in The ANRF Chronicle
July is Juvenile Arthritis (JA) month. ANRF has a long history of supporting JA research and wanted to share past, present and future researchers’ work who have used their ANRF research grant to take up the fight against this childhood condition.
Dr. Scott Canna: JIA a Weapon of MAS destruction
ANRF scholar 2013-2014
Macrophage Activation Syndrome (MAS) is a life-threatening complication of systemic juvenile idiopathic arthritis, which results in the rapid onset of severe systemic inflammation. As an ANRF scholar, Dr Canna identified a gene mutation that affects inflammasomes, which are sensors in the innate immune system that respond to pathogens and damage by inducing inflammation. This mutation causes recurrent fever flares and MAS. This research offered potential new targets to treat this secondary condition. Dr Canna is now Assistant Professor of Pediatrics at the Children’s Hospital of Philadelphia and runs the Canna laboratory at the Perelman School of Medicine, University of Pennsylvania. In his lab he continues to carry out thought provoking and necessary research in autoinflammation and hyperinflammation and how these two processes interact, including building on his work as an ANRF scholar by examining the mechanisms driving MAS and testing promising therapeutic strategies.
Michael Waterfield: Storm Trooper Training
ANRF scholar 2019-2020
One ANRF researcher that geared up to fight JIA is Dr Michael Waterfield, a pediatric rheumatologist at UCSF Benioff Children’s Hospital in San Francisco. The aggressive inflammation that frequently accompanies JIA can lead to impaired growth and on-going joint problems. In around 50% of cases, this will persist throughout a patient’s life. T-cells are the storm troopers that our body unleashes in order to fight disease-causing molecules. One such T cell, T-helper 17 (Th17), is seen in large numbers in patients with autoimmune conditions, including those with JIA. Inhibiting Th17 is increasing in use as a therapeutic tool against these conditions. In order to fully utilize this approach it is necessary to understand how Th17 drives inflammation. The ANRF grant allowed Dr Waterfield to identify a molecule (ATF7ip) which regulates Th17. Currently, he and his team are studying the mechanisms ATF7ip uses to impact Th17 cells and whether this can be utilized to control them in a way that reduces inflammation.
Dr. Lauren Henderson: A Case of Mistaken Identity
ANRF scholar 2020-2021 & 2021-2022
Our immune systems need to identify cells which are our own and those which are foreign. A special type of immune cell, regulatory T cells, help our bodies to know which are which. They act like scouts in the army identifying when a foreign army is on the attack. Sometimes these regulatory T cells make mistakes, thinking that our own cells are foreign invaders that need to be delt with accordingly. Dr Henderson hopes to identify why this happens in oligo JIA patients and if there is a way to help these T cells to better recognize our own cells as belonging to our own army to prevent unnecessary attacks on them. Based on the work she did in her first year as an ANRF scholar, which generated promising data she has been awarded a second year of funding. “As a pediatric rheumatologist, I care for a large number of children with JIA. I would like to better understand JIA so I can take better care of my patients. It is important to discover what pathways are driving this disease so new treatments can be developed.”
Pui Y Lee: Cells playing broken telephone
ANRF Scholar 2021-2022
Our cells talk to each other in order to ensure they’re on the same page in how they respond to what the body needs. Occasionally wires get crossed and one cell doesn’t understand what the other is saying, a bit like playing broken telephone as a child. Inflammation is a necessary protective response by cells to prevent further injury or damage. In children with sJIA it seems that some cells are constantly shouting for help even when it is no longer needed, leading to excessive inflammation. Dr Lee hopes to determine which cells in sJIA children won’t stop talking. Medications that help these cells to realize they no longer need to shout already exist, so it is possible a new sJIA medication could be feasible in a short time frame.
We are incredibly proud of the research and researchers we fund each year. This is not possible without the astonishing support we receive from our donors. To support JA research through the ANRF please visit us here: https://curearthritis.org/donation/