Serum Amyloid A levels are associated with elevated liver function tests.

<p>Lyme patients were separated into two populations based on normal (n = 24) vs. elevated liver enzyme tests (n = 20) and the levels of Serum Amyloid A (Panel A) and CRP (Panel B) were compared at multiple time points relative to healthy controls (n = 23). Serum amyloid A (p = 0.036) and CRP (p = 0.017) levels are significantly different between Lyme patients with high liver function tests at the pre-treatment visit. Both groups are significantly different from controls at (p<0.0005), but are not different from each other or controls, at both the Post-treatment and 6 Month follow-up visits. There is no significant difference in CRP levels between high and normal liver function groups, however both are significantly different from controls (p<0.0005).</p

Correlation Analysis of Key Mediators.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093243#pone-0093243-t003" target="_blank">Table 3</a> shows the relationship between acute, pre-treatment levels of key immune mediators of early Lyme disease as discussed in this paper. Pearson correlations were used for all analyses. A significant correlation can be seen between CXCL10, CXCL9 and CCL19. CRP shows a significant positive correlation with Serum Amyloid A (SAA). IL-6 does not correlate with either CRP or SAA.</p

Acute Lyme Disease patient subsets defined by circulating mediators versus clinical phenotypes.

<p><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093243#pone-0093243-t002" target="_blank">Table 2</a> shows group differences based on the heat map generated using SAM (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0093243#pone-0093243-g001" target="_blank">Figure 1</a>). No demographic differences between groups were seen. Categorical variables were compared using Fisher's Exact tests, while continuous variables were compared using unpaired t-tests. Lymphocyte values given are mean (standard deviation), while other values given are a percentage of the respective subset. Number of symptoms pre-treatment is defined as the number of symptoms reported by the patient during structured interview by the principle investigator (JNA) or study staff (LAC). Illness duration is defined as the period of time between first sign or symptom of disease and presentation for treatment and enrollment in the study.</p>a<p>Acute Lyme Mediator High n = 26; Acute Lyme Mediator Low n = 17;</p>b<p>Acute Lyme Mediator High n = 27; Acute Lyme Mediator Low n = 15.</p

Serostatus versus T Cell Chemokine Levels.

<p>Cutoffs in early Lyme disease cases were created for CXCL10, CXCL9, and CCL19 based on being higher or lower than controls. The columns show differences between those who are sero-positive at either time of diagnosis or immediately following treatment and those who are negative at both time points for these three biomarkers. CXCL10 and CXCL9 show differences in the association between those who are sero-positive and sero-negative (p = 0.003 and p = 0.004, respectively). There is no statistical difference in the association between serogroups for CCL19.</p

Chemokine levels in Lyme disease before and after treatment.

<p>Displayed are the levels of the chemokines CXCL10 (Panel A), CCL19 (Panel B), CXCL9 (Panel C) and CXCL8 (Panel D) measured in the serum of Lyme patients (n = 44) pre-treatment (acute disease) and post-treatment (4 weeks following diagnosis) as compared to healthy controls (n = 23). Horizontal bars represent the medians for each sample group.</p

Elevated Immune Mediators in Lyme Disease.

<p>Serum samples from patients with diagnosed acute Lyme disease (n = 44, red) and healthy controls (n = 23, black) were assayed for the presence of 58 soluble mediators and 7 acute phase proteins using an optimized multiplex-based assay system. Displayed are those mediators that show significant changes (q<0.1%) in Lyme patients vs. controls. (Panel A) Results are displayed as a heat map to visualize differences in mediator levels in Acute Lyme patients relative to controls. (Panel B) Unsupervised hierarchical clustering of the results was performed, and the output displayed as a heatmap. This analysis resulted in the formation of two clusters, including a “mediator high” cluster that contains samples derived from patients with acute <i>B. burgdorferi</i> infection who exhibited elevated serum inflammatory mediators. The second “mediator low” cluster includes a subset of samples from acute <i>B. burgdorferi</i> infection as well as the matched healthy controls, both of which exhibited low levels of inflammatory mediators.</p

Anti-Insulin Immune Responses Are Detectable in Dogs with Spontaneous Diabetes

<div><p>Diabetes mellitus occurs spontaneously in dogs. Although canine diabetes shares many features with human type-1 diabetes, there are differences that have cast doubt on the immunologic origin of the canine disease. In this study, we examined whether peripheral immune responses directed against islet antigens were present in dogs with diabetes. Routine diagnostics were used to confirm diabetic status, and serum samples from dogs with (N = 15) and without (N = 15) diabetes were analyzed for the presence of antibodies against islet antigens (insulin, glutamic acid decarboxylase, insulinoma-associated protein tyrosine phosphatase, and islet beta-cell zinc cation efflux transporter) using standard radioassays. Interferon-γ production from peripheral blood T cells stimulated by porcine insulin and by human insulin was tested using Elispot assays. Anti-insulin antibodies were detectable in a subset of diabetic dogs receiving insulin therapy. Pre-activated T cells and incipient insulin-reactive T cells in response to porcine or human insulin were identified in non-diabetic dogs and in dogs with diabetes. The data show that humoral and cellular anti-insulin immune responses are detectable in dogs with diabetes. This in turn provides support for the potential to ethically use dogs with diabetes to study the therapeutic potential of antigen-specific tolerance.</p></div

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

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