Rheumatoid Arthritis Pain, Degradation Stems from Single Receptor

Researchers found a single receptor that appears to aggravate RA symptoms.

Activating a single receptor located in the cells of arthritic joint fluid provokes the pain and joint degradation associated with rheumatoid arthritis, research from the University of Illinois at Chicago College of Medicine suggests.

The study was published online September 8, 2014, in the Journal of Immunology.

Researchers found a greater amount of toll-like receptor 5 (TLR5), a myeloid cell normally found in the blood, in participants with rheumatoid arthritis joint fluid than they found in fluid samples from healthy controls. The receptor increases tumor necrosis factor alpha levels, which attract more myeloid cells to the joint. Once in the joint, the myeloid cells are turned into bone-degrading cells.

“TLR5 does it all,” Shiva Shahrara, corresponding author and Associate Professor of Rheumatology at the school, said in a press release. “When TLR5 is activated, it initiates a vicious feedback loop that results in a worsening of both the inflammatory and erosive features of rheumatoid arthritis.”

The study builds on Dr. Shahrara and her research team’s prior findings, which determined that TLR5 activation resulted in abnormal blood vessel formation in the joints of rheumatoid arthritis patients.

Their latest research determined that toll-like receptor 5 expressing myeloid cells migrated to joint fluid from rheumatoid arthritis patients. When an antibody blocked the receptor, cell migration lowered significantly, the authors noted.

Researchers also found higher tumor necrosis factor alpha levels in the joint fluid if myeloid cells with activated toll-like receptor 5 were present, which could explain the efficacy of anti-tumor necrosis factor alpha therapies.

An antibody blocking toll-like receptor 5 reduced joint swelling and bone erosion in a mouse model, the study showed. It may additionally lower the number of cells migrating to joints to become bone-eroding tissue, they added.

“The receptor is a major driver of inflammation and bone degradation,” Dr. Shahrara said. “Blocking this receptor could have significant therapeutic value in interrupting joint swelling and bone loss in patients with rheumatoid arthritis.”