Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis - Fig 1

A different clustering of metabolic ions was shown in the supervised orthogonal partial least squares-discriminant analysis (OPLS-DA) score plot (A1 and A2) from 32 patients with adult-onset Still’s disease (AOSD), 30 healthy subjects (control group), and quality control (QC). The comparisons in serum levels of the differentially expressed metabolites between AOSD patients and control group (B-N). For the box plots, the bottom and top of the boxes represent the 25th and 75th percentile, respectively. The top and bottom bars represent the entire stretch of the data points for the subjects, except the extreme points which are indicated with exact values of data. The hyphen within box indicates the median value. *p<0.05, **p<0.01, ***p<0.001, versus the control group.</p

Schematic representation depicts the metabolic imbalance in patients with adult-onset Still’s disease (AOSD).

(↑) represents up-regulated changes observed in AOSD; (↓) represents down-regulated changes observed in AOSD.</p

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis - Fig 3

A different clustering of metabolic ions in the OPLS-DA score plots from AOSD patients with different patterns of disease outcome (A). The comparisons in serum levels of the differentially expressed metabolites in AOSD patients with different patterns of disease outcome (B-N). *pFig 1 legend.</p

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis - Fig 2

A different clustering of metabolic ions was shown in the OPLS-DA score plot from 14 active AOSD patients, 18 inactive AOSD patients, and 30 healthy controls (A1). A different clustering of metabolic ions was shown in AOSD patients with different activity scores (A2). The correlation between serum levels of the altered metabolites and AOSD activity scores (B-N).</p

Metabolic Disturbances in Adult-Onset Still’s Disease Evaluated Using Liquid Chromatography/Mass Spectrometry-Based Metabolomic Analysis

<div><p>Objective</p><p>Liquid chromatography/mass spectrometry (LC/MS)-based comprehensive analysis of metabolic profiles with metabolomics approach has potential diagnostic and predictive implications. However, no metabolomics data have been reported in adult-onset Still’s disease (AOSD). This study investigated the metabolomic profiles in AOSD patients and examined their association with clinical characteristics and disease outcome.</p><p>Methods</p><p>Serum metabolite profiles were determined on 32 AOSD patients and 30 healthy controls (HC) using ultra-performance liquid chromatography (UPLC)/MS analysis, and the differentially expressed metabolites were quantified using multiple reactions monitoring (MRM)/MS analysis in 44 patients and 42 HC. Pure standards were utilized to confirm the presence of the differentially expressed metabolites.</p><p>Results</p><p>Eighteen differentially expressed metabolites were identified in AOSD patents using LC/MS-based analysis, of which 13 metabolites were validated by MRM/MS analysis. Among them, serum levels of lysoPC(18:2), urocanic acid and indole were significantly lower, and L-phenylalanine levels were significantly higher in AOSD patients compared with HC. Moreover, serum levels of lysoPC(18:2), PhePhe, uridine, taurine, L-threonine, and (R)-3-Hydroxy-hexadecanoic acid were significantly correlated with disease activity scores (all p<0.05) in AOSD patients. A different clustering of metabolites was associated with a different disease outcome, with significantly lower levels of isovalerylsarcosine observed in patients with chronic articular pattern (median, 77.0AU/ml) compared with monocyclic (341.5AU/ml, p<0.01) or polycyclic systemic pattern (168.0AU/ml, p<0.05).</p><p>Conclusion</p><p>Thirteen differentially expressed metabolites identified and validated in AOSD patients were shown to be involved in five metabolic pathways. Significant associations of metabolic profiles with disease activity and outcome of AOSD suggest their involvement in AOSD pathogenesis.</p></div

Retention time and LC/MRM-MS parameters for 13 standard compounds and 2 internal standard.

<p>Retention time and LC/MRM-MS parameters for 13 standard compounds and 2 internal standard.</p

Additional file 1: of Association between autophagy and inflammation in patients with rheumatoid arthritis receiving biologic therapy

Figure S1. Representative cytometric histograms of Cyto-ID staining in circulating CD4+ T cells (A1), CD8+ T cells (A2), and CD19+ B cells (A3) from one patient with rheumatoid arthritis (RA) and one healthy control subject (HC). Comparisons of autophagosome levels reflected by Cyto-ID-staining MFI, in CD4+ T cells (B), CD8+ T cells (C) and CD19+ B cells (D) between patients with RA and HC. Data are presented as box plot diagrams, with the box encompassing the 25th percentile (lower bar) to the 75th percentile (upper bar). The horizontal line within the box indicates median value for each group. *p < 0.05 versus HC. Representative cytometric histograms of Cyto-ID staining in peripheral blood (PB)-derived granulocytes (E) and synovial fluid (SF)-derived granulocytes (F). Comparisons of autophagosome levels in PB-derived and SF-derived granulocytes in patients with RA (G). (TIF 1427 kb

Eighteen differentially expressed metabolites identified in AOSD relative to healthy control in the first stage of metabolomics analysis.

<p>Eighteen differentially expressed metabolites identified in AOSD relative to healthy control in the first stage of metabolomics analysis.</p

Elevated Neopterin Levels Are Associated with Increased Tuberculosis Risk in Rheumatoid Arthritis Patients with QuantiFERON Conversion during Biologic Therapy - Fig 4

<p>Comparison of plasma levels of non-stimulated (A) and stimulated (B) neopterin and IFN-γ levels in QFT-G assay for 54 RA QFT-G converters with and without developing active TB. Seven QFT-G converters who developed active TB are marked (X). Strong responses equal to or greater than <u>2.74 IU/ml</u> for the QFT-G assay are determined by receiver-operating characteristic (ROC) curves analysis. The dotted line represents the cutoff value of 7.36pg/ml for non-stimulated neopterin levels and 5045pg/ml for stimulated neopterin levels. (C) The changes in TB-antigen-stimulated neopterin levels in seven QFT-G converters who developed TB during the period of biologic therapy and after the completion of anti-TB therapy. <i>P</i>-value was determined by Wilcoxon signed rank test.</p

Flow chart shows the distribution of results of QuantiFERON-TB Gold In-Tube (QFT-GIT) assay in 238 patients with rheumatoid arthritis (RA) before and after anti-TNF-α therapy.

<p>Seven patients developed active tuberculosis (TB) disease after anti-TNF-α therapy. LTBI: latent TB infection; INHP: isoniazid prophylaxis; QFT-GIT (+): positive QFT-GIT result; QFT-GIT (-): negative QFT-GIT result. QFT-GIT conversions were defined as: 1) baseline IFN-γ <0.35 IU/ml and follow-up IFN-γ≧0.35 IU/ml; and 2) baseline IFN-γ <0.35 IU/ml and follow-up IFN-γ≧0.70 IU/ml.</p