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). This "back-door" pathway can amplify inflammation even when the primary TNF pathway is blocked by current medications, shedding light on why up to 40% of rheumatoid arthritis patients don't respond to TNF-inhibiting drugs. The findings suggest new avenues for developing improved treatments for this debilitating autoimmune disease.

Why it matters

Rheumatoid arthritis affects roughly 1% of the world's population, causing painful joint inflammation and damage. While TNF-inhibiting drugs have provided relief for many patients, a significant portion still do not respond to these treatments. This discovery of an alternate inflammatory pathway mediated by TWEAK and Fn14 could lead to new combination therapies or drugs targeting this "back-door" route to better help those patients who don't respond to current medications.

The details

The research team, led by Salah-uddin Ahmed at Washington State University, found that the TWEAK and Fn14 proteins team up with TNF to amplify the inflammatory response in rheumatoid arthritis. When both the TNF pathway and the TWEAK/Fn14 pathway are active, inflammation surges. But when the Fn14 receptor-mediated pathway is blocked, the TNF-driven inflammation is dramatically reduced. This "crosstalk" between the two inflammatory pathways was previously unknown, providing a new potential target for therapies.

  • The findings were published in the journal Cellular & Molecular Immunology in January 2026.

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 the corresponding author of the new publication.

Farheen Shaikh

A former graduate student in Ahmed's lab who was the first author on the paper.

Washington State University

The university where the research was conducted.

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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 and Associate Dean for Research and Graduate Education

What’s next

Ahmed now plans to investigate potential therapeutics that would target both the TNF and TWEAK/Fn14 inflammatory pathways, as well as focus on the Fn14 path specifically. 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 an alternate inflammatory pathway mediated by TWEAK and Fn14 proteins provides a promising new avenue for improving treatments for the millions of people suffering from rheumatoid arthritis worldwide, particularly those who do not respond to current TNF-inhibiting medications.