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Metabolic Response in Patients with Post-Treatment Lyme Disease Symptoms/Syndrome

ABSTRACT: Post-treatment Lyme Disease Symptoms/Syndrome (PTLDS) occurs in approximately 10% of Lyme disease patients following antibiotic treatment. Objective biomarkers or specific clinical symptoms to identify PTLDS patients do not currently exist and the PTLDS classification is based on the report of persistent subjective symptoms for ≥ 6 months following antibiotic treatment for Lyme disease. Untargeted liquid chromatography-mass spectrometry metabolomics was used to define metabolic changes that occurred longitudinally in PTLDS and clinically cured non-PTLDS Lyme patients from two separate cohorts. An elastic net regularization model was applied to define the metabolites that classified PTLDS and non-PTLDS patients at different time points, and the PTLDS defining metabolites were evaluated in two sample cohorts using linear discriminant analysis. This study determined that observable metabolic alterations occur between PTLDS and non-PTLDS patients at multiple time points. These metabolic alterations discriminated between PTLDS and non-PTLDS patients and consisted of metabolites of glycerophospholipid, bile acid and acylcarnitine metabolism. Longitudinal analyses showed distinct patterns in metabolite abundance changes that indicated a greater variability in PTLDS vs non-PTLDS patients. These data provide evidence that an objective metabolite-based measurement can distinguish patients with PTLDS and help understand the underlying biochemistry of PTLDS.

ORGANISM(S): Human Homo Sapiens

TISSUE(S): Blood

DISEASE(S): Lyme Disease

SUBMITTER: John Belisle

PROVIDER: ST001391 | MetabolomicsWorkbench | Thu May 28 00:00:00 BST 2020

REPOSITORIES: MetabolomicsWorkbench

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Project description:In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, virus genetic variants are still circulating among vaccinated individuals with different symptomatology disease cases. Understanding the protective or disease associated mechanisms in vaccinated individuals is relevant to advance in vaccine development and implementation. To address this objective, serum protein profiles were characterized by quantitative proteomics and data analysis algorithms in four cohorts of vaccinated individuals uninfected and SARS-CoV-2 infected with asymptomatic, nonsevere and severe disease symptomatology. The results showed that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective or disease associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In nonsevere cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins including the Spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

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Metabolic Response in Patients with Post-Treatment Lyme Disease Symptoms/Syndrome

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