The goal of pharmacological treatment for rheumatoid arthritis (RA) is to achieve disease remission by preventing joint inflammation and progressive bone erosion. A recent study published in Frontiers in Immunology indicates that patients with progressive erosive disease exhibit abnormalities in B cells and cytokines that play a role in bone reabsorption.
The study, conducted by Marasco and colleagues, involved 20 RA patients and twelve healthy donors (HD). Out of the twenty RA patients, ten showed bone erosion (RA-BE+), while the other ten did not (RA-BE-). The researchers found a significant increase in the number of CXCR5- PD1+ T peripheral helper cells (Tph cells) in RA patients, along with a decrease in the number of total memory B cells and switched memory B cells compared to HD. The total number of B cells was also found to be higher in RA-BE+ patients compared to RA-BE- patients. When the researchers analyzed the cytokines, they found that HD patients were well separated from RA patients. However, the RA-BE+ patients were not well segregated from RA-BE- patients. The levels of IL-11 and IL-17A were significantly higher in RA-BE+ patients compared to RA-BE- patients.
B cells play a crucial role in the development of RA. They produce antibodies against citrullinated proteins, present antigens to T cells, and release pro-inflammatory cytokines. In RA, B cells enter the synovial membrane and accumulate in tertiary lymphoid tissues, where they are activated with the assistance of Tph cells and refine their antigen receptor in germinal center-like structures.
IL-17 comprises a group of pro-inflammatory mediators produced by Th17 cells. These cytokines are present in synovial joints and contribute to bone resorption, activation of fibroblast-like synoviocytes, and the recruitment and activation of neutrophils, macrophages, and B cells. IL-11, which belongs to the IL-6 family of cytokines, is also involved in inflammatory diseases like RA
The data from the present study suggests that abnormalities in B cells and cytokines with a proven role in bone reabsorption are characteristic of patients with progressive erosive disease in RA. By understanding the molecular mechanisms of B cells and the cytokines IL-11 and IL-17A involved in progressive erosive disease, it is possible to develop novel treatment approaches aimed at preventing joint damage and disability in RA patients. However, it is essential to note that further large cohort and clinical studies are necessary to validate the current findings.
Marasco E, Fabbriciani G, Rotunno L, Longhi M, De Luca P, de Girolamo L, et al. Identification of biomarkers in patients with rheumatoid arthritis responsive to DMARDs but with progressive bone erosion. Front Immunol. 2023 Sep 19;14:1254139.