Immune response genes in the post Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever

K. Helbig, R. Harris, Jonathan Geoffrey Ayres, H. Dunckley, A. Lloyd

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    Background: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear.

    Aim: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups.

    Design: Genetic association study.

    Methods: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population.

    Results: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels.

    Discussion: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

    Original languageEnglish
    Pages (from-to)565-574
    Number of pages9
    JournalQJM
    Volume98
    Issue number8
    DOIs
    Publication statusPublished - Aug 2005

    Keywords

    • TUMOR-NECROSIS-FACTOR
    • LONG-TERM PERSISTENCE
    • COXIELLA-BURNETII
    • INTERFERON-GAMMA
    • TNF-RECEPTOR
    • INTERLEUKIN-10
    • ASSOCIATION
    • HLA
    • DYSREGULATION
    • POLYMORPHISM

    Cite this

    Immune response genes in the post Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever. / Helbig, K.; Harris, R.; Ayres, Jonathan Geoffrey; Dunckley, H.; Lloyd, A.

    In: QJM, Vol. 98, No. 8, 08.2005, p. 565-574.

    Research output: Contribution to journalArticle

    Helbig, K. ; Harris, R. ; Ayres, Jonathan Geoffrey ; Dunckley, H. ; Lloyd, A. / Immune response genes in the post Q-fever fatigue syndrome, Q fever endocarditis and uncomplicated acute primary Q fever. In: QJM. 2005 ; Vol. 98, No. 8. pp. 565-574.
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    abstract = "Background: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear.Aim: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups.Design: Genetic association study.Methods: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population.Results: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels.Discussion: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.",
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    AU - Ayres, Jonathan Geoffrey

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    AU - Lloyd, A.

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    N2 - Background: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear.Aim: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups.Design: Genetic association study.Methods: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population.Results: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels.Discussion: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

    AB - Background: The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear.Aim: To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups.Design: Genetic association study.Methods: We measured the frequencies of immune response gene variants in: (i) an expanded group of 31 post-Q-fever fatigue patients (QFS); (ii) 22 Q fever endocarditis patients (QFE); and (iii) 22 patients who made an uncomplicated recovery from their initial attack of primary acute Q fever, comparing them with various standard control panels from the general population.Results: There were significant differences between the three Q fever groups. QFS patients differed from both QFE and uncomplicated patients and controls in the frequency of carriage of HLA-DRB1*11 and of the 2/2 genotype of the interferon-gamma intron1 microsatellite. Carriage of the HLA DRB1*11 allele was associated with reduced interferon-gamma and IL-2 responses from PBMC stimulated with ligand in short-term culture. QFE showed differences in the IL-10 promoter microsatellites R and G and had higher frequencies of the TNF-alpha receptor II 196R polymorphism. Q fever patients who had made an uncomplicated recovery differed from those with QFS or QFE, but were not significantly different in allelic frequencies to the control panels.Discussion: These immunogenetic differences support the concept of different immune states in chronic Q fever, determined by genetic variations in host immune responses, rather than by solely properties of Coxiella burnetii.

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    KW - TNF-RECEPTOR

    KW - INTERLEUKIN-10

    KW - ASSOCIATION

    KW - HLA

    KW - DYSREGULATION

    KW - POLYMORPHISM

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