- The Association of Disease Activity, Pro-Inflammatory Cytokines, and Neurotrophic Factors with Depression in Patients with Rheumatoid Arthritis. [Journal Article]
- BBBrain Behav Immun 2018 May 19
- Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are asso...
Inflammation and trophic factors (brain-derived neurotrophic factor [BDNF], vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and insulin-like growth factor-1) are associated with depression in the general population. Rheumatoid arthritis (RA) is a chronic representative inflammatory autoimmune disease; however, the association of disease activity, pro-inflammatory cytokines, and neurotrophic factors with depression has not been sufficiently investigated. Therefore, we determined the prevalence of depression and risk factors for depression and deterioration of depressive symptoms in RA patients. In addition, we analyzed the association between disease activity, pro-inflammatory cytokines, trophic factors, and depression in RA (N=474). Demographic and laboratory data were examined, and routine assessment of patient index data 3 (RAPID 3) and disease activity score 28-joint count C-reactive protein (DAS 28-CRP) was performed to assess disease activity of RA. Depression was measured using the Korean version of the Beck Depression Inventory-second edition (K-BDI II). A K-BDI score ≥18 was considered the cut-off for depression in accordance with a previous validation study. The serum level of pro-inflammatory cytokines and neurotrophic factors was assessed by enzyme-linked immune sorbent assay. The prevalence of depression was 32.4% in patients with RA. The severity of disease activity of RA (RAPID 3 score [OR 2.34; 95% confidence interval, CI 1.22-4.51], DAS 28-CRP [≥3.2] [OR 1.60, 95% CI 1.01-2.53]) and severity of fatigue (OR 1.26 95% CI 1.15-1.38) were associated with depression and deterioration of depressive symptoms in the multivariate analysis. Among the components of RAPID 3 and DAS 28-CRP, patient assessment for global health and abilities for daily performance were more related to depression. The level of pro-inflammatory cytokines (IL-1β, IL-6, TNF-alpha) was not related to depression. The level of BDNF was significantly lower in RA patients with depression and was negatively correlated with K-BDI II score. Depression was related with the level of fatigue, low expression of BDNF, and high RA disease activity, which was associated with impaired ability to perform activities of daily life. Strict control of fatigue and disease activity to improve one's capacity to perform daily life activities would be important to regulate depression. The level of BDNF might be one of the possible biomarkers to predict or monitor depression in patients with RA.
- Risk Factors for Intraarticular Heterotopic Bone Formation in the Temporomandibular Joint in Juvenile Idiopathic Arthritis. [Journal Article]
- JRJ Rheumatol 2018 May 15
- CONCLUSIONS: HBF within the TMJ is relatively common in patients with JIA receiving IAC injections for TMJ arthritis. Future prospective studies are required to delineate the risks posed by the injections themselves as opposed to the underlying disease activity, as well as to evaluate alternative forms of local therapy to the TMJ.
- TL1A mediates fibroblast-like synoviocytes migration and Indian Hedgehog signaling pathway via TNFR2 in patients with rheumatoid arthritis. [Journal Article]
- ECEur Cytokine Netw 2018 Mar 01; 29(1):27-35
- Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migr...
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by joints inflammation. One of the aggressive characteristics of RA fibroblast-like synoviocytes (FLS) is the tendency for migration in the local environment, which plays a central role in the RA pathogenesis. Tumor Necrosis Factor (TNF)-like cytokine 1A (TL1A) is a member of TNF superfamily, which has a role in autoimmunity and influences the RA-FLS behavior through TNF receptor 2 (TNFR2). We investigated the effect of TNF-like cytokine 1A (TL1A) on RA-FLS migration using patients' samples. Specifically, we examined the hedgehog signaling pathway which is a key regulator in chondrocyte growth and differentiation. We found that TL1A increased significantly the hedgehog homologue Indian hedgehog (IHH) and its receptor Patched 1, 2 (PTCH 1, 2) in RA-FLS. In addition, TL1A-stimulated RA-FLS promoted significantly IHH protein expression. However, both mRNA and protein levels decreased substantially after blocking TL1A with TNFR2 antagonist. The migratory property of RA-FLS was enhanced after stimulation of RA-FLS with TL1A, but was compromised following TL1A blockage. In conclusion, our study has revealed that TL1A modulated RA-FLS migration and Indian hedgehog signaling pathway using TNFR2.
- Anti-citrullinated protein antibody response after primary EBV infection in kidney transplant patients. [Journal Article]
- PlosPLoS One 2018; 13(5):e0197219
- Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, characterized by the presence of the highly disease-specific anti-citrullinated protein antibodies (ACPA) in approximat...
Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints, characterized by the presence of the highly disease-specific anti-citrullinated protein antibodies (ACPA) in approximately 70% of patients. Epstein-Barr virus (EBV) has previously been suggested to be involved in the pathophysiology of RA. However, given the high incidence of EBV in the general population and the difficulty of detecting initial infection, providing a direct link between EBV infection and RA development has remained elusive. We hypothesized that primary EBV infection may be a trigger for the development of the ACPA response in vivo. Using a unique cohort of 26 kidney transplant patients with a primary EBV infection, the presence of ACPA before and following infection was determined. No increase in IgG anti-CCP2 titers was detected following EBV infection. IgG anti-CCP2 antibodies were present in two patients and borderline positive in another. These three patients were HLA-DR4 negative. To test whether EBV infection may trigger a non-class switched anti-CCP2 response, IgM anti-CCP2 antibodies were analyzed. No general trend in the IgM anti-CCP2 response was observed following EBV infection. Since two out of the three IgG anti-CCP2 (borderline) positive patients were diagnosed with IgA nephropathy, 23 additional IgA nephropathy patients were tested for IgG anti-CCP2, regardless of their EBV status. All of these patients were IgG anti-CCP2 negative, indicating that IgG anti-CCP2 is not commonly present in IgA nephropathy patients. Collectively, these data do not support the hypothesis that EBV does trigger the highly RA specific ACPA response.
- [Diagnosis and treatment of rheumatoid arthritis:toward the best practice. The Pathophysiology in Rheumatoid Arthritis.] [Journal Article]
- CCClin Calcium 2018; 28(5):595-600
- Rheumatoid arthritis(RA)is one of the systemic autoimmune diseases characterized by progressive joint destruction with chronic synovitis. In the synovium, activated osteoclasts with plenty of inflamm...
Rheumatoid arthritis(RA)is one of the systemic autoimmune diseases characterized by progressive joint destruction with chronic synovitis. In the synovium, activated osteoclasts with plenty of inflammatory cytokines and metalloproteinases induce bone and cartilage destruction. Anti-cyclic citrullinated protein antibodies(ACPA)was recognized not only as a diagnostic marker but also as direct inducer of synovitis. In addition, environmental factors and background of daily life also contribute to the pathogenesis of RA, especially smoking and periodontitis are considered to be important factors for disease activities.
- Deleterious role of hepatitis B virus infection in therapeutic response among patients with rheumatoid arthritis in a clinical practice setting: a case-control study. [Journal Article]
- ARArthritis Res Ther 2018 May 02; 20(1):81
- CONCLUSIONS: HBV infection may play a deleterious role in radiographic and clinical outcomes in patients with RA, and HBV reactivation should be paid close attention during immunosuppressive therapy.
- One year in review 2018: pathogenesis of rheumatoid arthritis. [Review]
- CEClin Exp Rheumatol 2018 Mar-Apr; 36(2):175-184
- Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects joints. The several mechanisms involved in the development of the disease are not completely understood. ...
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that primarily affects joints. The several mechanisms involved in the development of the disease are not completely understood. It has been proposed that different environmental factors, such as cigarette smoking, occupational and atmospheric agents act as trigger stimuli for the development of RA in genetically predisposed individuals, leading to synovial hyperplasia and bone destruction. The initial disease stage of RA is associated with alteration of innate and adaptive immune system with consequent production of autoantibodies, targeting various molecules including modified self-epitopes. In the following stages of the disease, both the innate (e.g. dendritic cells, macrophages and neutrophils) and adaptive immune cells (e.g. B and T lymphocytes) contribute to the amplification and perpetuation of the chronic inflammatory state. The recognition of key cells, mediators and mechanisms implicated in the pathogenesis of RA could provide the basis for the development of new and precise disease-modifying anti-rheumatic drugs. Therefore, we reviewed the literature of the last year in order to find the new insights in RA pathogenesis.
- Chikungunya virus infection in Aruba: Diagnosis, clinical features and predictors of post-chikungunya chronic polyarthralgia. [Journal Article]
- PlosPLoS One 2018; 13(4):e0196630
- CONCLUSIONS: We identified 269 CHIKV patients after the first outbreak of Asian genotype CHIKV in Aruba in 2014-2015. RT-PCR yielded 59 (28%) additional CHIKV diagnoses compared to IgM antibody detection alone. Arthralgia, fever and skin rash were the dominant acute phase symptoms. pCHIK-CPA longer than 1 year affected 26% of cases and was predicted by female gender, high ACR-score and CHIKV-RNA detection beyond 7 days of symptom onset.
- Can a disaster affect rheumatoid arthritis status? A retrospective cohort study after the 2011 triple disaster in Fukushima, Japan. [Journal Article]
- IJInt J Rheum Dis 2018 Apr 26
- CONCLUSIONS: This is the first study to analyze detailed profiles of RA patients after a disaster. As methotrexate may prevent disease exacerbation, continuity of care for this common chronic disease should be considered in disaster settings.
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- Inflammatory biomarkers in saliva and serum of patients with rheumatoid arthritis with respect to periodontal status. [Journal Article]
- AMAnn Med 2018; 50(4):333-344
- CONCLUSIONS: Elevated serum concentrations of MMP-8 and IL-6 in CRA patients reflected chronic RA, while elevated salivary concentrations of MMP-8 levels in ERA patients reflected increased periodontal inflammation. Key messages Concentrations of inflammatory biomarkers in serum and saliva were different between patients with RA and healthy controls. Concentrations of MMP-8 and of IL-6 in serum were elevated in patients with chronic RA reflecting joint inflammation and the burden of established RA. Concentrations of MMP-8 in saliva was elevated already at the early stage of RA and the level of salivary MMP-8 was associated with poor periodontal health both in patients with early and in those with chronic RA.