New Pathway Discovered for Improving Rheumatoid Arthritis Treatment

Research finds TWEAK and Fn14 signaling amplify inflammation, offering potential new therapeutic targets

Published on Jan. 30, 2026

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Researchers at Washington State University have discovered a new inflammatory pathway involving the proteins TWEAK and Fn14 that works alongside the main inflammatory driver in rheumatoid arthritis, Tumor Necrosis Factor (TNF). The findings suggest blocking this alternate "backdoor" pathway could improve treatment for the roughly 30-40% of rheumatoid arthritis patients who don't respond to current TNF-inhibiting drugs.

Why it matters

Rheumatoid arthritis is a debilitating autoimmune disease affecting around 1% of the global population. While TNF-inhibiting drugs have been a major breakthrough, they don't work for a significant portion of patients. This new research uncovers an additional inflammatory mechanism that could lead to better treatments for those not helped by current medications.

The details

The study, published in Cellular & Molecular Immunology, found that TWEAK and its receptor Fn14 team up with TNF to amplify inflammation. When both the TNF and Fn14-mediated pathways are active, inflammation surges. But blocking the Fn14 receptor-mediated pathway can dramatically quiet the TNF-driven inflammatory response, suggesting it acts as an alternate "backdoor" route for inflammation.

  • The research was led by Salah-uddin Ahmed, a professor at Washington State University, and grew out of several years of work by former graduate student Farheen Shaikh, the paper's first author.

The players

Salah-uddin Ahmed

Professor and associate dean for research and graduate education in the College of Pharmacy and Pharmaceutical Sciences at Washington State University, and corresponding author of the new publication.

Farheen Shaikh

Former graduate student in Ahmed's lab and first author on the research paper.

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What they’re saying

“It's kind of like a back-door entry or an alternate route. If you shut the main door for TNF, it has other ways to cause inflammation.”

— Salah-uddin Ahmed, Professor (Mirage News)

What’s next

Ahmed now plans to investigate pathways for developing potential therapeutics, including targeting the two inflammatory pathways together or focusing specifically on the Fn14 path. Given the role of TNF in other autoimmune diseases, further study of the Fn14 function could also shed light on other illnesses.

The takeaway

This discovery of a secondary inflammatory pathway involving TWEAK and Fn14 signaling could lead to new treatment approaches for the significant portion of rheumatoid arthritis patients who don't respond to current TNF-inhibiting drugs, potentially helping millions suffering from this debilitating autoimmune disease.