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| 2. |
- Glasbey, JC, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 5. |
- Bruggmann, P., et al.
(författare)
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Historical epidemiology of hepatitis C virus (HCV) in selected countries
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 5-33
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Tidskriftsartikel (refereegranskat)abstract
- Chronic infection with hepatitis C virus (HCV) is a leading indicator for liver disease. New treatment options are becoming available, and there is a need to characterize the epidemiology and disease burden of HCV. Data for prevalence, viremia, genotype, diagnosis and treatment were obtained through literature searches and expert consensus for 16 countries. For some countries, data from centralized registries were used to estimate diagnosis and treatment rates. Data for the number of liver transplants and the proportion attributable to HCV were obtained from centralized databases. Viremic prevalence estimates varied widely between countries, ranging from 0.3% in Austria, England and Germany to 8.5% in Egypt. The largest viremic populations were in Egypt, with 6358000 cases in 2008 and Brazil with 2106000 cases in 2007. The age distribution of cases differed between countries. In most countries, prevalence rates were higher among males, reflecting higher rates of injection drug use. Diagnosis, treatment and transplant levels also differed considerably between countries. Reliable estimates characterizing HCV-infected populations are critical for addressing HCV-related morbidity and mortality. There is a need to quantify the burden of chronic HCV infection at the national level.
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| 6. |
- Razavi, H., et al.
(författare)
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The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21:Suppl. 1, s. 34-59
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Tidskriftsartikel (refereegranskat)abstract
- The disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013-2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late-stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver-related deaths from increasing.
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| 7. |
- Wedemeyer, H., et al.
(författare)
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Strategies to manage hepatitis C virus (HCV) disease burden
- 2014
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Ingår i: Journal of Viral Hepatitis. - Hoboken : Wiley-Blackwell. - 1352-0504 .- 1365-2893. ; 21, s. 60-89
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Tidskriftsartikel (refereegranskat)abstract
- The number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV-related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3-5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
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| 8. |
- Andersson, Ida E, 1982-, et al.
(författare)
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Design of glycopeptides used to investigate class II MHC binding and T-Cell responses associated with autoimmune arthritis
- 2011
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 6:3, s. e17881-
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Tidskriftsartikel (refereegranskat)abstract
- The glycopeptide fragment CII259–273 from type II collagen (CII) binds to the murine Aq and human DR4 class II Major Histocompatibility Complex (MHC II) proteins, which are associated with development of murine collagen-induced arthritis (CIA) and rheumatoid arthritis (RA), respectively. It has been shown that CII259–273 can be used in therapeutic vaccination of CIA. This glycopeptide also elicits responses from T-cells obtained from RA patients, which indicates that it has an important role in RA as well. We now present a methodology for studies of (glyco)peptide-receptor interactions based on a combination of structure-based virtual screening, ligand-based statistical molecular design and biological evaluations. This methodology included the design of a CII259–273 glycopeptide library in which two anchor positions crucial for binding in pockets of Aq and DR4 were varied. Synthesis and biological evaluation of the designed glycopeptides provided novel structure-activity relationship (SAR) understanding of binding to Aq and DR4. Glycopeptides that retained high affinities for these MHC II proteins and induced strong responses in panels of T-cell hybridomas were also identified. An analysis of all the responses revealed groups of glycopeptides with different response patterns that are of high interest for vaccination studies in CIA. Moreover, the SAR understanding obtained in this study provides a platform for the design of second-generation glycopeptides with tuned MHC affinities and T-cell responses.
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| 9. |
- Andersson, Ida E., 1982-, et al.
(författare)
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(E)-Alkene and Ethylene Isosteres Substantially Alter the Hydrogen-Bonding Network in Class II MHC Aq/Glycopeptide Complexes and Affect T-Cell Recognition
- 2011
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Ingår i: Journal of the American Chemical Society. - : American Chemical Society. - 0002-7863 .- 1520-5126. ; 133:36, s. 14368-14378
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Tidskriftsartikel (refereegranskat)abstract
- The structural basis for antigen presentation by class II major histocompatibility complex (MHC) proteins to CD4(+) T-cells is important for understanding and possibly treating autoimmune diseases. In the work described in this paper, (E)-alkene and ethylene amide-bond isosteres were used to investigate the effect of removing hydrogen-bonding possibilities from the CII259-270 glycopeptide, which is bound by the arthritis-associated murine A(q) class II MHC protein. The isostere-modified glycopeptides showed varying and unexpectedly large losses of A(q) binding that could be linked to the dynamics of the system. Molecular dynamics (MD) simulations revealed that the backbone of CII259-270 and the A(q) protein are able to form up to 11 hydrogen bonds, but fewer than this number are present at any one time. Most of the strong hydrogen-bond interactions were formed by the N-terminal part of the glycopeptide, i.e., in the region where the isosteric replacements were made. The structural dynamics also revealed that hydrogen bonds were strongly coupled to each other; the loss of one hydrogen-bond interaction had a profound effect on the entire hydrogen-bonding network. The A(q) binding data revealed that an ethylene isostere glycopeptide unexpectedly bound more strongly to A(q) than the corresponding (E)-alkene, which is in contrast to the trend observed for the other isosteres. Analysis of the MD trajectories revealed that the complex conformation of this ethylene isostere was structurally different and had an altered molecular interaction pattern compared to the other A(q)/glycopeptide complexes. The introduced amide-bond isosteres also affected the interactions of the glycopeptide/A(q) complexes with T-cell receptors. The dynamic variation of the patterns and strengths of the hydrogen-bond interactions in the class II MHC system is of critical importance for the class II MHC/peptide/TCR signaling system.
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| 10. |
- Andersson, Ida E., 1982-, et al.
(författare)
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Oxazole-modified glycopeptides that target arthritis-associated class II MHC Aq and DR4 proteins
- 2010
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Ingår i: Organic and biomolecular chemistry. - : RSC Publishing. - 1477-0520 .- 1477-0539. ; 8:13, s. 2931-2940
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Tidskriftsartikel (refereegranskat)abstract
- The glycopeptide CII259-273, a fragment from type II collagen (CII), can induce tolerance in mice susceptible to collagen-induced arthritis (CIA), which is a validated disease model for rheumatoid arthritis (RA). Here, we describe the design and synthesis of a small series of modified CII259-273 glycopeptides with oxazole heterocycles replacing three potentially labile peptide bonds. These glycopeptidomimetics were evaluated for binding to murine CIA-associated A(q) and human RA-associated DR4 class II major histocompatibility complex (MHC) proteins. The oxazole modifications drastically reduced or completely abolished binding to A(q). Two of the glycopeptidomimetics were, however, well tolerated in binding to DR4 and they also induced strong responses by one or two DR4-restricted T-cell hybridomas. This work contributes to the development of an altered glycopeptide for inducing immunological tolerance in CIA, with the long-term goal of developing a therapeutic vaccine for treatment of RA.
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