Even for seasoned veterans, it can sometimes be difficult to fully appreciate the degree of rheumatoid disease activity based solely on the physical examination. One might examine the patient meticulously and not see much disease activity, yet the erythrocyte sedimentation rate and C-reactive protein levels may be elevated, or the Vectra scores may be high, suggesting that the patient has more disease activity than was seen on examination. Reliable imaging tools can help augment the history and physical examination, and some rheumatology practices have musculoskeletal ultrasound available to use toward this end.

Positron emission tomography (PET) imaging is of research interest in rheumatology, since it is an expensive test that is not likely to be covered by payers. However, findings from the present PET study by Narayan and colleagues are fascinating and potentially applicable to our understanding of RA pathophysiology. These investigators sought to better ascertain the cellular contributions to positive findings in TSPO PET imaging of the RA joint. Past work using a first-generation TSPO radioligand had suggested that TSPO PET could detect and quantify joint inflammation even at low levels, including subclinical synovitis. It had been assumed that PET findings in the synovium reflected TSPO expression by activated macrophages only.

The present study, which uses a next-generation TSPO radioligand, found that all of the cells known to be important in the RA pannus express TSPO, including macrophages, fibroblast-like synoviocytes, and T cells. Activated fibroblast-like synoviocytes, in particular, made high-level contributions to the TSPO PET signal, which may parallel the importance of these cells in the RA pannus. Indeed, the fibroblast-like synoviocyte is critical in driving inflammation and joint damage in patients with RA. These cells are activated by tumor necrosis factor and interleukin 1 beta (IL-1β), in addition to IL-17 and the important pro-inflammatory cytokine IL-6. When activated, the fibroblast-like synoviocyte becomes invasive and produces more IL-6, in a positive feedback loop. This cell also produces matrix metalloproteinases that erode cartilage and receptor activated nuclear factor-κΒ (RANK) ligand, which stimulates osteoclasts that are involved in bone erosion.

Thus, TSPO PET radioligand binding in RA joints appears to reflect the cellularity and activation of inflammatory cells within the RA pannus. The fact that TSPO PET detects all major cell groups in the RA, not just macrophages, suggests that it has the potential to be highly sensitive as an imaging technique.