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https://infmed.dk/nyheder-udefra?rss_filter=borrelia&setpoint=100290#101107
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https://infmed.dk/nyheder-udefra?rss_filter=borrelia&setpoint=100290#101082
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2 emner vises.
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).
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