Exploring Root Causes and Developing New Treatments for Ankylosing Spondylitis

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Ankylosing spondylitis (AS) is a form of arthritis that primarily affects the spine and joints, but patients often experience inflammation in other parts of the body, particularly the eyes. Dr. James Rosenbaum, at Good Samaritan Foundation, 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, inflammation, and the microbiome.

To differentiate between autoimmune and immune diseases, Rosenbaum offers an example: rheumatoid arthritis is autoimmune because the body’s immune system mistakenly targets something produced by the body itself. In contrast, gluten sensitivity is not autoimmune 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 antibodies, 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 autoimmune, auto-inflammatory, or immune without being autoimmune.”

Previous research has shown that HLA-B27, a gene commonly found in arthritis 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 arthritis, 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 autoimmune 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 believes 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.