The synovium in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic autoimmune disease targeting multiple joints. The synovium is the primary site of the inflammatory process, which if untreated leads to irreversible damage to the adjacent cartilage and bone. It is now well established that autoantibodies that are characteristic of RA, including rheumatoid factor (RF) and anti-citrulluninated protein antibodies (ACPA), are present before clinical disease onset. Studies in both humans and animal models are beginning to provide new insights into how this asymptomatic autoimmunity evolves into an inflammatory process that is localized in the synovium.Once RA synovitis established, a number of amplification mechanisms serve to sustain the process leading to the persistence of the disease. These mechanisms include engagement of the resident mesenchymal cells and the establishment of ectopic lymphoid structures in the synovium, although the relationship between these lymphoid structures and the presence of RA autoantibodies remains unclear.An enhanced understanding of the mechanisms that initiate and sustain RA synovitis offers unprecedented opportunities for therapeutics, and ultimately prevention strategies.

Keywords: Rheumatoid; innate; lymphoid neogenesis.; synovium.

Fig. (1)

Synovial tissue analysis of biopsy material obtained from a symptomatic knee joint shortly after onset of articular symptoms. A) H&E light microscopy showing marked disruption of the synovial lining cell layer. The lining cells appear to be floating in an amorphous extra-cellular matrix. The sublining stroma is relatively unremarkable with minimal evidence of inflammatory infiltration. B) Intracellular citrullinated antigens are detected by intense staining of the synovial lining cells using a polyclonal anti-citrulline antibody. There is less intense staining of the surrounding matrix. C) Immunofluoresence staining of synovial tissue for C3 showing positive staining in the lining layer. Similar results were seen with IgG, IgA, and fibrin staining. D) The synovial lining cells exhibit evidence for widespread apoptosis as detected by TUNEL staining. Original magnification x 200 for A), and x 400 for B), C), D).

Fig. (2)

Histopathology of RA synovitis. (A) lymphoid aggregate; (B) Diffuse lymphocytes infiltrate; (C) Hyperplasia of the lining layer; (D) Fibrin cap replacing a denuded lining layer.

Fig. (3)

Interface between pannus tissue and bone in a patient with RA. (A) the synovial lesion is invading the adjacent bone. (B) Staining for tartrate resistant acid phosphatase in the circled area demonstrates the presence of osteoclasts.

Fig. (4)

Conceptual framework for the evolution of RA synovitis.