Second Finlay Herrington Award
The second award in memory of Finlay Herrington will fund Dr Francesca Sposito to pursue her research project entitled:
The Role Of IFIH1 loss-of-function variants in Juvenile-onset Systemic Lupus Erythematosus and Associated ImmuNodeficiency – TROJAN
Brief Project Summary
Systemic lupus erythematosus (SLE) is a rare autoimmune/inflammatory disease in which an overactive immune system causes inflammation and damage to organs. Children with SLE experience higher disease activity than adults, have greater organ damage and an even higher risk of death.
Though the precise cause of SLE is unknown, it is possible that mutations in certain genes result in patients developing the disease. These mutations might also increase patients’ susceptibility to viral infections.
The family of Finlay Herrington is supporting researchers at the University of Liverpool to study genes that help the body detect viruses. Epstein-Barr virus (EBV) infection is common in children before developing SLE, the research team will study how EBV virus may trigger autoimmune/inflammatory diseases hoping this may ultimately help develop new treatments for SLE and other diseases with increased risk of virus infections.
Detailed project summary
Contributing to earlier disease onset and increase severity, development of SLE during childhood is linked to a higher number of gene variants. Genes are the “blueprints” of our organs/body.
The research team investigated gene variants of 348 childhood SLE patients and identified previously not known variants in the IFIH1gene which switch it “off”. These IFIH1 variants were more than twice as common among children with SLE when compared to healthy controls. The IFIH1 gene comprises the “blueprints” for a receptor that detects viruses. Reduced receptor activity may therefore result in more severe and recurrent virus infections including Epstein-Barr virus (EBV).
This project will investigate SLE-associated IFIH1 variants that turn the gene “off”, because:
· Defects in fighting infections can cause uncontrolled inflammation and autoimmunity.
· Virus infections (especially EBV) are common among SLE patients, even before SLE develops.
Thus, the research team will generate immune and airway cells that carry childhood SLE-associated IFIH1 gene variants to investigate how they impact on virus infection risk and inflammation. They will infect genetically modified cells with EBV and measure virus counts as well as resulting inflammation and cell damage.
Dr Francesca Sposito completed her Bachelor’s Degree in Biological Sciences and Master’s Degree in Genetics and Molecular Biology at Sapienza University of Rome, Italy. During her PhD studies at the University of Liverpool she investigated molecular mechanisms protecting children from severe COVID-19. Based on this work, she moved her focus to investigating the contribution of virus infection as a trigger of systemic autoimmune /inflammatory disease. Dr Sposito is currently a Research Associate at the UK’s ‘Experimental Arthritis Treatment Centre for Children’, Department of Women and Children’s Health, University of Liverpool.
