| 1. |
- Iglesias, Maria Jesus, et al.
(författare)
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Elevated plasma complement factor H related 5 protein is associated with venous thromboembolism
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Venous thromboembolism (VTE) is a common, multi-causal disease with potentially serious short- and long-term complications. In clinical practice, there is a need for improved plasma biomarker-based tools for VTE diagnosis and risk prediction. Here we show, using proteomics profiling to screen plasma from patients with suspected acute VTE, and several case-control studies for VTE, how Complement Factor H Related 5 protein (CFHR5), a regulator of the alternative pathway of complement activation, is a VTE-associated plasma biomarker. In plasma, higher CFHR5 levels are associated with increased thrombin generation potential and recombinant CFHR5 enhanced platelet activation in vitro. GWAS analysis of ~52,000 participants identifies six loci associated with CFHR5 plasma levels, but Mendelian randomization do not demonstrate causality between CFHR5 and VTE. Our results indicate an important role for the regulation of the alternative pathway of complement activation in VTE and that CFHR5 represents a potential diagnostic and/or risk predictive plasma biomarker.
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| 2. |
- Laky, Markus, et al.
(författare)
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Serum levels of 25-hydroxyvitamin D are associated with periodontal disease
- 2017
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Ingår i: Clinical Oral Investigations. - : Springer. - 1432-6981 .- 1436-3771. ; 21:5, s. 1553-1558
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Vitamin D plays an essential role in bone metabo- lism as well as in immunity. Hence, it might affect the devel- opment and extent of periodontal disease. The aim of this study was the assessment of 25-hydroxyvitamin D (25(OH)D) status in periodontal disease. Materials and methods Twenty-nine patients with severe periodontal disease and 29 healthy volunteers were recruited in this case-control-study. Serum 25(OH)D levels, Periodontal Probing Depth (PPD), Clinical Attachment Level (CAL), Bleeding on Probing (BOP), Body Mass Index (BMI), and current smoking status and smoking history (packyears) were assessed in all participants. Serum 25(OH)D levels were com- pared between controls and cases. Multivariable logistic regression was used to determine the odds ratio (OR) and 95 % confidence interval (CI) for periodontal disease in 25(OH)D deficient probands. Results Patients with periodontal disease presented a signifi- cantly higher proportion of deficient 25(OH)D levels (i.e., <50 nmol/l) compared to healthy controls (48 vs. 14 % respec- tively). The adjusted OR for periodontal disease with vitamin D deficiency was 1.5 (95 % CI, 1.13–1.98). No correlation between serum 25(OH)D levels and CAL, PPD, and BOP in the group with periodontal disease was found. Conclusions In this case-control-study 25(OH)D deficiency is significantly associated with periodontal disease. Clinical relevance The assessment of vitamin D levels in pa- tients presenting with periodontal disease seems advisable, as vitamin D deficiency might be involved in the onset and pro- gression of periodontal disease.
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| 3. |
- Waltraud, Schrottmaier, et al.
(författare)
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Activation of circulating platelets leads to innate-like delivery of potent antiviral antibodies
- 2017
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Ingår i: Scandinavian Journal of Immunology. - : John Wiley & Sons. - 0300-9475 .- 1365-3083. ; 86:4, s. 278-278
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Platelet activation and subsequent thrombus formation is a well‐defined process to maintain vascular integrity upon tissue damage. However, platelets are also activated by an array of inflammatory stimuli, including microbial infection. Further, circulating platelets contain intracellular IgG that are released upon activation.Aim: We aimed to elucidate the physiologic function of platelet‐derived IgGs and their effect on viral infections.Methods: IgG levels, subclass and light chain distributions were quantified by ELISA. For neutralization assays, CMV‐infected HUVECs were perfused with platelets or plasma of anti‐CMV IgG seropositive or seronegative donors before quantification of infection by IF or qPCR. IgG content of neonatal Fc‐receptor (FcRn)‐deficient or wild‐type murine megakaryocytes (MK) was measured by flow cytometry.Results: Human platelets can store and release anti‐IAV and anti‐CMV IgG. Platelets from anti‐CMV IgG seropositive but not seronegative donors potently neutralized in vitro CMV‐infection under microvascular shear stress. In spite of containing approximately 100‐fold less IgG, platelets were equally efficient at neutralization as plasma from the same donor. Platelets were not enriched for a specific IgG subclass, nor for a specific kappa or lambda light chain. As MKs contain FcRn, sequestration of IgG might occur in the shared microenvironment of MKs and plasma cells. Indeed, MK FcRn was partially responsible for IgG uptake and may thus rescue IgG from degradation after endocytosis.Conclusion: Our data show that platelets have the potential to mediate potent IgG‐mediated antiviral effects directly at foci of infection, indicating that platelet activation may represent a novel mechanism for focused serological immunity.
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| 4. |
- Waltraud, Schrottmaier, et al.
(författare)
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Direct and indirect effects of Puumala hantavirus on platelet function
- 2024
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Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 233, s. 41-54
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Tidskriftsartikel (refereegranskat)abstract
- Thrombocytopenia is a cardinal symptom of hantavirus-induced diseases including Puumala virus (PUUV)-induced hemorrhagic fever with renal syndrome (HFRS), which is associated with impaired platelet function, bleeding manifestations and augmented thrombotic risk. However, the underlying mechanisms causing thrombocytopenia and platelet hypo-responsiveness are unknown. Thus, we investigated the direct and indirect impact of PUUV on platelet production, function and degradation. Analysis of PUUV-HFRS patient blood revealed that platelet hypo-responsiveness in PUUV infection was cell-intrinsic and accompanied by reduced platelet-leukocyte aggregates (PLAs) and upregulation of monocyte tissue factor (TF), whereas platelet vasodilator-stimulated phosphoprotein (VASP) phosphorylation was comparable to healthy controls. Plasma CXCL4 levels followed platelet count dynamics throughout disease course. PUUV activated both neutrophils and monocytes in vitro, but platelet desialylation, degranulation and GPIIb/IIIa activation as well as PLA formation and endothelial adhesion under flow remained unaltered in the presence of PUUV. Further, MEG-01 megakaryocytes infected with PUUV displayed unaltered polyploidization, expression of surface receptors and platelet production. However, infection of endothelial cells with PUUV significantly increased platelet sequestration. Our data thus demonstrate that although platelet production, activation or degradation are not directly modulated, PUUV indirectly fosters thrombocytopenia by sequestration of platelets to infected endothelium. Upregulation of immunothrombotic processes in PUUV-HFRS may further contribute to platelet dysfunction and consumption. Given the pathophysiologic similarities of hantavirus infections, our findings thus provide important insights into the mechanisms underlying thrombocytopenia and highlight immune-mediated coagulopathy as potential therapeutic target.
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