title: Primary immunodeficiencies due to abnormalities of the actin cytoskeleton.
abstract: Primary immunodeficiencies (PIDs) are inherited conditions where components of the immune system are missing or dysfunctional. Over 300 genes have been causally linked to monogenic forms of PID, including a number that regulate the actin cytoskeleton. The majority of cytoskeletal defects disrupt assembly and disassembly of filamentous actin in multiple immune cell lineages impacting functions such as cell migration and adhesion, pathogen uptake, intercellular communication, intracellular signalling, and cell division.
  
  
  
  In the past 24 months, new actin defects have been identified through next generation sequencing technologies. Substantial progress has also been made in understanding the pathogenic mechanisms that contribute to immunological dysfunction, and also how the cytoskeleton participates in normal physiological immune processes.
  
  
  
  This review summarises recent advances in the field, raising awareness of these conditions and our current understanding of their presentation. Description of further cases and new conditions will extend the clinical phenotype of actin-related disorders, and will promote the development of more effective and targeted therapies.
authors.affiliation: aUniversity College London Institute of Immunity and Transplantation bDepartment of Immunology, Royal Free London NHS Foundation Trust cUniversity College London Institute of Child Health dGreat Ormond Street Hospital for Children NHS Foundation Trust, London, UK.
authors.forename: Siobhan O
authors.initials: SO
authors.lastname: Burns
authors.forename: Anton
authors.initials: A
authors.lastname: Zarafov
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000209:etiology* / Q000378:metabolism*; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008840:Microfilament Proteins / Q000172:deficiency; D011485:Protein Binding; D055503:Protein Multimerization; D016511:Severe Combined Immunodeficiency / Q000209:etiology / Q000378:metabolism; D015398:Signal Transduction; D015534:Trans-Activators / Q000172:deficiency
chemical_list: C402110:DOCK2 protein, human; C516591:DOCK8 protein, human; D020690:GTPase-Activating Proteins; D020662:Guanine Nucleotide Exchange Factors; C431575:MRTFA protein, human; D008840:Microfilament Proteins; D015534:Trans-Activators; C071058:moesin