Rheumatoid arthritis mechanisms may vary by joint

NIH | JULY 17, 2016

Rheumatoid arthritis is an autoimmune disease in which the immune system mistakenly attacks the body’s own tissue, such as the membranes that line joints. This can cause pain, swelling, stiffness, and loss of function in joints throughout the body. For unknown reasons, different joints are affected differently in people with rheumatoid arthritis.

Rheumatoid arthritis joint. Photo: NIAMS/NIH

The causes of rheumatoid arthritis aren’t completely understood. Several genes involved in the immune system have been associated with a tendency to develop rheumatoid arthritis. Environmental factors—such as cigarette smoking, diet, and stress—may also play a role in triggering the disease. A better understanding of the molecular mechanisms at work in the disease may lead to more effective approaches to treatment.

A research team from the University of California, San Diego, has been studying fibroblast-like synoviocytes (FLS), a type of cell that lines joints and contributes to joint destruction in rheumatoid arthritis.

In past work, the team gained insights into how these cells function using epigenetics—the study of factors that change the way genes are read, or expressed, without changing the DNA sequence itself. They identified patterns of DNA methylation—a common epigenetic modification that affects gene expression—in FLS that differ between rheumatoid arthritis and osteoarthritis.

The scientists used computer analyses to group the samples according to the thousands of methylation differences they found across the genome. As expected, methylation patterns differed between rheumatoid arthritis FLS and osteoarthritis FLS. The team found the patterns also differed between rheumatoid arthritis FLS isolated from knees and hips.

The researchers next examined the biological pathways affected and identified several in FLS that were differentially methylated between rheumatoid arthritis knees and hips. Gene expression analysis confirmed that genes and pathways differ between the joint locations. Many of these pathways are related to immune function and inflammation.

The team next examined drugs developed for use in rheumatoid arthritis. They compared the drugs’ targets to the joint-specific biological pathways they uncovered. This analysis suggested that several promising drugs might have been assessed differently if these pathways had been taken into account. This analytical method could form the basis for developing precision medicine approaches to rheumatoid arthritis.

YOU MAY ALSO LIKE

Study: Olive Oil Protects Brain From Alzheimer’s

The benefits of a Mediterranean diet are widely chronicled, but new research shows extra-virgin olive oil, a key part of the diet, may protect “against cognitive decline.”

No safe level of smoking: Even low-intensity smokers are at increased risk of earlier death

People who consistently smoked an average of less than one cigarette per day over their lifetime had a 64 percent higher risk of earlier death than never smokers, and those who smoked between one and 10 cigarettes a day had an 87 percent higher risk of earlier death than never smokers, according to a new study from researchers at the National Cancer Institute.

Oxytocin affects facial recognition

A genetic variation in the receptor for oxytocin, a hormone involved in social bonding, affects the ability to remember faces in families with a child who has autism. The finding points the way to a better understanding of oxytocin’s role in social behavior.

Anxiety May Be Alleviated by Changing Gut Bacteria

Anxiety may be alleviated by changing a person’s gut bacteria, new research suggests.

Scientists create ‘genetic atlas’ of proteins in human blood

An international team of researchers led by scientists at the University of Cambridge and MSD has created the first detailed genetic map of human proteins, the key building blocks of biology.

Study solves ovarian cell mystery, shedding new light on reproductive disorders

Scientists have solved a long-standing mystery about the origin of one of the cell types that make up the ovary. The team also discovered how ovarian cells share information during development of an ovarian follicle, which holds the maturing egg.