Comparison of the nodule and synovial lesions of rheumatoid arthritis

We have undertaken a number of investigations of the rheumatoid nodule. The infiltrating cell populations are activated macrophages migrating centrally to the palisade, and a diffuse infiltrate of T cells that tend to cluster outside the palisade. In this area we have also demonstrated the presence of putative dendritic cells, suggesting the potential for presentation of local antigen within the nodule. Macrophages within the nodule stain positively for tumour necrosis factor and IL-1. We have recently used RT-PCR to demonstrate the presence of mRNA for INF-γ but not IL-4 or IL-5. Monokines included IL-12, IL-15 and IL-18 as well as tumour necrosis factor alpha and IL-1β. We interpreted this as best fitting a Th1 profile.

As well as similarities, there are significant differences between the nodule and the synovial lesions of rheumatoid arthritis. A notable difference is the lack of B cells and lymphoid follicles in the rheumatoid nodule. Thus, we were able to demonstrate expression of the follicular dendritic cell-specific gene CD 21L in synovial membranes but not in the nodule. However, the chemokine SLC was present in both lesions, as was BCA-1, despite the absence of B cells in the nodule. Similarly, lymphotoxin alpha and lymphotoxin beta, which are important in follicle formation, were present in both lesions. Expression of the SLC receptor CCR7 was rare, but an alternative receptor, CCBP2, was present in both lesions. CXCR5, the BCA-1 receptor expressed by B cells, was present in the synovium. Thus, expression of chemokines for B cells and key cytokines important to follicle formation are present in both the nodule and synovial membrane. Therefore, other differences must explain the lack of B cells and follicles in the nodule.

The data suggest that the destructive inflammatory processes in the nodule and the synovial membrane may be essentially similar T-cell-driven lesions. Discovering the basis of differences such as the lack of B cells and follicles in the nodule may help the definition of important aspects of the inflammatory process in rheumatoid arthritis.