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- Lindh, Magnus, 1960, et al.
(författare)
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Interleukin 28B Gene Variation at rs12979860 Determines Early Viral Kinetics During Treatment in Patients Carrying Genotypes 2 or 3 of Hepatitis C Virus
- 2011
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Ingår i: Journal of Infectious Diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 203:12, s. 1748-1752
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Tidskriftsartikel (refereegranskat)abstract
- Single-nucleotide polymorphisms upstream of the interleukin 28B (interferon lambda 3) gene (IL28B) strongly influence treatment efficacy in patients carrying hepatitis C virus (HCV) of genotype 1. In patients receiving 12 or 24 weeks of interferon-ribavirin therapy for infection with genotype 2 or 3 (n = 341), we found that rs12979860 strikingly determined the first phase of viral elimination (P < .001). In patients treated for 24 weeks, rs12979860 also predicted the rate of sustained virologic response (P = .02), especially among those with high baseline HCV RNA levels (P = .002) or older than 45 years (P = .01). Patients carrying CCrs12979860 had higher baseline HCV RNA levels (P < .001) and did not, when treated for 12 weeks, achieve sustained virologic response more often than those carrying CTrs1297986 or TTrs1297986. The results indicate that IL28B gene testing may identify patients carrying genotype 2 or 3 who could benefit from extended treatment.
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| 2. |
- Riise, Rebecca E, 1987, et al.
(författare)
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TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses
- 2015
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Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 0022-1767 .- 1550-6606. ; 195:3, s. 1121-1128
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Tidskriftsartikel (refereegranskat)abstract
- Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-gamma production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.
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| 3. |
- Waldenström, Jesper, 1985, et al.
(författare)
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Presence of interferon-lambda, 4, male vender, absent/mild steatosis and low viral load augment antibody levels to hepatitis C virus
- 2021
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Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 0036-5521 .- 1502-7708. ; 56:7, s. 849-854
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Despite recombinant interferon-lambda 4 (IFN-lambda 4) demonstrating anti-viral activity in vitro and the ancestral functional gene (IFNL4) being conserved in all other primates, there has been speculation that IFN-?A may be detrimental in humans. In light of recent rekindled interest in humoral immunity, this study aimed at evaluating the impact of baseline characteristics, including IFNL4, on antibody levels to hepatitis C virus (HCV). Materials and methods: Pretreatment sera from 279 well-characterized North European Caucasians with chronic HCV genotype 2 or 3 infection having undergone liver biopsy were analyzed regarding IFNL4 (rs12979860) and anti-HCV antibody levels using a commercially available assay. Results: Patients producing IFN-lambda 4 had higher signal to cut-off (S/CO) anti-HCV antibody ratios as compared with those lacking IFN-lambda 4 (IFNL4(rs1)(2979860) CT/TT versus CC, p<.0001, Mann-Whitney U-test). Additionally, in univariate analyses S/CO was significantly higher in men than women (p<.001), as well as in patients with absent/mild interface hepatitis (Ishak grade 0-2 versus 3-4, p =.009), and absent/ mild steatosis (grade 0-1 versus 2-3, p=.0005). Also, an inverse correlation with HCV RNA level (r(5) = -0.14, p=.02) was noted. In multivariate analysis IFN-lambda 4, gender, steatosis and viral load remained independently associated. Conclusions: To our knowledge, this is the first report that demonstrates that the ability to produce IFN-lambda 4, in addition to male gender, absent/mild steatosis, and lower viral load, augments antibody levels against HCV. This indicates that IFN-lambda 4 may be associated with T helper cell 2 (Th2) immune skewing, which might have clinical implications beyond HCV infection.
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