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Genetic variations in innate immunity genes affect response to Coxiella burnetii and are associated with susceptibility to chronic Q fever.
Jansen, A F M; Schoffelen, T; Bleeker-Rovers, C P; Wever, P C; Jaeger, M; Oosting, M; Adriaans, A; Joosten, L A B; Netea, M G; van Deuren, M; van de Vosse, E.
Afiliación
  • Jansen AFM; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Expert Centre for Q Fever, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: Anne.FM.Jansen@radboudumc.nl.
  • Schoffelen T; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Expert Centre for Q Fever, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Bleeker-Rovers CP; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Expert Centre for Q Fever, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Wever PC; Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, 's-Hertogenbosch, the Netherlands.
  • Jaeger M; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Oosting M; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Adriaans A; Department of Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands.
  • Joosten LAB; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands.
  • Netea MG; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Department for Genomics & Immunoregulation, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany.
  • van Deuren M; Department of Internal Medicine, Radboud University Medical Center, Nijmegen, the Netherlands; Radboud Expert Centre for Q Fever, Radboud University Medical Center, Nijmegen, the Netherlands.
  • van de Vosse E; Department of Infectious Diseases, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address: E.van_de_Vosse@lumc.nl.
Clin Microbiol Infect ; 25(5): 631.e11-631.e15, 2019 May.
Article en En | MEDLINE | ID: mdl-30616015
OBJECTIVES: Chronic Q fever is a persistent infection, mostly of aortic aneurysms, vascular prostheses or damaged heart valves, caused by the intracellular bacterium Coxiella burnetii. Only a fraction of C. burnetii-infected individuals at risk develop chronic Q fever. In these individuals, a defective innate immune response may contribute to the development of chronic Q fever. We assessed whether genetic variations in genes involved in the killing machinery for C. burnetii by macrophages, contribute to the progression to chronic Q fever. METHODS: The prevalence of 66 single nucleotide polymorphisms (SNPs) in 31 genes pivotal in phagolysosomal maturation, bacterial killing and autophagy, was determined in 173 chronic Q fever patients and 184 controls with risk factors for chronic Q fever and serological evidence of a C. burnetii infection. Associations were detected with univariate logistic regression models. To assess the effect of these SNPs on innate responses to C. burnetii, the C. burnetii-induced cytokine production and basal reactive oxygen species production of healthy volunteers was determined. RESULTS: RAB7A (rs13081864) and P2RX7 loss-of-function SNP (rs3751143) were more common in chronic Q fever patients than in controls. RAB5A (rs8682), P2RX7 gain-of-function SNP (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) were more common in controls. In healthy volunteers, RAB7A (rs13081864) and MAP1LC3A (rs1040747) influenced the C. burnetii-induced cytokine production. RAB7A (rs13081864) modulated basal reactive oxygen species production. CONCLUSIONS: RAB7A (rs13081864) and P2RX7 (rs3751143) are associated with the development of chronic Q fever, whereas RAB5A (rs8682), P2RX7 (rs1718119), MAP1LC3A (rs1040747) and ATG5 (rs2245214) may have protective effects.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Q / Coxiella burnetii / Predisposición Genética a la Enfermedad / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Microbiol Infect Asunto de la revista: DOENCAS TRANSMISSIVEIS / MICROBIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Fiebre Q / Coxiella burnetii / Predisposición Genética a la Enfermedad / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Clin Microbiol Infect Asunto de la revista: DOENCAS TRANSMISSIVEIS / MICROBIOLOGIA Año: 2019 Tipo del documento: Article Pais de publicación: Reino Unido