Tamir Diamond, MD
Autoimmune Fund for the Cure Pilot Research Award
$50,000 over one year
Children's Hospital of Philadelphia
Immunophenotyping of Acute Fulminant Pediatric Autoimmune Hepatitis
Autoimmune hepatitis is a common cause of liver failure in children. The immune system attacks the liver, leading to liver failure and, in some cases, the need for a liver transplant. Diagnosis is usually straightforward as most patients have positive markers in standard labs, known as seropositive autoimmune hepatitis. These patients respond well to medications that have been on the market for many years. However, approximately 20% of patients with immune system damage to the liver do not have these markers in their labs. They are referred to as seronegative autoimmune hepatitis. This is a group that is more heterogenous, and recent studies showed that it includes patients who actually don't have autoimmune hepatitis. For instance, some seronegative autoimmune hepatitis patients also experience injury to their bone marrow, in addition to the liver while other patients don't need long term medication to suppress their immune system. These observations suggest that seronegative autoimmune hepatitis may have groups of patients with a different disease requiring a different treatment approach. Previous research we and others conducted defined one of these sub-groups as Pediatric Activated T-cell Hepatitis (TC-Hep). In this project, we aim to further understand the differences between pediatric seropositive autoimmune hepatitis, seronegative autoimmune hepatitis and TC-Hep. We will study archived biopsies from patients with seropositive autoimmune hepatitis, seronegative autoimmune hepatitis and TC-Hep. We will use spatial transcriptomics, a technology that allows us to examine which genes are activated in immune cells, how they interact with liver cells and how they differ between the three groups of disease. The results of this study will provide valuable insights into the biology of each disease and inform the development of better medications to prevent liver failure in children.