A novel homozygous mutation in A20 is linked to Systemic Lupus Erythematosus onset at early childhood 4177

Abstract Description We report a novel homozygous mutation in the A20 protein responsible for early-onset lupus-like disease starting at four years of age. Although autosomal dominant A20 mutations have been identified to cause autoinflammatory disease, recessive A20 disease has not been previously described. The mutation, located in the seventh zinc finger domain of A20, compromises the protein’s ability to bind linear ubiquitin, consequently amplifying NFκB activation in HEK293 cells. We utilize immunoprecipitation to ascertain A20’s interaction with linear ubiquitin, coupled with flow cytometric analysis and western blotting to measure the expression of markers of NFκB activity following stimulation with TNFα. Our findings not only characterize a critical mutation contributing to early-onset lupus-like disease but also continue to highlight the important role of A20 in maintaining immune homeostasis. These functional insights into A20 and its protein interactions potentially pave the way for precision medicine approaches, offering new perspectives on therapeutic intervention in immunological disorders. Topic Categories Immune Mechanisms of Human Disease (HUM)