第984回千葉医学会例会・第33回肺癌研究施設例会

<p>The baseline (pre) and the peak (post) values of anti-DNA Ab (Farr) (A), IgG-anti-dsDNA Ab (B), IgM-anti-dsDNA Ab (C), and IgG-anti-ssDNA Ab (D). The upper limit normal values are indicated by dashed lines. The post values are the highest titers observed during the follow-up periods. Each dot represents a single serum sample, and the data are presented as mean ± SEM. A paired <i>t</i>-test for intra-group comparison or the Mann-Whitney test for inter-group comparison was used. ns: not significant.</p

Serum cytokine levels before and 12 months after IFX treatment.

<p>The pre- and post-treatment levels of IL-6, IFN-γ, IFN-α2 and BAFF were compared between ADA-positive (+) and ADA-negative (-) groups. Data are presented as mean + SEM. A paired <i>t</i>-test for intra-group comparison and the Mann-Whitney test for inter-group comparison were used.</p

Additional file 1 of Role of DNA dioxygenase Ten-Eleven translocation 3 (TET3) in rheumatoid arthritis progression

Additional file 1: Supplementary Figure S1. Degeneration of TET3 mRNA induced by TNFα stimulation. Relative mRNA expression levels of TET3 in RA FLS (n = 3) treated with actinomycin D (Wako, 10 μg/mL), followed by stimulation with TNFα for 0, 0.5, 1, 2, and 6 hrs. Supplementary Figure S2. Relative mRNA expression levels of TET1/2/3 with or without TET3-knockdown. (A) RA FLS (n = 2) samples were used to study TET3 mRNA levels by qPCR. Data are mean ± SEM. (B) RA FLS (n = 3) samples were used to study TET3 protein levels by Western blotting. Supplementary Figure S3. Heat map of differentially expressed genes in all RA FLS with or without TNFα stimulation and TET3-knockdown. 2013 of all 21,448 genes were differentially expressed genes in 4 RA FLS groups (ANOVA F-test, P < 0.05) and analyzed. Red corresponds to gene upregulation and blue to gene downregulation. Supplementary Figure S4. Cell proliferation of FLS by TET3 expression. RA FLS (n=3) were transfected with control or TET3 siRNAs. Cell numbers of FLS were counted with Hemocytometer at day 1, 3, and 7. P value by the t-test

Additional file 3 of Role of DNA dioxygenase Ten-Eleven translocation 3 (TET3) in rheumatoid arthritis progression

Additional file 3

Additional file 2 of Role of DNA dioxygenase Ten-Eleven translocation 3 (TET3) in rheumatoid arthritis progression

Additional file 2: Supplementary Table S1. TET3-mediated upregulated genes. Supplementary Table S2. TET3-mediated downregulated genes. Supplementary Table S3. Results of functional enrichment analysis. Supplementary Table S4. KEGG pathway analysis. Supplementary Table S5. Demographic, clinical, and biochemical features of RA and OA patients whose synovial tissues were used in the experiments

Clinical features of the patients enrolled in this study.

<p>Clinical features of the patients enrolled in this study.</p

Neutrophils Are Essential As A Source Of Il-17 In The Effector Phase Of Arthritis

<div><p>Objective</p><p>Th17 has been shown to have a pivotal role in the development of arthritis. However, the role of IL-17 in the T cell-independent effector phase has not fully been examined. We investigated whether IL-17 is involved in the effector phase of arthritis by using K/BxN serum-induced arthritis model.</p><p>Methods</p><p>K/BxN serum was transferred into IL-17 knockout (KO) mice, SCID mice and their control mice, and arthritis was evaluated over time. In order to clarify the source of IL-17 in the effector phase, neutrophils or CD4+ T cells collected from IL-17 KO or control mice were injected into IL-17 KO recipient mice together with K/BxN serum. To examine if neutrophils secrete IL-17 upon stimulation, neutrophils were stimulated with immune complex in vitro and IL-17 in the supernatant was measured by ELISA.</p><p>Results</p><p>K/BxN serum-induced arthritis was much less severe in IL-17 KO mice than in WT mice. Since K/BxN serum-transferred SCID mice developed severe arthritis with high serum IL-17 concentration, we speculated neutrophils are the responsible player as an IL-17 source. When wild type (WT) but not IL-17 KO neutrophils were co-injected with K/BxN serum into IL-17 KO mice, arthritis was exacerbated, whereas co-injection of WT CD4+ T cells had no effect. In vitro, stimulation of neutrophils with immune complexcaused IL-17 secretion.</p><p>Conclusions</p><p>Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. The trigger of secreting IL-17 from neutrophils may be immune complex.</p></div

Anti-drug antibody (ADA) is associated with reduced clinical response.

<p>(A) Treatment efficacy defined as low disease activity (LDA) or remission at 6 months. Percentages and absolute numbers of each group of patients are indicated below the graphs. ADA positivity was based on the assessment of 6 months. Fisher’s exact test was used for comparison. (B) Cumulative drug retention rates. A log-rank test was used for comparison between the two groups.</p

Suppressor of TCR signaling-2 (STS-2) suppresses arthritis development in mice

<p><b>Objectives:</b> Suppressor of TCR signaling-2 (STS-2) is one of the RA susceptibility genes identified in genome-wide association studies (GWAS). We tried to verify the involvement of STS-2 on the development of autoimmune arthritis in a mouse model.</p> <p><b>Methods:</b> STS-2 knock-out (KO) and wild type (WT) mice were immunized with chicken type II collagen (CII). For CD4⁺ helper T cell (Th) subset analysis, intracellular cytokines in splenocytes and lymph node cells were stained and analyzed by flow cytometry. Regulatory T cell (Treg) function was analyzed by co-culturing effector CD4⁺T cells and Tregs collected from non-immunized mice.</p> <p><b>Results:</b> CII-immunized STS-2 KO mice developed arthritis more frequently than WT mice. Although the T cell activation profile and Th subset in spleen and LNs were similar between STS-2 KO and WT mice, STS-2 KO mice showed increased IL-2-producing CD4⁺T cells in spleen when compared with WT mice. Accordingly, STS-2 KO CD4⁺T cells promoted IL-2 production by TCR stimulation. However, STS-2 KO Tregs normally suppressed T cell proliferation.</p> <p><b>Conclusion:</b> We proved that STS-2 is involved in the arthritis development by collagen-induced arthritis. Higher IL-2 production from STS-2 KO T cells is suggested to have a main pathogenic role in arthritis development.</p

Inverse Association between Air Pressure and Rheumatoid Arthritis Synovitis

<div><p>Rheumatoid arthritis (RA) is a bone destructive autoimmune disease. Many patients with RA recognize fluctuations of their joint synovitis according to changes of air pressure, but the correlations between them have never been addressed in large-scale association studies. To address this point we recruited large-scale assessments of RA activity in a Japanese population, and performed an association analysis. Here, a total of 23,064 assessments of RA activity from 2,131 patients were obtained from the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Detailed correlations between air pressure and joint swelling or tenderness were analyzed separately for each of the 326 patients with more than 20 assessments to regulate intra-patient correlations. Association studies were also performed for seven consecutive days to identify the strongest correlations. Standardized multiple linear regression analysis was performed to evaluate independent influences from other meteorological factors. As a result, components of composite measures for RA disease activity revealed suggestive negative associations with air pressure. The 326 patients displayed significant negative mean correlations between air pressure and swellings or the sum of swellings and tenderness (p = 0.00068 and 0.00011, respectively). Among the seven consecutive days, the most significant mean negative correlations were observed for air pressure three days before evaluations of RA synovitis (p = 1.7×10⁻⁷, 0.00027, and 8.3×10⁻⁸, for swellings, tenderness and the sum of them, respectively). Standardized multiple linear regression analysis revealed these associations were independent from humidity and temperature. Our findings suggest that air pressure is inversely associated with synovitis in patients with RA.</p></div