Immunoactinopathies revisited: Understanding clinical manifestations and biological pathways.

Abstract

Immune cell functionality is highly dependent on the actin cytoskeleton. The actin cytoskeleton is regulated by a complex molecular machinery, involving multiple genes. Mutations in these genes can cause inborn errors of immunity, also termed immunoactinopathies, of which Wiskott Aldrich Syndrome is the best-characterized entity. At present, mutations in 23 genes can be considered causative of immunoactinopathies. Immunoactinopathies are rare disease entities with complex combinations of clinical manifestations, including immunodeficiency, immune dysregulation, malignancies, atopy, thrombocytopenia and bleeding, skin involvement or congenital defects. Prompt diagnosis is of crucial importance, as HSCT in an early phase can offer cure and prevent further complications. This review provides a detailed summary of the clinical experience with immunoactinopathies so far, elaborates on the most distinguishing features among immunoactinopathies by providing a clinical categorization, and links this information to the biological pathways that are involved. This information may be of help for clinicians to diagnose patients and eventually improve patient care.