High sensitivity method for early Lyme disease detection
Inventors
Belisle, John T. • Molins, Claudia R. • Wormser, Gary P.
Assignees
New York Medical College • US Department of Health and Human Services • Colorado State University Research Foundation
Publication Number
US-10669567-B2
Publication Date
2020-06-02
Expiration Date
2036-02-17
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Abstract
The present disclosure provides methods for detecting early Lyme disease. The present disclosure provides a biosignature indicative of the presence or absence of Borrelia burgdorferi infection.
Core Innovation
The invention provides methods for detecting early Lyme disease through the identification of a biosignature indicative of the presence or absence of infection by Borrelia species, particularly Borrelia burgdorferi. The core technique involves analyzing a test biological sample from a subject using high resolution mass spectrometry (MS), specifically liquid chromatography-mass spectrometry (LC-MS), to obtain abundance values for at least forty-four molecular features. These abundance values form a biosignature that can be compared to control samples to diagnose infection.
Early Lyme disease presents diagnostic challenges because current antibody-based diagnostics are highly sensitive and specific only for late manifestations of the disease but have low sensitivity (29%-40%) in early stages. Direct detection methods like culture or nucleic acid amplification also have low sensitivity (≤50%) early on. The diagnosis often relies on clinical recognition of erythema migrans skin lesions, which can be confused with other skin conditions, leading to potential misdiagnosis. Therefore, the invention solves the problem of insufficient sensitivity and specificity in early Lyme disease detection by providing a novel diagnostic method based on metabolomic biosignatures obtained by high resolution MS.
Claims Coverage
The patent claims four main inventive features centered on a method for diagnosing and treating early Lyme disease using molecular feature biosignatures, the use of high resolution mass spectrometry technology, and the profiling of molecular feature abundance values.
Method for diagnosing and treating early Lyme disease using molecular feature biosignature
A method to diagnose early Lyme disease in a subject by obtaining a set of abundance values for at least forty-four molecular features from a test biological sample via high resolution mass spectrometry, and administering antibiotic treatment upon indication of Lyme disease.
Expansion of molecular feature set for improved detection
The ability to include an abundance value for any one or more of molecular features MF #45-95 from a defined molecular feature table to refine the biosignature and diagnostic accuracy.
Use of liquid chromatography-mass spectrometry (LC-MS) for molecular feature analysis
Employment of a high resolution mass spectrometry system comprising LC-MS to obtain abundance values for molecular features, specifically measuring the area under the peak of the monoisotopic mass of each molecular feature.
Diagnostic method with defined specificity and sensitivity distinguishing early Lyme disease
The method correctly distinguishes subjects with early Lyme disease from controls with a specificity of at least 90%, identifies at least 77% of serology negative early Lyme disease subjects, and compares test biological sample molecular feature abundance values relative to controls including healthy subjects and subjects with diseases having overlapping symptoms or serologic cross-reactivity.
In summary, the claims cover a method of diagnosing and treating early Lyme disease by comparing molecular feature abundance profiles obtained by LC-MS against controls, encompassing a defined set of molecular features, and enabling improved sensitivity and specificity over existing serological methods.
Stated Advantages
Improved sensitivity (84%-95%) and specificity (90%-100%) for early Lyme disease detection compared to current two-tier serologic testing, particularly in early infection stages where antibody response is not robust.
Ability to detect early Lyme disease prior to detectable antibody responses, overcoming a major limitation of conventional diagnostics.
Provides a novel nonantibody test that reduces misdiagnosis confusion with diseases having overlapping symptoms or serologic cross-reactivity.
Potential for earlier and more accurate patient management and treatment initiation, reducing progression of symptoms and improving clinical outcomes.
Documented Applications
Diagnosis of early Lyme disease in human subjects.
Differentiation of early Lyme disease patients from healthy controls, patients with overlapping symptoms such as syphilis and fibromyalgia, and patients exhibiting serologic cross-reactivity or other spirochetal infections.
Monitoring Lyme disease progression and response to therapy through analysis of biological samples collected over time.
Use in clinical laboratory settings employing LC-MS technology for metabolic profiling.
Guidance for administering appropriate antibiotic treatment based on molecular feature biosignature detection of infection.
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