Ankylosing spondylitis (AS) is a form of arthritisArthritis is the swelling and tenderness of one or more joints. Learn more. that primarily affects the spine and joints, but patients often experience inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when... in other parts of the body, particularly the eyes. Dr. James Rosenbaum, Senior Vice President of Research at Corvus Pharmaceuticals, is working to uncover the underlying causes of AS and develop new treatments.
“We don’t know exactly what provokes the immune system in ankylosing spondylitis, and it’s also a mystery why the eye is involved in a disease that primarily affects the joints,” says Rosenbaum. “My project aims to better understand this connection and the root cause of the disease.”
Rosenbaum explains that while the study of the microbiome—the community of bacteria living in our bodies—is relatively new, it is central to his research. He and his colleagues are particularly interested in the relationship between bacterial products, inflammationInflammation is a normal part of the body’s defense to injury or infection, and, in this way, it is beneficial. But inflammation is damaging when..., and the microbiome.
To differentiate between autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... and immune diseases, Rosenbaum offers an example: rheumatoid arthritisThe most common autoimmune type of arthritis. In RA, your body’s immune system begins to react against its own tissues, causing significant inflammation in your... is autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... because the body’s immune system mistakenly targets something produced by the body itself. In contrast, gluten sensitivity is not autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... because the immune response targets something external, like gluten.
“We have an adaptive immune system and an innate immune system,” Rosenbaum explains. “The adaptive immune system involves antibodiesAntibodies are proteins that protect you when an unwanted substance enters your body. Produced by your immune system, antibodies bind to these unwanted substances in..., T lymphocytes, and B lymphocytes, and is highly specific—like a guided missile—but it takes a few days to learn and target the threat. On the other hand, the innate immune system is less specific but responds more quickly. The key question with ankylosing spondylitis is whether it is autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents...., auto-inflammatory, or immune without being autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.....”
Previous research has shown that HLA-B27, a gene commonly found in arthritisArthritis is the swelling and tenderness of one or more joints. Learn more. patients, plays a crucial role in AS. To explore this connection, researchers in Dallas created transgenic rats with the HLA-B27 gene. These rats developed symptoms similar to AS, but when raised in a germ-free environment, they showed minimal or no arthritisArthritis is the swelling and tenderness of one or more joints. Learn more. , suggesting that the microbiome plays a significant role in the disease’s development.
Collaborative efforts from researchers at Stanford University, Washington University, and Moscow have also made significant strides in understanding AS. They analyzed fluid from patients’ inflamed eyes and joints, finding that both body-derived and gut bacteria-derived antigens were involved. This discovery suggests that AS may have both autoimmuneAny disorder in which loss of function or destruction of normal tissue arises from humoral or cellular immune responses to the body’s own tissue constituents.... and bacterial components.
Looking ahead, researchers hope to develop new treatments for AS that work similarly to those used for managing peanut allergies. These treatments might involve early exposure to triggers or engineering gut bacteria to remove harmful antigens.
While many questions remain, Rosenbaum believe this research marks a significant step forward in solving a 50-year-old puzzle. He calls the Foundation “a godsend” for his research.
“I’ve been very privileged to receive the Foundation’s Innovative Research Award twice, and it has been immensely helpful in advancing my research, enabling publication, and training others,” says Rosenbaum.