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- Flach, Carl-Fredrik, 1977, et al.
(författare)
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Pro-inflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. : Immune correlates to H. pylori protection
- 2011
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Ingår i: Infection and immunity. - 1098-5522. ; 79:2, s. 879-886
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Tidskriftsartikel (refereegranskat)abstract
- CD4(+) T cells have been shown to be essential for vaccine-induced protection against Helicobacter pylori infection in mice. Less is known about relative contributions of individual cell subpopulations, such as TH1 and TH17 cells, and their associated cytokines. The aim of the present study was to find immune correlates to vaccine-induced protection and further study their role in protection against H. pylori infection. Immunized and unimmunized mice were challenged with H. pylori and immune responses were compared. Vaccine-induced protection was assessed by measuring H. pylori colonization in the stomach. Gastric gene expression of TH1- and/or TH17-associated cytokines was analyzed by quantitative PCR and contributions of individual cytokines to protection were evaluated by antibody-mediated in vivo neutralization. By analyzing immunized and unimmunized mice a significant inverse correlation could be demonstrated between levels of interleukin (IL)-12p40, tumor necrosis factor α (TNF), interferon γ (IFNγ) and IL-17 gene expression and number of H. pylori in the stomach of individual animals after challenge. In a kinetic study, up-regulation of TNF, IFNγ and IL-17 coincided with vaccine-induced protection 7 days after H. pylori challenge and was sustained for at least 21 days. In vivo neutralization of these cytokines during the effector phase of the immune response revealed a significant role for IL-17, but not for IFNγ or TNF, in vaccine-induced protection. In conclusion, although both TH1- and TH17-associated gene expression in the stomach correlate with vaccine-induced protection against H. pylori infection, our study indicates that mainly TH17 effector mechanisms are of critical importance to protection.
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| 2. |
- Meisgen, Sabrina, et al.
(författare)
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The HLA locus contains novel foetal susceptibility alleles for congenital heart block with significant paternal influence
- 2014
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 275:6, s. 640-651
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The main aim of this study was to identify foetal susceptibility genes on chromosome six for Ro/SSA autoantibody-mediated congenital heart block.SUBJECTS AND DESIGN: Single nucleotide polymorphism (SNP) genotyping of individuals in the Swedish Congenital Heart Block (CHB) study population was performed. Low-resolution HLA-A, -Cw and -DRB1 allele typing was carried out in 86 families comprising 339 individuals (86 Ro/SSA autoantibody-positive mothers, 71 fathers, 87 CHB index cases, and 95 unaffected siblings).RESULTS: A case-control comparison between index cases and population-based out-of-study controls (n=1710) revealed association of CHB with 15 SNPs in the 6p21.3 MHC locus at a chromosome-wide significance of p<2.59×10(-6) (OR 2.21-3.12). In a family-based analysis of association of SNP markers as well as distinct MHC class I and II alleles with CHB, HLA-DRB1*04 and HLA-Cw*05 variants were significantly more frequently transmitted to affected individuals (p<0.03 and p<0.05, respectively), while HLA-DRB1*13 and HLA-Cw*06 variants were significantly less often transmitted to affected children (p<0.04 and p<0.03). We further observed marked association of increased paternal (but not maternal) HLA-DRB1*04 transmission to affected offspring (p<0.02).CONCLUSIONS: HLA-DRB1*04 and HLA-Cw*05 were identified as novel foetal HLA allele variants that confer susceptibility to CHB in response to Ro/SSA autoantibody exposure, while DRB1*13 and Cw*06 emerged as protective alleles. Additionally, we demonstrated a paternal contribution to foetal susceptibility to CHB for the first time.
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