Serum Epitope Repertoire Analysis Enables Early Detection of Lyme Disease with Improved Sensitivity in an Expandable Multiplex Format Immunoassays
Widely employed diagnostic antibody serology for Lyme disease, known as standard two-tier testing (STTT), exhibits insufficient sensitivity in early Lyme disease, yielding many thousands of false-negative test results each year. Given this problem, we applied serum antibody repertoire analysis (SERA), or next-generation sequencing (NGS)-based serology, to discover IgG and IgM antibody epitope motifs capable of detecting Lyme disease-specific antibodies with high sensitivity and specificity. Iterative motif discovery and bioinformatic analysis of epitope repertoires from subjects with Lyme disease (n = 264) and controls (n = 391) yielded a set of 28 epitope motifs representing 20 distinct IgG antibody epitopes and a set of 38 epitope motifs representing 21 distinct IgM epitopes, which performed equivalently in a large validation cohort of STTT-positive samples. In a second validation set from subjects with clinically defined early Lyme disease (n = 119) and controls (n = 257), the SERA Lyme IgG and IgM assay exhibited significantly improved sensitivity relative to STTT (77% versus 62%; Z-test; P = 0.013) and improved specificity (99% versus 97%). Early Lyme disease subjects exhibited significantly fewer reactive epitopes (Mann-Whitney U test; P
Conditions: Lyme Disease; Lyme Neuroborreliosis; Lyme Arthritis; Unknown Origin Fever Intervention: Device: Scientific Consciousness Interface Operations (SCIO) Class II FDA approved medical device Sponsor: Kasey Phifer Recruiting
Borreliosis (Lyme disease) is a spirochetal disease caused by the species complex ofBorrelia burgdorferi transmitted byIxodes spp. ticks. Recorded to be the most common tick ‐borne disease in the world, the last two decades have seen an increase in disease incidence and distribution, exceeding 360 000 cases in Europe alone. If untreated, infection may cause skin symptoms, arthritis, and neurological or cardiac complications. Borrelia spirochetes have developed strate gies to evade the mammalian host immune system. These include the complement system, which is an important first‐line defense mechanism against...
In conclusion, These results reveal new possibilities for the treatment of Lyme arthritis. PMID: 32829087 [PubMed - as supplied by publisher]
AbstractBorreliosis (Lyme disease) is a spirochetal disease caused by the species complex ofBorrelia burgdorferi transmitted byIxodes spp. ticks. Recorded to be the most common tick ‐borne disease in the world, the last two decades have seen an increase in disease incidence and distribution, exceeding 360 000 cases in Europe alone. If untreated, infection may cause skin symptoms, arthritis, neurological or cardiac complications. Borrelia spirochetes have developed strategies to evade the mammalian host immune system. These include the complement system, which is an important first‐line defence mechanism against invadin...
Pathogen specific antibody responses need to be tightly regulated to generate protective but limit self-reactive immune responses. While loss of humoral tolerance has been associated with microbial infections, the pathways involved in balancing protective versus autoreactive antibody responses in humans are incompletely understood. Studies in classical mouse model systems have provided evidence that balancing of immune responses through inhibitory receptors is an important quality control checkpoint. Genetic differences between inbred mouse models and the outbred human population and allelic receptor variants not present i...
Title: What Happens if You Go Untreated for Lyme Disease?Category: Diseases and ConditionsCreated: 6/17/2020 12:00:00 AMLast Editorial Review: 6/29/2020 12:00:00 AM
Lyme borreliosis is the most prevalent tick-borne disease in the northern hemisphere.1 Over the last decades, marked increases in the incidence of Lyme borreliosis have been reported in several Western European countries and the United States (US), with substantial impact on public health.2 –6 Erythema migrans is the most common early skin manifestation of the disease, and responds well to antibiotic treatment.7 However, erythema migrans is often not observed preceding disseminated Lyme borreliosis manifestations such as neuroborreliosis, Lyme arthritis and Lyme carditis.
Title: What Are the Symptoms of Lyme Disease by Stages?Category: Diseases and ConditionsCreated: 6/17/2020 12:00:00 AMLast Editorial Review: 6/17/2020 12:00:00 AM
(Virginia Tech) With a $661,216 grant from the Steven&Alexandra Cohen Foundation, Brandon Jutras, an assistant professor of biochemistry in the Virginia Tech College of Agriculture and Life Sciences, will study Lyme arthritis, including the cellular component that contributes to it.
(Washington State University) The next time a tick feeds on you, Washington State University researchers hope to make sure persistent arthritis caused by Lyme disease doesn't linger for a lifetime.