Martin Singer1, Wei Li2, Servaas A Morré3, Sander Ouburg1, Stanley M Spinola4. 1. Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam. 2. Department of Microbiology and Immunology. 3. Laboratory of Immunogenetics, Department of Medical Microbiology and Infection Control, VU University Medical Center, Amsterdam Institute for Public Health Genomics, Department of Genetics and Cell Biology, School for Oncology and Developmental Biology, Faculty of Health, Medicine and Life Sciences, Maastricht University, The Netherlands. 4. Department of Microbiology and Immunology Departments of Medicine Pathology and Laboratory Medicine Center for Immunobiology, Indiana University School of Medicine, Indiana University, Indianapolis.
Abstract
BACKGROUND: In humans inoculated with Haemophilus ducreyi, there are host effects on the possible clinical outcomes-pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection. METHODS: DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ(2) tests for trend and logistic regression analyses were performed on the data. RESULTS: In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 -2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype. CONCLUSIONS: Variations in TLR9 and IL10 are associated with the outcome of H. ducreyi infection.
BACKGROUND: In humans inoculated with Haemophilus ducreyi, there are host effects on the possible clinical outcomes-pustule formation versus spontaneous resolution of infection. However, the immunogenetic factors that influence these outcomes are unknown. Here we examined the role of 14 single-nucleotide polymorphisms (SNPs) in 7 selected pathogen-recognition pathways and cytokine genes on the gradated outcomes of experimental infection. METHODS: DNAs from 105 volunteers infected with H. ducreyi at 3 sites were genotyped for SNPs, using real-time polymerase chain reaction. The participants were classified into 2 cohorts, by race, and into 4 groups, based on whether they formed 0, 1, 2, or 3 pustules. χ(2) tests for trend and logistic regression analyses were performed on the data. RESULTS: In European Americans, the most significant findings were a protective association of the TLR9 +2848 GG genotype and a risk-enhancing association of the TLR9 TA haplotype with pustule formation; logistic regression showed a trend toward protection for the TLR9 +2848 GG genotype. In African Americans, logistic regression showed a protective effect for the IL10 -2849 AA genotype and a risk-enhancing effect for the IL10 AAC haplotype. CONCLUSIONS: Variations in TLR9 and IL10 are associated with the outcome of H. ducreyiinfection.
Authors: Wei Li; Klara Tenner-Racz; Paul Racz; Diane M Janowicz; Kate R Fortney; Barry P Katz; Stanley M Spinola Journal: J Infect Dis Date: 2010-06-15 Impact factor: 5.226
Authors: Brigit A de Jong; Rudi G J Westendorp; Joyce Eskdale; Bernard M J Uitdehaag; Tom W J Huizinga Journal: Hum Immunol Date: 2002-04 Impact factor: 2.850
Authors: S Ouburg; J M Lyons; J A Land; J E den Hartog; J S A Fennema; H J C de Vries; C A Bruggeman; J I Ito; A S Peña; P S J Lundberg; S A Morré Journal: Drugs Today (Barc) Date: 2009-11 Impact factor: 2.245
Authors: J E den Hartog; J M Lyons; S Ouburg; J S A Fennema; H J C de Vries; C A Bruggeman; J I Ito; A S Peña; J A Land; S A Morré Journal: Drugs Today (Barc) Date: 2009-11 Impact factor: 2.245