An essential immune response regulator in both health and disease, the LYN gene, has been linked to an autoinflammatory disease. The discovery, known as Lyn kinase-associated vasculopathy and liver fibrosis (LAVLI), clarifies how genes connected to certain disorders may be possible targets for treatment by repurposing current medications. Adriana A. de Jesus, M.D., Ph.D., and Raphaela Goldbach-Mansky, M.D., M.H.S., of the Translational Autoinflammatory Diseases Section of the Laboratory of Clinical Immunology and Microbiology at the National Institute of Allergy and Infectious Diseases (NIAID), a component of the National Institutes of Health, led the study, which was published in Nature Communications.
Genetic testing that identified a mutation in the LYN gene, which codes for the Lyn kinase protein, led to the initial identification of LAVLI in a child patient. Later, it was found that the same gene had two more mutations in two unrelated pediatric patients. Shortly after birth, the three patients all experienced the onset of disorders connected to the LYN genetic mutation. In the first year of life, two patients experienced the onset of liver fibrosis (large amounts of scar tissue brought on by inflammation and repetitive liver damage).
All three patients developed neutrophilic cutaneous small vessel vasculitis that started during pregnancy. This immune condition is characterized by inflammation brought on by large numbers of neutrophils, which are immune system’s white blood cells that can harm small blood vessels.
The study revealed Lyn kinase was always active and unable to shut down in the three patients with the LYN mutation, which increased neutrophil migration, altered inflammatory signals and activated scar and fibrosis-inducing liver cells. The results of this study suggest that Lyn kinase may be a potential therapeutic target for drugs that treat forms of non-syndromic small vessel vasculitis and other types of inflammation-induced liver fibrosis.