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

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

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

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

Multiplex predictors of imminent RA diagnosis.

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

The number of elevated autoantibodies and cytokines increase as individuals in the preclinical period approach the clinical diagnosis of RA.

<p>A–C, Mean titers of CCP2 (A), mean total number of ACPAs (B), and mean total number of cytokines (C) were evaluated at each time preclinical timepoint demonstrating a parallel rise in number of ACPA epitopes with rise in anti-CCP2 titer. D, The percent of subjects with elevated levels of each cytokine was evaluated in relation to number of ACPA subtypes present (representative examples of 48 measured cytokines) E, The proportion of subjects positive for each ACPA subtype was evaluated over the preclinical period. The X axis represents days relative to the diagnosis of RA. The Y axis represents the proportion of pre-clinical RA patients with positive value for each marker relative to total number of specimens available for analysis at that timepoint. A–E, Anti-CCP2 antibody titers were measured by CCP2 ELISA (A), ACPA subtypes were measured using a custom multiplex autoantigen bead array, serum cytokine concentrations were measured using commercial bead based multiplex cytokine kits.</p

Subject demographics.

<p>Subject demographics.</p

Accumulation of ACPA fine specificity before and concurrent with anti-CCP2 antibody seroconversion.

<p>A, Paired SAM analysis was performed on serum specimens from pre-clinical RA patients from whom at least 2 specimens were available prior to anti-CCP2 antibody seroconversion. B, Paired SAM analysis was performed on serum specimens from pre-clinical RA patients for whom a serum specimen was available both prior to and after anti-CCP2 antibody seroconversion. The heatmap represents absolute change in Z-score* from the first to the second timepoint. *Z-score represents the number of standard deviations above or the below the mean level observed in control subjects for each cytokine or autoantibody thus increase in Z-score represents increased change from normal population.</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