.affiliation: Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD;
authors.forename: Gulbu
authors.initials: G
authors.lastname: Uzel
authors.affiliation: Division of Bone Marrow Transplantation and Immune Deficiency, Department of Pediatrics, and Division of Immunobiology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Jordan
authors.affiliation: Molecular Development of the Immune System Section, Laboratory of Immunology, Clinical Genomics Program.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Lenardo
mesh_terms: D060908:CTLA-4 Antigen / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D006801:Humans; D007154:Immune System Diseases / Q000235:genetics* / Q000628:therapy; D007167:Immunotherapy; D009154:Mutation / Q000235:genetics; D010641:Phenotype
chemical_list: D060908:CTLA-4 Antigen