Figure 1.
Elevated Immune Mediators in Lyme Disease.
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 B. burgdorferi infection who exhibited elevated serum inflammatory mediators. The second “mediator low” cluster includes a subset of samples from acute B. burgdorferi infection as well as the matched healthy controls, both of which exhibited low levels of inflammatory mediators.
Table 1.
Cohort Characteristics.
Table 2.
Acute Lyme Disease patient subsets defined by circulating mediators versus clinical phenotypes.
Figure 2.
Chemokine levels in Lyme disease before and after treatment.
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.
Table 3.
Correlation Analysis of Key Mediators.
Figure 3.
Elevated Inflammatory Mediators in Lyme Disease.
Serum levels of CRP (panel A), Serum Amyloid A (Panel B) and IL-6 (Panel C) were measured in healthy controls (n = 23) and at various times during the course of diagnosis and treatment in Lyme patients (n = 44). CRP, Serum Amyloid A and IL-6 levels are significantly elevated at diagnosis (pre-treatment). CRP and Serum Amyloid A levels return to control levels after treatment while IL-6 levels persist.
Figure 4.
Chemokine levels are associated with elevated liver function tests.
Lyme patients were separated into two populations based on normal (n = 24) vs. elevated liver enzyme tests (n = 20) and the levels of CXCL10 (Panel A), CXCL9 (Panel B) and CXCL10 (Panel C) compared at three visits (pre-treatment, post-treatment, and 6 months) relative to healthy controls (n = 23). All three chemokines are significantly different between Lyme patients with high liver function tests and those with normal liver function tests at the pre-treatment visit. This difference was not observed at later time points.
Figure 5.
Serum Amyloid A levels are associated with elevated liver function tests.
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).
Table 4.
Serostatus versus T Cell Chemokine Levels.
Figure 6.
CXCR3 Expressing CD4+ T cell levels correlate with serum CXCL10.
Panel A: CXCR3 expressing CD4+ T cells were detected using polychromatic flow cytometry. Displayed is a representative plot. Panel B: The frequency of CXCR3+CD4+ T cells among total CD4+ PBMCs were determined in Lyme patients prior to treatment (cases, n = 44) and healthy controls (n = 23). Levels of CXCR3+CD4+ T cells were lower in cases vs. controls at pre-treatment (p = 0.0105). Panel C. The levels of blood CXCR3+CD4+ T cells were negatively correlated CXCL10 serum levels in pretreatment early Lyme disease cases (p = 0.0375).