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

Abstract

The influence of immune response gene variations on the development of chronic complications of Q fever is presently unclear. To compare the frequencies of allelic polymorphisms in immune response genes in different Q fever patient groups. Genetic association study. 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. 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. 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.