Identifying Inflammatory Mechanisms in Rheumatoid Arthritis

The understanding of the inflammatory processes contributing to rheumatoid arthritis continues to grow, leading to greater understanding of RA and improved diagnostic tools and medications.

The understanding of the inflammatory processes contributing to rheumatoid arthritis (RA) continues to grow, leading to greater understanding of RA and improved diagnostic tools and medications. Now, researchers are zeroing in on the relationship between the presence of anti-citrullinated cyclic peptide antibodies (anti-CCP) and rheumatoid factor (RF) and their impact on the severity of RA.

Research has shown that the inflammatory process seems to begin with the recognition of arthritogenic antigens by CD4 + T helper (Th) lymphocytes, followed by macrophage and fibroblast stimulation. The inflammatory process is driven by cytokine production by these cells and Th17, and in severe cases of RA, regulatory T cells simply may not work as well as they should, possibly due to impaired production of interleukin (IL)-10 and transforming growth factor (TGF)-β.

A new study in BMC Musculoskeletal Disorders looked at citrullinated antibodies that enter the joints and promote local inflammation and tissue destruction and the potential role of phagocytes that release cytokines and reactive oxygen species (ROS). As yet, there is no consensus on the mechanisms by which anti-CCP and RF influence the pathogenesis of the disease, and the clinical evidence is split on whether phagocytosis is increased, decreased, or not significantly different at all in neutrophils of RA patients compared to those of healthy individuals.

The study compared phagocytic capacity and ROS production between patients with RA and healthy individuals and the phagocytic capacity and ROS production between subsets of patients who were positive or negative for anti-CCP or RF, and found increased phagocytosis by neutrophils in RA patients who were positive for anti-CCP and RF autoantibodies.

The study followed a cohort of 30 RA patients followed from early stages of the disease were characterized by positivity for RF or anti-CCP. Phagocytic capacity against Saccharomyces cerevisiae and superoxide anion production were assessed in RA patients and compared with 20 healthy controls. Phagocytic capacity and superoxide anion production were also compared between RF- and anti-CCP-positive and -negative RA patients.

The study authors note, “…neutrophils and monocytes from RA patients presented overall higher phagocytic capacity than neutrophils and monocytes from healthy controls (p&thinsp;<&thinsp;0.05). Furthermore, RA patients also showed a higher capacity for producing cytotoxic oxygen radicals (p&thinsp;=&thinsp;0.0026).”

The researchers acknowledge that the study conflicts with other research (although it mirrors other studies as well) and adds to the complexity of the pathophysiological interactions between phagocytes and autoantibodies. But they suggest that anti-CCP and RF may indirectly enhance the inflammation cascade involving neutrophils and may indirectly sustain tissue damage in RA. “Targeting the production of these autoantibodies may be a promising strategy in the management of RA,” the study authors conclude.