Abstract
Acute primary Q fever is followed by various chronic sequelae. These include subacute Q fever endocarditis, granulomatous reactions in various organs or a prolonged debilitating post-infection fatigue syndrome (QFS). The causative organism, Coxiella burnetii, persists after an initial infection. The differing chronic outcomes may reflect variations within cytokine and accessory immune control genes which affect regulation of the level of persistence. As a preliminary test of the concept we have genotyped QFS patients and controls for gene variants spanning 15 genes and also examined HLA-B and DR frequencies. QFS patients exhibited a significantly increased frequency of HLA-DR-11 compared with controls and also significant differences in allelic variant frequencies within the NRAMP, and IFNγ genes. These results indicate a possible genetic role in the expression of overt chronic Q fever. Further studies will be undertaken to increase sample sizes, to survey other forms of chronic Q fever and to examine Q fever patients who have recovered without sequelae.
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References
Dellacasagrade J, Capo C, Raoult D, Mege JL . IFNγ mediated control of Coxiella brunetii survival in monocytes: the role of cell apoptosis and TNF. J Immunol 1999; 162: 2298–2365.
Harris RJ, Storm PA, Lloyd A, Arens M, Marmion BP . Long-term persistence of Coxiella burnetii in the host after primary Q fever. Epidemiol Infect 2000; 124: 543–549.
Marmion BP, Shannon M, Maddocks I, Storm P, Pentilla IA . Protracted debility and fatigue after acute Q fever. Lancet 1996; 346: 977–978.
Pentilla IA, Harris RJ, Storm P, Haynes D, Worswick DA, Marmion BP . Cytokine dysregulation in the post Q fever debility and fatigue syndrome. Q J Med 1998; 91: 549–560.
Koster FT, Williams JC, Goodwin JS . Cellular immunity in Q fever: specific lymphocyte unresponsiveness in Q fever endocarditis. J Infect Dis 1985; 152: 1283–1289.
Koster FT, Williams JC, Goodwin JS . Cellular immunity in Q fever: modulation of responsiveness by a suppressor T cell-monocyte circuit. J Immunol 1985; 135: 1067–1072.
Ghigo E, Capo C, Amirayan N, Raoult D, Mege J . The 75-kD tumour necrosis factor (TNF) receptor is specifically regulated in monocytes during Q fever endocarditis. Clin Exp Immunol 2000; 121: 295–301.
Ghigo E, Capo C, Raoult D, Mege JL . Interleukin-10 stimulates Coxiella burnetii replication in human monocytes through tumor necrosis factor down-modulation: role in microbicidal defect of Q fever. Infect Immun 2001; 69: 2345–2352.
Peacock MG, Philip RN, Williams JC, Faulkner RS . Serological evaluation of Q fever in humans: enhanced phase I immunoglobulins G and A are diagnostic for Q fever endocarditis. Infect Immun 1983; 41: 1089–1098.
Hill A . The immunogenetics of human infectious diseases. Annu Rev Immunol 1998; 16: 593–617.
Schork NJ . Genetics of complex disease: approaches, problems, and solutions. Am J Respir Crit Care Med 1997; 156: S103–S109.
McNicholl JM, Downer MV, Udhayakumar V, Alper CA, Swerdlow DL . Host–pathogen interactions in emerging and re-emerging infectious diseases: a genomic perspective of tuberculosis, malaria, human immunodeficiency virus infection, hepatitis B, and cholera. Annu Rev Public Health 2000; 21: 15–46.
Marquet S, Schurr E . Genetics of susceptibility to infectious diseases: tuberculosis and leprosy as examples. Drug Metab Disposition 2001; 29: 479–483.
Izzo AA, Marmion BP . Variation in interferon-gamma responses to Coxiella burnetii antigens with lymphocytes from vaccinated or naturally infected subjects. Clin Exp Immunol 1993; 94: 507–515.
Liu J, Fujiwara TM, Buu NT, Sanchez FO, Cellier M, Paradis AJ et al. Identification of polymorphisms and sequence variants in the human homologue of the mouse natural resistance-associated macrophage protein gene. Am J Hum Genet 1995; 56: 845–853.
Buyse I, Decorte R, Baens M, Cuppens H, Semana G, Emonds MP et al. Rapid DNA typing of class II HLA antigens using polymerase chain reaction and reverse dot blot hybridization. Tissue Antigens 1993; 41: 1–14.
Mullighan CG, Marshall SE, Bunce M, Welsh KI . Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency. Genes Immun 1999; 1: 137–148.
Awad M, Pravica V, Perrey C, Gamel AE, Yonan N, Sinnot PJ et al. CA repeat allele polymorphism in the first intron of the human interferon-γ gene is associated with lung allograft fibrosis. Hum Immnol 1999; 60: 343–346.
Buschman E, Skamene E . From bcg/Ish/ity to Nrampl: three decades of search and research. Drug Metab Disposition 2001; 29: 471–473.
Bellamy R, Ruwende C, Phil D, Corrah T, McAdam K, Whittle HC et al. Variations in the NRAMP1 gene and susceptibility to tuberculosis in west Africans. N Engl J Med 1998; 338: 640–644.
Mitra DK, Rajalingam R, Taneja V, Bhattacharyya BC, Mehra NK . HLA-DR polymorphism modulates the cytokine profile of Mycobacterium leprae HSP-reactive CD4+ T cells. Clin Immunol Immunopathol 1997; 82: 60–67.
Hurley CK, Steiner N . Differences in peptide binding of DR11 and DR13 microvariants demonstrate the power of minor variation in generating DR functional diversity. Hum Immunol 1995; 43: 101–112.
Hendel H, Caillat-Zucman S, Lebuanec H, Carrington M, O'Brien S, Andrieu J-M et al. New class I and II HLA alleles strongly associated with opposite patterns of progression to AIDS. J Immunol 1999; 162: 6942–6946.
Zavaglia C, Martinetti M, Silini E, Bottelli R, Daielli C, Asti M et al. Association between HLA class II alleles and protection from or susceptibility to Chronic hepatitis C. J Hepatol 1997; 28: 1–7.
Pravica V, Asderakis A, Perrey C, Hajeer A, Sinnott PJ, Hutchinson IV . In vitro production of IFNγ correlates with CA repeat allele polymorphism in the human IFNγ gene. Eur J Immunogenet 1999; 26: 1–3.
Jouanguy E, Altare F, Lamhanedis Revy P, Emile JF, Newport M et al. Interferon-γ deficiency in an infant with fatal bacillie Calmette-Guerin infection. N Engl J Med 1996; 335: 1956–1961.
Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, Williamson R et al. A mutation in the interferon -γ receptor gene and susceptibility to mycobacterial infection. N Engl J Med 1996; 335: 1941–1949.
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Study supported with grant from Meat and Livestock Australia Ltd. Dr. Adrian Esterman provided appreciated statistical advice.
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Helbig, K., Heatley, S., Harris, R. et al. Variation in immune response genes and chronic Q fever. Concepts: preliminary test with post-Q fever fatigue syndrome. Genes Immun 4, 82–85 (2003). https://doi.org/10.1038/sj.gene.6363912
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DOI: https://doi.org/10.1038/sj.gene.6363912
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