| 1. |
- Iversen, AKN, et al.
(author)
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Limited protective effect of the CCR5 Delta 32/CCR5 Delta 32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus
- 2003
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In: Journal of Infectious Diseases. - 1537-6613. ; 187:2, s. 215-225
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Journal article (peer-reviewed)abstract
- The relationship among CCR5 genotype, cytomegalovirus infection, and disease progression and death was studied among 159 human immunodeficiency virus (HIV)-infected patients with hemophilia. One patient (0.6%) had the CCR5Delta32/CCR5Delta32 genotype (which occurs in similar to2% of the Scandinavian population) and a rapid disease course. His HIV V3 region contained genotypic features attributable to X4 virus and resembled functionally verified X4 virus and virus from patients treated with a CD4 cell-stimulating drug, tucaresol. Age-related differences in disease progression rate and survival time were seen for CCR5/CCR5 patients. Surprisingly, no protective effect of the CCR5/CCR5Delta32 genotype on disease progression or survival was seen for children but was evident for adults. Age group-related immunologic differences might explain this variation, and transmission route and/or viral phenotype variation within donor virus may be related to the limited protection of the CCR5Delta32/ CCR5Delta32 genotype. Sequence comparisons indicate that X4 virus can be selected in vivo due to either absence of CCR5 receptors or relative increase of CXCR4 receptors.
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| 4. |
- Hindy, George, et al.
(author)
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Increased soluble urokinase plasminogen activator levels modulate monocyte function to promote atherosclerosis
- 2022
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In: Journal of Clinical Investigation. - 0021-9738. ; 132:24, s. 1-14
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Journal article (peer-reviewed)abstract
- People with kidney disease are disproportionately affected by atherosclerosis for unclear reasons. Soluble urokinase plasminogen activator receptor (suPAR) is an immune-derived mediator of kidney disease, levels of which are strongly associated with cardiovascular outcomes. We assessed suPAR’s pathogenic involvement in atherosclerosis using epidemiologic, genetic, and experimental approaches. We found serum suPAR levels to be predictive of coronary artery calcification and cardiovascular events in 5,406 participants without known coronary disease. In a genome-wide association meta-analysis including over 25,000 individuals, we identified a missense variant in the plasminogen activator, urokinase receptor (PLAUR) gene (rs4760), confirmed experimentally to lead to higher suPAR levels. Mendelian randomization analysis in the UK Biobank using rs4760 indicated a causal association between genetically predicted suPAR levels and atherosclerotic phenotypes. In an experimental model of atherosclerosis, proprotein convertase subtilisin/kexin–9 (Pcsk9) transfection in mice overexpressing suPAR (suPARTg) led to substantially increased atherosclerotic plaques with necrotic cores and macrophage infiltration compared with those in WT mice, despite similar cholesterol levels. Prior to induction of atherosclerosis, aortas of suPARTg mice excreted higher levels of CCL2 and had higher monocyte counts compared with WT aortas. Aortic and circulating suPARTg monocytes exhibited a proinflammatory profile and enhanced chemotaxis. These findings characterize suPAR as a pathogenic factor for atherosclerosis acting at least partially through modulation of monocyte function.
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| 6. |
- Eugen-Olsen, J, et al.
(author)
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The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau
- 2002
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In: The International Journal of Tuberculosis and Lung Disease. - 1815-7920. ; 6:8, s. 686-692
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Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate whether the serum level of soluble urokinase plasminogen activator receptor (suPAR) carries prognostic information in individuals infected with Mycobacterium tuberculosis. DESIGN: suPAR was measured by ELISA in 262 individuals at the time of enrolment into a cohort based on suspicion of active tuberculosis and in 101 individuals after 8 months of follow-up. RESULTS: The suPAR levels were elevated in patients with active TB compared to TB-negative individuals (P < 0.001). suPAR levels were highest in patients positive for TB on direct microscopy (n = 84, median suPAR 3.17 ng/ml, P < 0.001), followed by patients negative on direct microscopy but culture positive (n = 35, median suPAR 2.41 ng/ml, P = 0.005) and by patients diagnosed on clinical grounds (n = 63, median suPAR 2.13 ng/ml, P = 0.06) compared to 64 TB-negative individuals (median suPAR 1.73 ng/ml). During the 8-month treatment period, 23 TB cases died. In a multivariate Cox model controlling for HIV status, age, sex, CD4 count and type of TB diagnosis, the mortality increase per ng suPAR was 1.25 (95%CI 1.12-1.40). After treatment, suPAR levels had decreased to the levels of TB-negative individuals. CONCLUSIONS: suPAR levels are elevated in TB patients and associated with mortality. Furthermore, suPAR may be a potential marker of treatment efficacy.
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| 8. |
- Knudsen, TB, et al.
(author)
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Predictive value of soluble haemoglobin scavenger receptor CD163 serum levels for survival in verified tuberculosis patients
- 2005
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In: Clinical Microbiology and Infection. - : Elsevier BV. - 1469-0691 .- 1198-743X. ; 11:9, s. 730-735
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Journal article (peer-reviewed)abstract
- Pre-treatment serum levels of sCD163 were measured in a cohort of 236 suspected tuberculosis (TB) cases from Guinea-Bissau, with a median follow-up period of 3.3 years (range 0-6.4 years). In 113 cases, the diagnosis of TB was verified by positive sputum microscopy and/or culture. Among the verified TB cases, a decreased survival rate was found in 27 patients with sCD163 levels above the upper reference limit (3.95 mu g/mL). The difference in survival was significant during TB treatment (log rank, p < 0.02) and after long-term follow-up (log rank, p < 0.001). The decrease in survival rate during TB treatment remained significant in a multivariate Cox model controlling for human immunodeficiency virus (HIV) status, age and gender, with a mortality increase of 1.19 (95% CI, 1.04-1.36) per mu g of sCD163, and a hazard ratio (HR) for sCD163 levels above the upper reference limit of 4.18 (95% CI, 1.06-16.4). The difference was not significant after excluding patients with concomitant HIV-1 and HIV-2 infection in Kaplan-Meier analyses (log rank, p 0.11). In contrast, the difference in survival remained significant in Kaplan-Meier analyses after long-term follow-up, even after excluding patients with concomitant HIV-1 and HIV-2 infection (log rank, p 0.002). In the Cox model, the mortality increase per mu g of sCD163 was 1.27 (95% CI, 1.14-1.40), with an HR for elevated sCD163 levels of 2.85 (95% CI, 1.44-5.63). The HRs for concomitant HIV-1 and HIV-2 infection were 6.92 (95% CI, 3.28-14.58) and 2.48 (95% CI, 1.09-5.67), respectively. Thus, sCD163 levels appeared to be an independent predictor of survival in verified TB patients.
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