According to researchers, a protein called sulfatase-2 has been identified that plays a crucial role in damage because of rheumatoid arthritis. Rheumatoid arthritis is a disease of the immune system, where it attacks the joint tissues of the body. It affects an estimated 1.5 million people in the United States.
The study was published in the journal Cellular and Molecular Immunology and has shed light on molecular processes driving inflammation seen in RA. Furthermore, it can also improve the treatment of RA, which does not have a cure currently.
Professor Washington State University’s College of Pharmacy and Pharmaceutical Sciences, senior author Salah-Uddin Ahmed said,
Tumour 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
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 signalling, so basically, proteins that it interacts with that may play a role.
Ahmed also said that although sulfates have been studied thoroughly for cancers, no one looked at them as a causative factor of inflammatory autoimmune diseases. For example, rheumatoid arthritis.
The idea was explored by the research team through synovial fibroblasts.
Author Ruby J. Siegel said,
In rheumatoid arthritis, these normally quiescent cells get activated by TNF-alpha and other inflammatory molecules, and they take on this aggressive character
They are not dying when they should, and they proliferate in a way that is almost tumour-like, forming this massive synovial tissue that should not be anywhere near that size and at the same time activating proteins that destroy cartilage and bone.
Inflammatory Response of Sulfatase-2
The researchers removed sulfatase 2 from a group of cells with inflammatory TNF alpha. They used the cells lining the joints of rheumatoid arthritis to do so. Researchers discovered that the cells which lacked sulfatase 2 had no exaggerated inflammatory response to the intact TNF alpha cells.
Ahmed said,
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
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 experiments were done over a span of four years. Eventually, the researchers found a new path to future animal studies testing the effectiveness of inhibiting sulfate for easing the symptoms of rheumatoid arthritis. Furthermore, it can also help develop new experiments, which will allow using a combination of therapies to treat or prevent various conditions. For example, bone loss prevention, prevention of cartilage damage and joint deformation. Additionally, it can also address shortcomings of the RA drugs currently available in the market. Most of which have significant side effects.
Seigel said that patients taking these drugs are susceptible to infection and increased cancer risk when used over a long period. Moreover, she also noted that TNF alpha inhibitors are prohibited in patients with certain health problems.
These drugs shut off TNF-alpha in your whole body, but it does have important immune functions
