UC San Diego: Study identifies key players in rheumatoid arthritis
University of California San Diego School of Medicine announced Monday that scientists have determined the cellular players and roles involved in rheumatoid arthritis, which affects over 1 million Americans.
Scientists used a "novel systems biology approach" to study the complex disease, which has defied a uniform set of treatments, according to a news release.
Published in the Oct, 20 issue of "Nature Communications," the research shows "that the same molecules involved in rheumatoid arthritis (RA) can have opposite functions in cells obtained from different patients — and help explain why current targeted therapies evoke different responses in patients with the same diagnosis and similar symptoms," according to UC San Diego.
System biology studies the interactions and behavior of all components of a biological entity.
According to the study authors, "The findings could help pave the way toward a greater understanding of RA's heterogeneity while providing better focus on existing and future therapies personalized to individual patients."
Arthritis encompasses more than 100 conditions affecting the joints, tissues around them and other connective tissues. An estimated 58 million-plus adults in the United States, or one in five, are living with the condition.
The most common form is osteoarthritis, which causes degeneration of the joints, often in hands, hips and knees. While RA might be less common, it affects over 2 million Americans, principally women.
RA is a systemic autoimmune disease that causes long-lasting or chronic, painful tissue inflammation in joints and can also harm other organs, such as the eyes, heart or lungs.
According to UC San Diego, there are many RA causes and risk factors that are not well understood involving age, inherited traits, obesity and lifestyle habits such as smoking.
While there iso cure for RA, targeted treatments are available to help slow disease progression, prevent joint deformity and reduce pain and disability.
"Although RA arises with similar clinical appearance between patients, response to any individual treatment is unpredictable and requires a trial and error method," said co-author Gary Firestein, a director of the Altman Clinical and Translational Research Institute at UC San Diego School of Medicine.
"This process is repeated until a drug that decreases disease activity for that particular patient is identified," Firestein said. "Many patients have improved outcomes, but a significant percentage do not. They have persistent inflammation. These variable responses to therapy indicate the same disease can have diverse mechanisms."
UC San Diego researchers in the study focused on fibroblast-like synoviocytes, a specialized cell type found inside joint synovium, or soft connective tissue, that lubricates joints and minimizes wear-and-tear. Those synoviocytes also contribute to RA joint destruction.
Researchers identified specific factors, including proteins that regulate the transcription or copying of genes, involved in individual RA patients' cell lines. In turn, the findings "allowed scientists to stratify those cell lines into at least two subtypes with different predicted activated pathways that could contribute to inflammation," according to UC San Diego.
"Essentially, we biologically validated these predictions for the top subtype-specific transcription factors," said co- author Wei Wang, a UC San Diego professor of biochemistry, chemistry, and cellular and molecular medicine. "This study is the first to characterize groups of cell lines from RA patients with distinctive transcription factor biology by integrating transcriptomic and epigenomic data."
Other study authors were Richard I. Ainsworth, Deepa Hammaker, Gyrid Nygaard, Cecilia Ansalone, Camilla Machado, Kai Zhang, Lina Zheng, Lucy Carrillo, Andre Wildberg, Amanda Kuhs and David L. Boyle, of UC San Diego; and Mattias N.D. Svensson, La Jolla Institute for Allergy and Immunology and the University of Gothenburg, Sweden.