Figure 1.
The illustration is divided into three sections: Genetics of HA20, Pathophysiology of HA20, and Phenotypes of HA20. The Genetics of HA20 section describes the etiology as heterozygous loss-of-function variants in TNFAIP3 on chromosome 6q23.3, with inheritance being autosomal dominant and possibly de novo. The Pathophysiology of HA20 section shows how A20 suppresses inflammatory signaling and how its loss leads to unchecked inflammation, involving TLR4, TNFR, and IFNAR pathways. The Phenotypes of HA20 section highlights the clinical heterogeneity of HA20 with a Venn diagram showing overlapping and diverse phenotypes including autoinflammation, immunodeficiency, autoimmunity, allergy, and lymphoproliferation.
HA20: Etiology, pathophysiology, and clinical phenotypes. Schematic presents a broad overview covering the genetic mechanism of HA20 (loss-of-function heterozygous variants in TNFAIP3), the immunology, and pathophysiology, including major pathways implicated in the immune dysregulation of HA20 and a selected list of HA20-associated phenotypes. PVS1, pathogenic very strong 1; TLR4, Toll-like receptor 4; TNFR, tumor necrosis factor receptor; NF-κB, nuclear factor κ-B; IFN, interferon; CVID, common variable immunodeficiency; ITP, immune thrombocytopenic purpura; AIHA, autoimmune hemolytic anemia; RA, rheumatoid arthritis; ALPS, autoimmune lymphoproliferative syndrome.