Study identifies human protein that triggers Juvenile Arthritis
A new study, led by researchers at Albert Einstein College of Medicine and the Children’s Hospital at Montefiore (CHAM), has found evidence that a human protein called transthyretin (TTR) causes an autoimmune reaction in the joints of Juvenile idiopathic arthritis patients.
Juvenile idiopathic arthritis (JIA) is the most common form of childhood arthritis and appears to be an autoimmune disease, caused by antibodies attacking certain proteins in a person’s own tissue. It affects approx. 300,000 in the US and symptoms include chronic joint pain, swelling and stiffness, which may persist for a few months, or a lifetime.
Until now, no autoantigens, the proteins triggering immune attacked, have been linked to JIA, but this new study, published in JCI Insight, links TTR with JIA.
“Our findings regarding TTR’s involvement in JIA point to a potential treatment – encouraging news for children with this debilitating disease,” says Dr Laura Santambrogio, study leader and professor of pathology, of microbiology & immunology, and of orthopaedic surgery at Einstein.
She goes on to say that JIA patients may benefit from a drug called tafamidis, which targets TTR. Tafamidis was approved in Europe and Japan for treating familial amyloidosis, which is also linked to TTR. The drug is now undergoing phase III trials in the US.
For the current study, Dr Santambrogio and her team of researchers, looked for abnormal accumulations of proteins in the synovial fluid (which bathes the joints) and blood of patients with JIA. They found a significant increase in TTR in 50 patients at the Children’s Hospital at Montefiore, but not in any of the 26 control children who did not have JIA. Further analysis reveals that some JIA patients had unusually high levels of anitbodies to the TTR protein. The team validated this finding by analysing 43 other JIA patients and found a significant increase in TTR autoantibodies in all of them.
TTR is a molecule “chaperone” that transports various molecules in the blood and cerebral spinal fluid. The researchers suspect that JIA begins when TTR collects in the joints.
“The TTR protein has a tendency to misfold and then aggregate, which for some reason seems to occur in children with JIA,” says Dr Santambrogio. “And when proteins aggregate, they tend to become immunogenic.”
Treatments such as nonsteroidal anti-inflammatory drugs and biologic response modifiers are used to control symptoms and prevent complications in patients with JIA, although currently there is no cure.
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