Cover and contents : “Proceedings of the 11th CEReS Symposium on Enviromental Remote Sensing” February 23, 2009

2009年2月23日（月） 於 千葉大学けやき会

Chemical Proteomic Platform To Identify Citrullinated Proteins

Anti-citrullinated protein antibodies (ACPAs) are a hallmark of rheumatoid arthritis (RA) and are routinely used for disease diagnosis. Protein citrullination is also increased in cancer and other autoimmune disorders, suggesting that citrullinated proteins may serve as biomarkers for diseases beyond RA. To identify these citrullinated proteins, we developed biotin-conjugated phenylglyoxal (biotin-PG). Using this probe and our platform technology, we identified >50 intracellular citrullinated proteins. More than 20 of these are involved in RNA splicing, suggesting, for the first time, that citrullination modulates RNA biology. Overall, this chemical proteomic platform will play a key role in furthering our understanding of protein citrullination in rheumatoid arthritis and potentially a wider spectrum of inflammatory diseases

Median (25th, 75th Percentile)^* levels of adiponectin and inflammatory markers by high-risk autoantibody profile (HRP) phenotype in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.

<p>Median (25th, 75th Percentile)^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0199578#t002fn001" target="_blank">*</a>} levels of adiponectin and inflammatory markers by high-risk autoantibody profile (HRP) phenotype in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.</p

Modification of the association between adiponectin and inflammatory markers (A through H) by HRP status using linear mixed models in the studies of the Etiology of rheumatoid arthritis.

<p>This figure presents the interaction between adiponectin and High-Risk profile autoantibody (HRP) status in 257 serum and plasma samples from clinic visits of 144 first degree-relatives of RA patients in the Studies of the Etiology of Rheumatoid Arthritis. All analyses were adjusted for age, sex, ethnicity, BMI, pack-years of smoking, and current use of cholesterol-lowering medications.</p

Population characteristics by high-risk autoantibody profile (HRP) phenotype in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.

<p>Population characteristics by high-risk autoantibody profile (HRP) phenotype in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.</p

Association between adiponectin and markers of inflammation in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.

<p>Association between adiponectin and markers of inflammation in 257 serum/plasma samples from clinic visits of 144 FDRs from the studies of the Etiology of rheumatoid arthritis (SERA) cohort.</p

Intraperitoneal treatment with imatinib suppresses IL-1-independent MSU crystal-induced acute arthritis.

<p>(<b>A</b>) Changes in ankle thickness after i.a injection of 2.0 mg MSU or PBS in <i>IL-1R1</i>^<i>-/-</i> mice (<i>n</i> = 8-9/group) pre-treated with imatinib (100 mg/kg) or PBS twice a day starting 24 h before the injection of MSU crystals. Data are shown as means ± SEM of data pooled from the two independent experiments performed. *** = <i>P</i> < 0.001 <i>vs</i>. indicated group by repeated measures two-way ANOVA. (<b>B</b>) H&E-stained sections of ankle showing MSU injection sites 24 h after injection of 2 mg MSU crystals in <i>IL-1R1</i>^<i>-/-</i> pre-treated with imatinib (100 mg/kg) or PBS. Original magnification: x20.</p

Subject demographics.

<p>Subject demographics.</p

Multiplex predictors of imminent RA diagnosis.

<p>Multiplex predictors of imminent RA diagnosis.</p

Prediction of imminent RA using multiplex biomarkers.

<p>Multiple logistic regression was performed to identify markers from the reduced set of 21 antibodies and 38 cytokines which could classify pre-clinical RA subjects as being within 2 years of the onset of clinical RA. 5-fold cross validation was performed and common markers selected for final validation. A, Demonstrated is a receiver operating characteristic (ROC) curve using the panel of markers listed in table 3. B–C, Mean and standard deviation of values for each individual autoantibody (B) or cytokine (C) contributing to prediction of imminent onset RA as measured among controls, those RA patients at a timepoint greater than 2 years prior to RA onset, or those within 2 years of clinical RA onset.</p