Additional file 3 of Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

Additional file 3: Figure S3. ODE induces minimal evidence of arthritis with or without CIA. A) Arthritis inflammatory score increases in HLA-DR4 transgenic mice following 4 weeks of ODE exposure. B) In the setting of arthritis induction (CIA), ODE-induced arthritis inflammatory score increases in WT-CIA + ODE and DR4-CIA + ODE animals. Statistical difference versus saline-treated control mice is indicated by #p < 0.05

Additional file 1 of Xanthine oxidase inhibitor urate-lowering therapy titration to target decreases serum free fatty acids in gout and suppresses lipolysis by adipocytes

Additional file 1: Supplementary Figure 1. PLS-DA and RF analysis of serum metabolomic profiling at time zero. PLS-DA and RF analysis at time zero resulted in a good discrimination and prediction of the samples per BMI (A), but not per number of flares (B), or hyperuricemia (HU) > 8 mg/dL (C), or presence of tophi (D). Supplementary Figure 2. XOI-based ULT effects on serum metabolomic profiling. (A) PCA examining samples at time zero as well as at 12 and 24 weeks ULT titration to target. (B) Hierarchical clustering analysis at three time points. (C) Random Forest (RF) analysis using metabolite data derived from sera collected at baseline, or at 12 and 24 weeks ULT titration to target. (D) Top metabolites generated by RF analysis resulted in predictive accuracy of 52% (compared to 33% expected by random chance alone). Supplementary Figure 3. Validation of XOI-based ULT effects on xanthine and purine metabolism by serum metabolomic profiling. (A) Levels of ULT drugs included in the treatment and in metabolites related to purine and xanthine metabolism were significantly elevated in samples collected at 12- and 24-weeks treatment. Green: indicates significant difference (p≤0.05) between the groups shown, metabolite ratio of < 1.00. Light Green: narrowly missed statistical cutoff for significance 0.0

Table_2_Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis.XLSX

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.</p

Additional file 1 of Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

Additional file 1: Figure S1. Flow cytometry gating strategies depicted for lung cell identification of Ly6G+ neutrophils, CD3+CD4+ T cells, CD3+CD8+ T cells, CD19+CD11b− B2 B cells and CD19+CD11b+ B1 B cells

Additional file 4 of Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

Additional file 4: Figure S4. Co-localization of MAA, CIT, and vimentin in the setting of arthritis induction (CIA) with and without ODE. CIT- and MAA-modified proteins, CIT, and vimentin, and MAA and vimentin strongly co-localize in all treatment groups. Statistical difference (####p < 0.0001) versus saline

sj-docx-1-tab-10.1177_1759720X231201047 – Supplemental material for Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance

Supplemental material, sj-docx-1-tab-10.1177_1759720X231201047 for Rheumatoid arthritis disease activity and adverse events in patients receiving tofacitinib or tumor necrosis factor inhibitors: a post hoc analysis of ORAL Surveillance by George A. Karpouzas, Zoltán Szekanecz, Eva Baecklund, Ted R. Mikuls, Deepak L. Bhatt, Cunshan Wang, Gosford A. Sawyerr, Yan Chen, Sujatha Menon, Carol A. Connell, Steven R. Ytterberg and Mahta Mortezavi in Therapeutic Advances in Musculoskeletal Disease</p

Additional file 2 of Increased susceptibility to organic dust exposure-induced inflammatory lung disease with enhanced rheumatoid arthritis-associated autoantigen expression in HLA-DR4 transgenic mice

Additional file 2: Figure S2. Flow cytometry gating strategy for lung macrophage-monocyte subpopulations is depicted

Image_1_Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis.JPEG

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.</p

Plain language summary for the manuscript: Cardiovascular and cancer risk with tofacitinib in rheumatoid arthritis

This is a plain language summary (PLS) of an article published in a peer-reviewed scientific journal. This PLS is not peer-reviewed. The publisher of the original manuscript was not involved in the preparation of this PLS and has neither reviewed nor approved its content.</p

Image_2_Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis.JPEG

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.</p