Identification of the key protein responsible for the damage caused by rheumatoid arthritis: study | Health

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Scientists have identified a protein known as sulfatase-2 that plays a critical role in the damage caused by rheumatoid arthritis. The researchers’ discovery sheds new light on the molecular processes behind the inflammation seen in rheumatoid arthritis. It could also one day lead to improved treatment for the disease, which is currently incurable. (Also read: Physiotherapy tips for patients with osteoarthritis)


Published in the journal Cellular & Molecular Immunology, this finding sheds new light on the molecular processes behind the inflammation observed in rheumatoid arthritis. It could also one day lead to improved treatment for the disease, which is currently incurable.

“Tumor necrosis factor alpha – or TNF-alpha for short – is one of the key inflammatory proteins that cause rheumatoid arthritis and is targeted by many currently available therapies,” said lead author Salah- Uddin Ahmed, a professor in Washington State. University College of Pharmacy and Pharmaceutical Sciences. “However, over time patients can develop resistance to these drugs, which means they no longer work for them. Therefore, we were looking for previously unknown drug targets in TNF-alpha signaling, so the proteins it interacts with may play a role. “


Although sulfatases such as sulfatase-2 have been widely studied for their roles in different types of cancer, Ahmed said no one has looked into how they might be involved in inflammatory or autoimmune diseases such as rheumatoid arthritis. .

The research team first explored this idea using cells called synovial fibroblasts, which line the joints and keep them lubricated to ensure smooth movement.

“In rheumatoid arthritis, these normally quiescent cells are activated by TNF-alpha and other inflammatory molecules, and they take on this aggressive character,” said first author Ruby J. Siegel, a WSU Ph.D. College of Pharmacy and Pharmaceutical Sciences. “They don’t die when they should, and they proliferate in a way that’s almost tumor-like, forming this massive synovial tissue that shouldn’t be anywhere near that size and at the same time activating proteins that destroy cartilage and bones.”


Using joint lining cells from rheumatoid arthritis patients, they removed sulfatase-2 from a group of cells before stimulating all cells with the inflammatory TNF-alpha. What they found was that cells lacking sulfatase-2 did not show the same exaggerated inflammatory response to TNF-alpha as cells that remained intact.

“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 across different tissues. and samples that 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.”

Resulting from a series of experiments spanning four years, the researchers’ findings open the door to future animal studies to test the effectiveness of sulfatase-2 inhibition in relieving symptoms of rheumatoid arthritis. This could one day lead to the development of new combination therapies that, along with other inflammatory proteins, would also target sulfatase-2 to prevent bone loss, cartilage damage and deformed joints. Such therapies could help fill the gaps in currently available rheumatoid arthritis drugs, many of which come with significant side effects.


“These drugs block TNF-alpha throughout your body, but it has important immune functions,” Siegel said, adding that patients taking these types of drugs are more susceptible to infections and have an increased risk of developing cancer. long-term. use of the term. She also noted that TNF-alpha inhibitors are not effective for everyone and are not recommended for patients with certain other health conditions.

This story was published from a news feed with no text edits. Only the title has been changed.

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