Study Finds Novel Protein Response for Rheumatoid Arthritis Damage

Researchers of a new study have identified a novel protein that plays in a chief role in rheumatoid arthritis (RA). The protein, called sulfatase-2, drives inflammation in RA. The findings were published in Cellular & Molecular Immunology. 

Sulfatases have been previously studied for their role in cancer, but the protein’s role in inflammatory diseases like RA is less understood. The investigators analyzed the concept of using called synovial fibroblasts, which line the joints and keep them lubricated to ensure fluid movement. According to the study, they used the joint-lining cells of rheumatoid arthritis patients to remove sulfatase-2 from one group of cells before stimulating all cells with TNF-alpha.

“Tumor necrosis factor-alpha—or TNF-alpha for short—is one of the main inflammatory proteins that drive rheumatoid arthritis and is targeted by many currently available therapies,” said senior author Salah-Uddin Ahmed, a professor in Washington State University’s College of Pharmacy and Pharmaceutical Sciences via a press release. “However, over time patients can develop a resistance to these drugs, meaning they no longer work for them. That is why we were looking for previously undiscovered drug targets in TNF-alpha signaling, so basically proteins that it interacts with that may play a role.”

“Looking at sulfatases for their potential role in inflammation was an educated guess, but once we did we saw a very consistent pattern of increased sulfatase-2 expression throughout different tissues and samples we studied,” Ahmed said. “This tells us that TNF-alpha relies on sulfatase-2 to drive inflammation, because as soon as we removed sulfatase-2 the inflammatory effects of TNF-alpha were markedly reduced.”

The findings of this study could potentially lead to the development of novel therapies that inhibiting sulfatase-2 to ameliorate RA symptoms. “These drugs shut off TNF-alpha in your whole body, but it does have important immune functions.”