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Title: Host derived markers of lyme disease and other spirochaetal infections : their discovery and diagnostic potential
Author: Joyner, Greg
ISNI:       0000 0004 9358 4163
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2020
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UK laboratory diagnosis of Lyme disease involves the Standard Two-Tier serological approach. The negative predictive value of the test has been challenged, particularly in the early stages of disease. In order to better understand the host response to Lyme disease and to identify any potential host biomarkers that may correlate with early infection, proteomic and transcriptomic analyses were undertaken on Lyme disease patient samples. Label free quantitative spectrometry was used to measure and compare the serum proteome of seropositive patients against that of individuals that had tested seronegative for Lyme disease and a control group consisting of samples from normal healthy donors and patients with related infectious disease including leptospirosis and syphilis. Seropositive and seronegative individuals were found to be remarkably similar at the serum proteome level. Of the 12 proteins found to be at significantly different abundance between groups, the protein Lipocalin-2 was of particular interest due to role its role modulation of immune responses. Further analysis by ELISA in additional samples showed that Lipocalin-2 was significantly increased in Lyme disease positive patients when compared to normal healthy donors. Whole blood samples from patients with Lyme disease were then RNA sequenced and differential gene analysis was performed using sequencing data for healthy controls. Several pathways associated with bacterial immune response in the host were identified, together with actin rearrangement and oxidative stress pathways. eIF2 signalling was found to be significantly reduced in patients with early Lyme disease. The pathway has previously been identified as being down regulated during Lyme disease. In later samples from patients, following antibiotic therapy, eIF2 signalling levels were found to increase back towards those seen in control samples from normal/healthy individuals.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral