CRIA Syndrome: Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome:

Abstract

CRIA syndrome (Cleavage-Resistant RIPK1-Induced Autoinflammatory Syndrome) is an extremely rare, chronic, autosomal dominantly inherited autoinflammatory disease. It was discovered in late 2019 by researchers at the National Human Genome Research Institute. It is caused by gain-of-function (GoF) mutations in the RIPK1 (Receptor-Interacting Serine/Threonine-Protein Kinase 1) gene that impairs caspase-8-mediated cleavage. The result of this leads to uncontrolled activation of the RIPK1 kinase activity ultimately causing systemic inflammation. Immunologists, rheumatologists and genetic experts are the main doctors who can diagnose/identify it.
CRIA syndrome is caused by genetics. It is diagnosed using clinical features, blood work and screening for the genetic mutation. There are common mutations associated with this disease that prevent RIPK1 from being cleaved at Asp324, leading to excessive kinase activity. Under normal conditions, caspase-8 cleaves RIPK1 to block necroptosis and reduce inflammation. In CRIA syndrome, cleavage-resistant RIPK1 builds up and becomes hyperactive, triggering many symptoms that mimic autoimmune diseases and other chronic illnesses. CRIA syndrome triggers necroptosis (programmed inflammatory cell death), increased cytokine release, especially IL-6, and TNF and systemic and organ-specific inflammation. CRIA syndrome attacks joints, the eyes, muscles, the immune and inflammatory system, the neurological system, the gastrointestinal system, the lymphatic system, the hepatosplenic system, blood, the skin system and much more.