Objective. To investigate the pathologic nature of features termed "bone erosion" and "bone marrow edema" (also called "osteitis) on magnetic resonance imaging (MRI) scans of joints affected by rheumatoid arthritis (RA).Methods. RA patients scheduled for joint replacement surgery (metacarpophalangeal or proximal interphalangeal joints) underwent MRI on the day before surgery. The presence and localization of bone erosions and bone marrow edema as evidenced by MRI (MRI bone erosions and MRI bone marrow edema) were documented in each joint (n ‫؍‬ 12 joints). After surgery, sequential sections from throughout the whole joint were analyzed histologically for bone marrow changes, and these results were correlated with the MRI findings.Results. MRI bone erosion was recorded based on bone marrow inflammation adjacent to a site of cortical bone penetration. Inflammation was recorded based on either invading synovial tissue (pannus), formation of lymphocytic aggregates, or increased vascularity. Fatrich bone marrow was replaced by inflammatory tissue, increasing water content, which appears as bright signal enhancement on STIR MRI sequences. MRI bone marrow edema was recorded based on the finding of inflammatory infiltrates, which were less dense than those of MRI bone erosions and localized more centrally in the joint. These lesions were either isolated or found in contact with MRI bone erosions.Conclusion. MRI bone erosions and MRI bone marrow edema are due to the formation of inflammatory infiltrates in the bone marrow of patients with RA. This emphasizes the value of MRI in sensitively detecting inflammatory tissue in the bone marrow and demonstrates that the inflammatory process extends to the bone marrow cavity, which is an additional target structure for antiinflammatory therapy.

Rheumatoid arthritis (RA) leads to destruction of cartilage and bone. Whether rheumatoid arthritis also affects the adjacent bone marrow is less clear. In this study, we investigated subcortical bone marrow changes in joints from patients with RA. We describe penetration of the cortical barrier by synovial inflammatory tissue, invasion into the bone marrow cavity and formation of mononuclear cell aggregates with B cells as the predominant cell phenotype. B cells expressed common B cell markers, such as CD20, CD45RA, and CD79a, and were mature B cells, as indicated by CD27 expression. Plasma cells were also present and were enriched in the regions between aggregates and inflammatory tissue. Moreover, molecules for B cell chemoattraction, such as BCA-1 and CCL-21, homing, mucosal addressin cell adhesion molecule-1 and survival, BAFF, were expressed. Endosteal bone next to subcortical bone marrow aggregates showed an accumulation of osteoblasts and osteoid deposition. In summary, we show that synovial inflammatory tissue can reach the adjacent bone marrow by fully breaking the cortical barrier, which results in formation of B cell-rich aggregates as well as increased formation of new bone. This suggests that bone marrow is an additional compartment in the disease process of RA.

Objective To define the expression pattern of cadherin-11 in destructive pannus tissue of patients with rheumatoid arthritis and to determine if cadherin-11 expression in fibroblast-like synoviocytes controls their invasive capacity. Methods Cadherin-11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin-11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L-cell clones expressing wild-type cadherin-11, mutant cadherin-11, and empty vector transfected controls. The invasive capacity of L-cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin-11-Fc protein or control immunoglobulin was determined in Matrigel invasion assays. Results Immunohistochemistry revealed that cadherin-11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Invasion assays demonstrate a twofold increased invasive capacity of cadherin-11 transfected L-cells compared to L-cells transfected with E-cadherin or control vector. The invasive behavior of the L-cells stably transfected with a cadherin-11 construct that lacked the juxta-membrane cytoplasmic domain (cadherin-11 ΔJMD) was diminished to the level of vector control L-cells. Further, treatment with the cadherin-11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes. Conclusion These in vitro studies implicate a role for cadherin-11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis.

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In this exploratory open study, RTX exhibited significant efficacy in PsA patients with long-standing disease. Thus, RTX may have efficacy in PsA warranting a randomised controlled clinical trial.