What Triggers Juvenile Idiopathic Arthritis?

Researchers have suggested the protein transthyretin may cause an autoimmune reaction in the synovial fluid of patients with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) may be triggered by autoimmune responses, according to findings published in the journal JCI Insight.

Researchers from Albert Einstein College of Medicine and the Children’s Hospital at Montefiore identified the molecular chaperone transthyretin (TTR) in synovial fluids in JIA patients in order to determine which antigens stimulate the autoimmune response. TTR transports molecules like thyroxine and retinol (vitamin A) throughout the blood and spinal fluid. The researchers added that recent studies demonstrate TTR as one of the proteins upregulated by the synovial fluid in JIA patients, but the specific antigens have yet to be identified; plus, they said, onset of JIA might be caused when TTR pools in the joints.

The researchers looked for abnormal protein deposits in the synovial fluid and blood samples of JIA patients using mass spectrometry and other biophysical methods, a press release explained. They saw misfolded and aggregated TTR in the synovial fluids of JIA patients, as well as heavily oxidized TTR. The researchers also gave the abnormal TTR to experimental mice, which caused a higher immunogenic response compared to untreated mice.

The investigators found that TTR was increased in 50 JIA patients at Montefiore, but not in any of the 26 control patients without JIA. Some of the JIA patients had unusually high levels of TTR, the study authors reported, and noted that this needed further examination. Upon conducting such research, the team analyzed 43 other JIA patients and found similarly significant TTR auto antibody deposits in each of the patients.

“Our findings regarding TTR’s involvement in JIA point to a potential treatment — encouraging news for children with this debilitating disease,” study leader Laura Santambrogio, MD, PhD, explained in the statement.

Santambrogio continued by adding that JIA patients may benefit from a drug that targets TTR, called tafamidis, which is currently undergoing phase III trials in the United States. Tafamidis is approved in Europe and Japan for treatment of familial amyloidosis — another disease linked to TTR.

“The TTR protein has a tendency to misfold and then aggregate, which for some reason seems to occur in children with JIA,” said Santambrogio. “And when proteins aggregate, they tend to become more immunogenic.”