Longitudinal differential gene expression and pathway analysis of Lyme disease. (A) Bar chart of the numbers of genes found to be upregulated or downregulated at Lyme disease diagnosis (V1), 3 weeks post-treatment (V2, after a standard course of antibiotics), and 6 months post-treatment (V5). (B) Venn diagram representing the number of DEGs between Lyme disease patients and controls at three time points. (C) Principal component analysis (PCA) of Lyme disease patients and controls at three time points on the basis of 1,759 unique DEGs identified at V1, V2, and V5. The asterisk represents a subject in the control group who looks like an outlier in the PCA plot but is not shown to be an outlier by PCA analysis of the control samples (see Fig. S2 in the supplemental material). Note that the PC3 axis in the PCA plot accounts for only 8% of the variance in the data set. (D to F) Top 10 disease and functional categories (D), top 10 canonical pathways (E), and top 10 upstream regulators (excluding drug categories) (F) predicted to be involved in Lyme disease at (V1, V2, and V5) with categories, pathways, and genes ranked by the negative log of the P value of the enrichment score. The color scheme is based on Z scores, with activation in orange, inhibition in blue, and undetermined directionality in gray. The red line represents the designated significance threshold (P < 0.05).
Researchers at UCSF and Johns Hopkins may have found a new way to diagnose Lyme disease, based on a distinctive gene “signature” in WBCs of patients infected with the tick-borne bacteria. Even though it is hard to diagnose, Lyme disease is still the most common vector-borne illness in the US, with 30,000 cases reported each year. With more accurate tests the number of people infected could turn out to be 10 times higher. The tick that transmits Lyme also harbors many other pathogens, and early diagnosis is critical in guiding appropriate treatment and preventing later complications of the illness.
Most people who contract the disease recover quickly with antibiotic treatment, but between 10 and 20% report persistent symptoms. Lyme disease has also been associated with arthritis, meningitis, facial palsy and in rare cases myocarditis leading to sudden death. To find better ways of diagnosing the disease, and discovering molecular pathways that might explain how Lyme disease could cause long-term symptoms, researchers used a next-generation sequencing technique, RNA-seq, to investigate the transcriptome – the genes that are being turned on – in peripheral blood mononuclear cells.
Researchers examined 29 patients before and after they received a 3-week course of antibiotic treatment and also 6 months later. Compared to patients with other active bacterial or viral infections, the Lyme disease patients had distinctive gene signatures that persisted for at least 3 weeks, even after they had taken the antibiotics. Some differences in the transcriptome lingered for 6 months.
6 months after Rx, 15 of the 29 patients in the study had fully recovered, while 13 had persistent symptoms, and one had dropped out. Despite the stark differences in how the patients reported feeling, the researchers could not detect transcriptional differences between the 2 groups. They said larger studies are needed to confirm this finding.
There were similarities between transcriptional changes after Lyme disease infection and other diseases. The acute phase of Lyme disease infection had similarities with influenza. At 6 months, gene signatures of Lyme disease patients showed some similarities to those from patients with immune diseases like SLE, RA and CFS (chronic fatigue syndrome). Measureable and persistent changes to the transcriptome may also be characteristic of a number of other infections, such as chronic hepatitis C. https://www.ucsf.edu/news/2016/02/401581/gene-signature-could-lead-new-way-diagnosing-lyme
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