Blocking one receptor on cells could halt rheumatoid arthritis

Researchers at the University of Illinois at Chicago College of Medicine have shown for the first time how the activation of a receptor provokes the inflammation and bone degradation of rheumatoid arthritis — and that activation of this one receptor, found on cells in the fluid of arthritic joints, is all that is required.

Their findings, published in the Journal of Immunology, point to a new therapeutic target to interrupt the vicious cycle of inflammation and bone erosion in rheumatoid arthritis.

Rheumatoid arthritis is a progressive autoimmune inflammatory disease of the joints. Swelling and pain, caused by certain cells flooding into the joints, is a hallmark of the disease, along with progressive bone loss. The UIC researchers have shown that the process begins with the triggering of a single receptor on a group of white blood cells.

“TLR5 does it all,” says Shiva Shahrara, UIC associate professor of rheumatology and corresponding author on the paper. TLR5, or toll-like receptor 5, is found on myeloid, or marrow-derived, cells that migrate from the blood into affected joints. Shahrara and her colleagues found that the receptor is much more abundant on myeloid cells found in the fluid of joints in patients with rheumatoid arthritis as compared to samples from healthy subjects.

In previous studies, Shahrara and her colleagues found that activation of TLR5 causes abnormal blood vessel formation in the joints of rheumatoid arthritis patients. In the new study they found that the receptor also up-regulates a potent inflammatory molecule called TNF-alpha, which recruits even more myeloid cells into the joint, where they are transformed into bone-degrading cells called osteoclasts.

In a series of experiments, the researchers uncovered multiple pathological processes driven by the activation of the receptor.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of unknown cause. An external trigger (eg, cigarette smoking, infection, or trauma) that triggers an autoimmune reaction, leading to synovial hypertrophy and chronic joint inflammation along with the potential for extra-articular manifestations, is theorized to occur in genetically susceptible individuals.

Essential update: Parental history of substance addiction may increase likelihood of developing arthritis

In an analysis of data on 13,036 adults from the 2005 Canadian Community Health Survey, Fuller-Thomson and colleagues found that children who grew up with a drug- or alcohol-addicted parent were at significantly increased risk for developing arthritis in adulthood. After adjustment for demographic characteristics, socioeconomic status, adult health behaviors, mental health conditions, and adverse childhood experiences, the odds ratio for developing arthritis among subjects with an addicted parent was 1.30 (95% CI: 1.12 - 1.51).