By SPC News Staff
A new study proposes a better understanding of the site of inflammation in rheumatoid arthritis (RA), which may allow for the development of predictive biomarkers and possibly new personalized medicine approaches.
Because it is impossible to predict the disease’s course at diagnosis, clinicians use a trial-and-error approach to treatment, which could cause more joint damage before patients receive the best treatment for them.
A recent study by researchers at Trinity College Dublin and St. Vincent’s University Hospital, in Dublin, proposes a better understanding of the site of inflammation in RA (Sci Adv 2024;10[39]:eadj1252).
The team performed an in-depth investigation of the macrophages that reside in the synovium of RA patients, “individuals-at-risk” for RA and healthy controls. Researchers demonstrated the presence of a dominant macrophage subtype (CD40-expressing CD206+CD163+) in the inflamed RA synovium, which was associated with disease activity and treatment response.
These cells reside in the joints, which play a protective role in healthy bodies but become pro-inflammatory in disease, and release cytokines that induce inflammation, as well as activate the invasive fibroblast cell type, leading to cartilage and bone destruction. In parallel, the protective barrier macrophages (CX3CR1+) were depleted in established RA, showing a switch in the dominance of joint macrophages from protective macrophages to pro-inflammatory macrophages.
The researchers said they do not fully understand why this occurs.
They said the pro-inflammatory status of these macrophages is maintained by specific signaling and metabolic pathways within the joints, the targeting of which may induce resolution of inflammation. Of note, the team identified that these changes in the macrophage status occurred before the disease began.
Combined, these findings identify the presence of an early pathogenic macrophage cell/gene signature that shapes the RA joint inflammatory environment and represents a unique opportunity for early diagnosis and therapeutic intervention.
