| 1. |
- Babacic, Haris, et al.
(författare)
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Comprehensive proteomics and meta-analysis of COVID-19 host response
- 2023
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Ingår i: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- COVID-19 is characterised by systemic immunological perturbations in the human body, which can lead to multi-organ damage. Many of these processes are considered to be mediated by the blood. Therefore, to better understand the systemic host response to SARS-CoV-2 infection, we performed systematic analyses of the circulating, soluble proteins in the blood through global proteomics by mass-spectrometry (MS) proteomics. Here, we show that a large part of the soluble blood proteome is altered in COVID-19, among them elevated levels of interferon-induced and proteasomal proteins. Some proteins that have alternating levels in human cells after a SARS-CoV-2 infection in vitro and in different organs of COVID-19 patients are deregulated in the blood, suggesting shared infection-related changes.The availability of different public proteomic resources on soluble blood proteome alterations leaves uncertainty about the change of a given protein during COVID-19. Hence, we performed a systematic review and meta-analysis of MS global proteomics studies of soluble blood proteomes, including up to 1706 individuals (1039 COVID-19 patients), to provide concluding estimates for the alteration of 1517 soluble blood proteins in COVID-19. Finally, based on the meta-analysis we developed CoViMAPP, an open-access resource for effect sizes of alterations and diagnostic potential of soluble blood proteins in COVID-19, which is publicly available for the research, clinical, and academic community. Baba & ccaron;ic et al. performed systematic analyses of blood proteins in COVID-19 patients through mass-spectrometry proteomics, showing that a large part of the soluble blood proteome is altered. The authors then developed an open-access resource, CoViMAPP, for meta-analysis of MS proteomics studies of COVID-19 patients.
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| 2. |
- Gredmark-Russ, Sara, et al.
(författare)
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Active cytomegalovirus infection in aortic smooth muscle cells from patients with abdominal aortic aneurysm
- 2009
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Ingår i: Journal of Molecular Medicine. - : Springer Science and Business Media LLC. - 0946-2716 .- 1432-1440. ; 87:4, s. 347-356
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Tidskriftsartikel (refereegranskat)abstract
- Cytomegalovirus (CMV) is associated with atherosclerosis and transplant vascular sclerosis. The aim of this study was to explore the hypothesis that active CMV infection in the vessel wall could be associated with abdominal aortic aneurysm (AAA). We examined the prevalence of CMV in AAA specimens from 22 patients undergoing surgery and, in five cases, characterized the function of smooth muscle cells (SMCs) from the aneurysm in vitro. Twenty-one (95%) of the 22 AAA specimens were CMV positive by a polymerase chain reaction assay, in situ hybridization, or a highly sensitive immunohistochemical staining technique. No positive cells were found in aortas from three CMV-seronegative organ donor cadavers. CMV immediate-early and late antigens were expressed in SMCs in the lesions and were associated with 5-lipoxygenase (5-LO) expression. CMV-positive intimal SMCs migrated 6.6 +/- 1.5 times more efficiently than CMV-negative medial SMCs (p < 0.05). In vitro CMV infection of medial SMCs resulted in a 3.2 +/- 1.2 times increase in migration (p < 0.05). The intimal migration was significantly inhibited by antibodies against basic fibroblast growth factor (bFGF; p < 0.05) in a dose-dependent fashion. Antibodies against platelet-derived growth factor (PDGF)-AB, insulin-like growth factor 1, vascular endothelial growth factor (VEGF), RANTES, monocyte chemoattractant protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1alpha, or interleukin-1beta did not significantly affect intimal SMC migration. However, intimal and medial SMCs secreted similar amounts of bFGF, MCP-1, MIP-1alpha, RANTES, PDGF-AB, PDGF-BB, epidermal growth factor, and VEGF. CMV infection in vitro of intimal and medial cells did not result in significant changes of bFGF or MCP-1 secretion. Since CMV infection can affect several functional parameters in SMCs, including several key factors in infected SMCs, our findings provide support for the hypothesis that CMV contributes to the pathogenesis of abdominal aortic aneurysm.
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| 3. |
- Hansson, Karin, et al.
(författare)
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Tick-borne encephalitis (TBE) vaccine failures : A ten-year retrospective study supporting the rationale for adding an extra priming dose in individuals from the age of 50 years
- 2020
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Ingår i: Clinical Infectious Diseases. - : Oxford University Press. - 1058-4838 .- 1537-6591. ; 70:2, s. 245-251
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Southern Sweden is endemic for tick borne encephalitis (TBE), with Stockholm County as one of the high-risk areas. The aim of this study was to describe cases of vaccine failures, and to optimize future vaccination recommendations.METHODS: Patients with TBE were identified in the notification database at the Department of Communicable Disease Control and Prevention in the county of Stockholm during 2006-2015. Vaccine failure was defined as TBE despite adherence to the recommended vaccination schedule with at least two doses. Clinical data were extracted from medical records.RESULTS: A total of 1004 TBE cases were identified, 53 (5%) were defined as vaccine failures. In this latter group the median age was 62 years (6-83). Forty-three (81%) patients were over 50 years of age and two were children. Approximately half of the patients had comorbidities with diseases affecting the immune system accounting for 26% of all cases.Vaccine failures following the third or fourth vaccine dose accounted for 36 (68%) of the patients. Severe and moderate TBE disease affected 81% of the cases.CONCLUSION: To our knowledge, this is the largest documented cohort of TBE-vaccine failures. Vaccine failure after five TBE-vaccine doses is rare. Our data provides rationale for adding an extra priming dose to the age group 50 years and older.
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| 4. |
- Varnaitė, Renata, et al.
(författare)
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Deaths from Tick-Borne Encephalitis, Sweden
- 2022
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Ingår i: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 28:7, s. 1471-1474
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Tidskriftsartikel (refereegranskat)abstract
- We assessed standardized mortality ratio in tick-borne encephalitis (TBE) in Sweden, 2004-2017. Standardized mortality ratio for TBE was 3.96 (95% CI 2.55-5.90); no cases in patients <40 years of age were fatal. These results underscore the need for further vaccination efforts in populations at risk for TBE.
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| 5. |
- Varnaite, Renata, et al.
(författare)
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Magnitude and Functional Profile of the Human CD4(+) T Cell Response throughout Primary Immunization with Tick-Borne Encephalitis Virus Vaccine
- 2020
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Ingår i: Journal of Immunology. - : AMER ASSOC IMMUNOLOGISTS. - 0022-1767 .- 1550-6606. ; 204:4, s. 914-922
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Tidskriftsartikel (refereegranskat)abstract
- Tick-borne encephalitis (TBE) is a viral infection of the CNS caused by TBE virus. With no specific treatment available, the only protection is a formalin-inactivated whole virus vaccine. Primary immunization with European TBE vaccines, as recommended by the manufacturers, consists of three vaccine doses administered within a 1-y period. Protection from vaccination is believed to be mediated by Abs, yet T cells may also have a protective role. We set out to characterize the human CD4(+) T cell response throughout primary TBE immunization. The responses were evaluated before vaccination and 1 mo after each vaccine dose. A heterogeneous magnitude of CD4(+) T cell-mediated memory responses was observed in regard to lymphoblast expansion and cytokine production (IFN-gamma, IL-2, and TNF), with the highest median magnitude detected after the second dose of vaccine. Stimulation with an overlapping peptide library based on structural TBE virus proteins E and C revealed that CD4(+) T cells concomitantly producing IL-2 and TNF dominated the responses from vaccinees after each vaccine dose, whereas a control cohort of TBE patients responded mainly with all three cytokines. CD107a expression was not upregulated upon peptide stimulation in the vaccinees. However, CD154 (CD40L) expression on cytokine-positive memory CD4(+) T cells significantly increased after the second vaccine dose. Taken together, TBE vaccination induced CD4(+) T cell responses dominated by IL-2 and TNF production together with CD154 upregulation and a lower IFN-gamma response compared with TBE patients. This response pattern was consistent after all three doses of TBE vaccine.
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