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Megan T. WilliamsYan ZhangMark E. PulseRance E. BergMichael S. Allen1Department of Microbiology, Immunology, and Genetics, School of Biomedical Sciences, University of North Texas Health Science Center, Fort Worth, Texas, USA2The Tick-Borne Disease Research Laboratory, University of North Texas Health Science Center, Fort Worth, Texas, USA3Department of Pharmaceutical Sciences, College of Pharmacy, University of North Texas Health Science Center, Fort Worth, Texas, USA, Guy H. Palmer
Infection and Immunity, 22.03.2024
Tilføjet 22.03.2024
BMC Infectious Diseases, 22.03.2024
Tilføjet 22.03.2024
Abstract Background Genetic variation underly inter-individual variation in host immune responses to infectious diseases, and may affect susceptibility or the course of signs and symptoms. Methods We performed genome-wide association studies in a prospective cohort of 1138 patients with physician-confirmed Lyme borreliosis (LB), the most common tick-borne disease in the Northern hemisphere caused by the bacterium Borrelia burgdorferi sensu lato. Genome-wide variants in LB patients—divided into a discovery and validation cohort—were compared to two healthy cohorts. Additionally, ex vivo monocyte-derived cytokine responses of peripheral blood mononuclear cells to several stimuli including Borrelia burgdorferi were performed in both LB patient and healthy control samples, as were stimulation experiments using mechanistic/mammalian target of rapamycin (mTOR) inhibitors. In addition, for LB patients, anti-Borrelia antibody responses were measured. Finally, in a subset of LB patients, gene expression was analysed using RNA-sequencing data from the ex vivo stimulation experiments. Results We identified a previously unknown genetic variant, rs1061632, that was associated with enhanced LB susceptibility. This polymorphism was an eQTL for KCTD20 and ETV7 genes, and its major risk allele was associated with upregulation of the mTOR pathway and cytokine responses, and lower anti-Borrelia antibody production. In addition, we replicated the recently reported SCGB1D2 locus that was suggested to have a protective effect on B. burgdorferi infection, and associated this locus with higher Borrelia burgdorferi antibody indexes and lower IL-10 responses. Conclusions Susceptibility for LB was associated with higher anti-inflammatory responses and reduced anti-Borrelia antibody production, which in turn may negatively impact bacterial clearance. These findings provide important insights into the immunogenetic susceptibility for LB and may guide future studies on development of preventive or therapeutic measures. Trial registration The LymeProspect study was registered with the International Clinical Trials Registry Platform (NTR4998, registration date 2015–02-13).
Læs mere Tjek på PubMedMalte M. Tetens, Lars Haukali Omland, Ram Dessau, Svend Ellermann-Eriksen, Nanna S. Andersen, Charlotte Sværke Jørgensen, Christian Østergaard, Jacob Bodilsen, Kirstine K. Søgaard, Jette Bangsborg, Alex Christian Nielsen, Jens Kjølseth Møller, Ming Chen, Jesper Hastrup Svendsen, Niels Obel, Anne-Mette Lebech
Clinical Microbiology and Infection, 3.02.2024
Tilføjet 3.02.2024
To investigate the short- and long-term risks of atrioventricular block and other cardiac conduction disorders associated with being tested for Borrelia burgdorferi (Bb) antibodies or Bb seropositivity as measures of confounding by indication and Bb infection, respectively.
Læs mere Tjek på PubMedScarlet A. ShifflettFrancisco C. FerreiraJulia GonzálezAlvaro ToledoDina M. FonsecaVincenzo A. Ellis1Department of Entomology and Wildlife Ecology, University of Delaware, Newark, Delaware, USA2Center for Vector Biology, Department of Entomology, Rutgers University, New Brunswick, New Jersey, USA, Guy H. Palmer
Infection and Immunity, 16.12.2023
Tilføjet 16.12.2023
Malte M. Tetens, Lars Haukali Omland, Ram Dessau, Svend Ellermann-Eriksen, Nanna S. Andersen, Charlotte Sværke Jørgensen, Christian Østergaard, Jacob Bodilsen, Kirstine K. Søgaard, Jette Bangsborg, Alex Christian Nielsen, Jens Kjølseth Møller, Ming Chen, Carsten Utoft Niemann, Anne-Mette Lebech, Niels Obel
Clinical Microbiology and Infection, 22.10.2023
Tilføjet 22.10.2023
In a nationwide, matched cohort study, we aimed to investigate risks of hematologic cancers among individuals tested for Borrelia burgdorferi (Bb) antibodies, and among serum Bb seropositive individuals.
Læs mere Tjek på PubMedAndrea M. Kirby, Ellis P. Evans, Samantha J. Bishop, Vett K. Lloyd
PLoS One Infectious Diseases, 14.10.2023
Tilføjet 14.10.2023
by Andrea M. Kirby, Ellis P. Evans, Samantha J. Bishop, Vett K. Lloyd Tick populations are dependent on a complex interplay of abiotic and biotic influences, many of which are influenced by anthropic factors including climate change. Dermacentor variabilis, the wood tick or American dog tick, is a hardy tick species that feeds from a wide range of mammals and birds that can transmit pathogens of medical and agricultural importance. Significant range expansion across North America has been occurring over the past decades;this study documents northwards range expansion in the Canadian Maritime provinces. Tick recoveries from passive surveillance between 2012 and 2021 were examined to assess northward population expansion through Atlantic Canada. At the beginning of this period, D. variabilis was abundant in the most southerly province, Nova Scotia, but was not considered established in the province to the north, New Brunswick. During the 10-year span covered by this study, an increasing number of locally acquired ticks were recovered in discrete foci, suggesting small established or establishing populations in southern and coastal New Brunswick. The pattern of population establishment follows the climate-driven establishment pattern of Ixodes scapularis to some extent but there is also evidence of successful seeding of disjunct populations in areas identified as sub-optimal for tick populations. Dogs were the most common host from which these ticks were recovered, which raises the possibility of human activity, via movement of companion animals, having a significant role in establishing new populations of this species. Dermacentor variabilis is a vector of several pathogens of medical and agricultural importance but is not considered to be a competent vector for Borrelia burgdorferi, the etiological agent of Lyme disease; our molecular analysis of a subset of D. variabilis for both B. burgdorferi and B. miyamotoi did not confirm any with Borrelia. This study spans the initial establishment of this tick species and documents the pattern of introduction, providing a relatively unique opportunity to examine the first stages of range expansion of a tick species.
Læs mere Tjek på PubMedSamir Mechai, Heather Coatsworth, Nicholas H. Ogden
PLoS One Infectious Diseases, 11.10.2023
Tilføjet 11.10.2023
by Samir Mechai, Heather Coatsworth, Nicholas H. Ogden The outer surface protein C (OspC) of the agent of Lyme disease, Borrelia burgdorferi sensu stricto, is a major lipoprotein surface-expressed during early-phase human infections. Antibodies to OspC are used in serological diagnoses. This study explored the hypothesis that serological test sensitivity decreases as genetic similarity of ospC major groups (MGs) of infecting strains, and ospC A (the MG in the strain B31 used to prepare antigen for serodiagnosis assays) decreases. We used a previously published microarray dataset to compare serological reactivity to ospC A (measured as pixel intensity) versus reactivity to 22 other ospC MGs, within a population of 55 patients diagnosed by two-tier serological testing using B. burgdorferi s.s. strain B31 as antigen, in which the ospC MG is OspC A. The difference in reactivity of sera to ospC A and reactivity to each of the other 22 ospC MGs (termed ‘reactivity difference’) was the outcome variable in regression analysis in which genetic distance of the ospC MGs from ospC A was the explanatory variable. Genetic distance was computed for the whole ospC sequence, and 9 subsections, from Neighbour Joining phylogenetic trees of the 23 ospC MGs. Regression analysis was conducted using genetic distance for the full ospC sequence, and the subsections individually. There was a significant association between the reactivity difference and genetic distance of ospC MGs from ospC A: increased genetic distance reduced reactivity to OspC A. No single ospC subsection sequence fully explained the relationship between genetic distance and reactivity difference. An analysis of single nucleotide polymorphisms supported a biological explanation via specific amino acid modifications likely to change protein binding affinity. This adds support to the hypothesis that genetic diversity of B. burgdorferi s.s. (here specifically OspC) may impact serological diagnostic test performance. Further prospective studies are necessary to explore the clinical implications of these findings.
Læs mere Tjek på PubMedMartin StrnadNatalie RudenkoRyan O.M. Regoa Biology Centre CAS, Institute of Parasitology, České Budějovice, Czech Republicb Faculty of Science, University of South Bohemia, Branišovská, Czech Republic
Virulence, 10.10.2023
Tilføjet 10.10.2023
Marc Westerholt, Karen Angeliki Krogfelt, Ram Benny Dessau, Lukas Frans Ocias
Clinical Microbiology and Infection, 26.09.2023
Tilføjet 26.09.2023
Lyme borreliosis (LB) is the most common tick-transmitted infection on the northern hemisphere and is caused by bacteria in the Borrelia burgdorferi sensu lato (Bbsl)-complex. The diagnosis is partially based on serology and clinicians often take follow-up serum samples to look for seroconversion or an increase in IgG-antibody levels. In this registry-based study, we proposed a method for determining actual changes in IgG and examined antibody reactivity and decay.
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