A team led by researchers at the University of Birmingham in the United Kingdom recently discovered that two specific cytokines are mainly expressed in the early stage of rheumatoid arthritis (RA) disease. The study is entitled “Expression of chemokines CXCL4 and CXCL7 by synovial macrophages defines an early stage of rheumatoid arthritis” and was published in the journal Annals of Rheumatic Disease.
RA is an autoimmune disease that leads to chronic inflammation of the joints and other parts of the body due to an overreaction of the body’s own immune system, resulting in the attack of healthy tissues. In the United States, it is estimated that about 1.5 million people suffer from the disease, with women having a significantly higher susceptibility. The diagnosis of the disease at an early stage is usually linked to a better prognosis.
Inflammation of the synovium (lining of the joints) in RA patients has been reported to be associated to a complex inflammatory infiltrate involving cytokines, small signaling molecules that help to mount an immune response. In the study, the research team analyzed the expression of several cytokines in patients with very early arthritis (early stages of synovial inflammation).
The research team obtained synovial biopsies from patients in the Birmingham Early Arthritis Cohort (BEACON) study in the United Kingdom, who had at least one new swollen joint within 12 weeks of symptom onset. As controls, biopsies were also obtained from RA patients with longer symptom duration (more than 12 weeks) and individuals with no clinically apparent inflammation. At an 18-month follow-up visit, patients whose arthritis had resolved and patients who developed RA were identified.
Researchers analyzed synovial mRNA expression of 117 different cytokines and found that the cytokines CXCL4 and CXCL7 had a significantly higher expression in patients with early RA in comparison to controls without inflammation. Higher levels of CXCL4 and CXCL7 proteins were also found in early RA patients compared to the ones with resolving arthritis or a longer established RA. The two cytokines were predominantly detected on macrophages (a type of white blood cell that contributes to inflammation) infiltrating in the synovial fluid, suggesting that this cell type might play a previously unknown role in early RA pathogenesis.
The research team concluded that two cytokines, CXCL4 and CXCL7, are expressed in the synovium in the earliest clinically apparent stage of RA. Researchers hypothesized that these cytokines might exacerbate synovial inflammation in RA patients and promote its chronicity.