Osteopontin is critically involved in rheumatoid arthritis; however, the molecular cross-talk between osteopontin and joint cell components that leads to the inflammatory joint destruction is largely unknown. We found that not only osteopontin but also tenascin-C and their common receptor, α9 integrin, are expressed at arthritic joints. The local production of osteopontin and tenascin-C is mainly due to synovial fibroblasts and, to a lesser extent, synovial macrophages. Synovial fibroblasts and macrophages express α9 integrin, and autocrine and paracrine interactions of α9 integrin on synovial fibroblasts and macrophages and its ligands contribute differently to the production of proinflammatory cytokines and chemokines. α9 integrin is also involved in the recruitment and accumulation of inflammatory cells. Inhibition of α9 integrin function with an anti-α9 integrin Ab significantly reduces the production of arthrogenic cytokines and chemokines and ameliorates ongoing arthritis. Thus, we identified α9 integrin as a critical intrinsic regulator that controls the development of autoimmune arthritis.
Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA.
The authors reported 8 infected TEAs: 5 cases were revised, 2 with the brace, 1 had above the elbow amputated. The regular and meticulous follow up and application of the elbow protector were useful to prevent infection of post-TEAs using Kudo's prosthesis in RA. Since 2008, there have been no infection of post TEAs and revised TEAs.
BackgroundAnti-cyclic citrullinated peptide antibodies (Anti-CCP Ab) are well-established serological markers that show high sensitivity and specificity in diagnosing early rheumatoid arthritis (RA). Furthermore, Anti-CCP Ab is reported to be associated with bone erosions of RA. Therefore, Anti-CCP Ab positive RA patient can be a candidate for intensive treatment.ObjectivesUpper measurement limit of Anti-CCP Ab increased recently up to 1200 units. High level of Anti-CCP Ab may be a predictor of the profound therapy for RA. To understand the importance of Anti-CCP Ab level, we evaluated RA patients with high titer Anti-CCP Ab in relationship to the other activity markers of RA and the intensity of the treatment for RA.MethodsTotal of 186 RA patients with Anti-CCP Ab higher than 30 units was included in this study. Baseline markers such as CRP, MMP-3, RF and anti-CCP Ab were measured at the entry of the study. Relationship among these markers ware evaluated and examined using statistical significance for the single-factor ANOVA and the multiple comparisons. Among those cases 131 cases were treated conservatively with biologics and/or DMARDs and were followed up more than one year. We graded them from I to IV by the intensity of the treatment. Grade I: Biological agent. Grade II: Methotrexate (MTX) more than 12mg or combination with more than 3 DMARDS Grade III: MTX 6–11mg or combination with two recommended DMARDS Grade IV: single use of DMARDS including MTX less than 5mg.ResultsThere was no relationship between titers of Anti-CCP Ab and titers of RF. We found significant statistical correlation between anti-CCP antibody titers and inflammatory markers such as CRP and MMP-3. There was significant statistical correlation between CRP and MMP-3.In terms of treatment intensity, strong intensity group showed high titer of anti-CCP Ab and CRP. Titer of RF and MMP-3 level did not have any relationship with the treatment intensity. In cases treated with biologics, anti-CCP Ab and CRP were significantly higher compared to non-biologic case group. In 80% of cases treated with biologics titer of anti-CCP was more than 200 units. However, non-biologic treatment was continued in more than 50% of cases with anti-CCP Ab higher than 200 units.ConclusionsEven though we treated cases based on the severity of the symptoms of the patient and response in laboratory data, high anti-CCP Ab titers and CRP at the base line were most associated with the treatment intensity after 1 year. The results of our study suggest that the titer of anti-CCP Ab can be better a predictor of the treatment intensity than MMP-3 and RF.Disclosure of InterestNone declared
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