| 1. |
- Håkansson, Irene, 1976-, et al.
(författare)
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Complement activation in cerebrospinal fluid in clinically isolated syndrome and early stages of relapsing remitting multiple sclerosis
- 2020
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Ingår i: Journal of Neuroimmunology. - : Elsevier. - 0165-5728 .- 1872-8421. ; 340
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Tidskriftsartikel (refereegranskat)abstract
- To assess if markers of complement activation are associated with disease activity, C1q, C3, C3a and sC5b-9 levels in plasma and cerebrospinal fluid (CSF) were determined in 41 patients with clinically isolated syndrome (CIS) or remitting multiple sclerosis (RRMS), in a prospective longitudinal four-year cohort study. C1q in CSF (CSF-C1q) was significantly higher in patients than in controls. Baseline CSF-C1q and CSF-C3a correlated with several neuroinflammatory markers and neurofilament light chain levels. Baseline CSF-C3a correlated with the number of T2 lesions at baseline and new T2 lesions during follow-up. Baseline CSF-C3a was also significantly higher in patients with (n = 21) than in patients without (n = 20) signs of disease activity according to the NEDA-3 concept during one year of follow-up (p ≤ .01) Study results support that complement activation is involved in MS pathophysiology and that CSF-C3a carries prognostic information.
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| 2. |
- Högberg, Cecilia, et al.
(författare)
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Qualitative faecal immunochemical tests (FITs) for diagnosing colorectal cancer in patients with histories of rectal bleeding in primary care : a cohort study
- 2020
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Ingår i: International Journal of Colorectal Disease. - : Springer. - 0179-1958 .- 1432-1262. ; 35, s. 2035-2040
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Tidskriftsartikel (refereegranskat)abstract
- Background Rectal bleeding is considered an alarm symptom for colorectal cancer (CRC) but it is common and mostly caused by benign conditions. Qualitative faecal immunochemical tests (FITs) for occult blood have been used as diagnostic aids for many years in Sweden when CRC is suspected. The study aimed to evaluate the usefulness of FITs requested by primary care physicians for patients with and without histories of rectal bleeding, in the diagnosis of CRC. Methods Results of all FITs requested in primary care for symptomatic patients in the orebro region during 2015 were retrieved. Data on each patient's history of rectal bleeding was gathered from electronic health records. Patients diagnosed with CRC within 2 years were identified from the Swedish Cancer Register. The analysis focused on three-sample FITs, the customary FIT in Sweden. Results A total of 4232 patients provided three-sample FITs. Information about the presence/absence of rectal bleeding was available for 2027 patients, of which 59 were diagnosed with CRC. For 606 patients with the presence of rectal bleeding, the FIT showed sensitivity 96.2%, specificity 60.2%, positive predictive value 9.8% (95% CI 6.1-13.4) and negative predictive value 99.7% (95% CI 99.2-100) for CRC. For 1421 patients without rectal bleeding, the corresponding figures were 100%, 73.6%, 8.3% (95% CI 5.6-10.9) and 100% (95% CI 99.6-100). Conclusion The diagnostic performance of a qualitative three-sample FIT provided by symptomatic patients in primary care was similar for those with and without a history of rectal bleeding. FITs seem useful for prioritising patients also with rectal bleeding for further investigation.
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| 3. |
- Ekelund, Oskar, et al.
(författare)
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High-throughput immunoassays for SARS-CoV-2 : considerable differences in performance when comparing three methods
- 2021
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Ingår i: Infectious Diseases. - : Taylor & Francis. - 2374-4235 .- 2374-4243. ; 53:10, s. 805-810
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The recently launched high-throughput assays for detecting antibodies against SARS-CoV-2 has contributed to the managing strategies for the COVID-19 pandemic. This study aimed to investigate the performance of three high-throughput assays and one rapid lateral flow test relative to regulatory authorities' recommended criteria.METHODS: A total of 315 samples, including 150 pre-pandemic samples, 152 samples from SARS-CoV-2 RT-PCR positive individuals and 13 potentially cross-reactive samples were analysed with SARS-CoV-2 IgG (Abbott, Abbott Park, IL), Elecsys Anti-SARS-CoV-2 (Roche, Solna, Sweden), LIAISON SARS-CoV-2 S1/S2 IgG (DiaSorin, Saluggia, Italy) and 2019-nCOV IgG/IgM Rapid Test (Dynamiker Biotechnology Co., Tianjin, China).RESULTS: All assays performed with a high level of specificity ranging from 96.7% to 99.3%. Sensitivity differed more between the assays, Roche exhibiting the highest sensitivity of 98.7%. The corresponding figures for Abbott, DiaSorin and Dynamiker Biotechnology were 80.9%, 89.0% and 72.4%, respectively.CONCLUSIONS: The results of the evaluated SARS-CoV-2 assays vary considerably, as well as their ability to fulfil the performance criteria proposed by regulatory authorities. Introduction into clinical use in low-prevalent settings, should, therefore, be made with caution.
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| 4. |
- Norda, Rut, et al.
(författare)
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Complement activation products in liquid stored plasma and C3a kinetics after transfusion of autologous plasma
- 2012
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Ingår i: Vox Sanguinis. - Malden : Wiley-Blackwell. - 0042-9007 .- 1423-0410. ; 102:2, s. 125-133
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: Keeping a small stock of liquid plasma readily available for transfusion is common practise in Sweden. We report data on complement activation markers in plasma components during storage in the liquid state and the kinetics of C3a-desArg after transfusion of autologous plasma with high content of C3a-desArg.Material and Methods: Plasma components were prepared by apheresis or from whole blood. C3 fragments (C3a-desArg, C3d, g, iC3), and soluble terminal complement complex (sC5b-9) were investigated. C3a-desArg kinetics was investigated in regular apheresis donors.Results: Apheresis plasma prepared by membrane centrifugation had significantly higher level of C3a-desArg, C3d, g and sC5b-9 from day 0 and low iC3, than plasma prepared by other methods. By storage day 7, C3a-desArg -levels were above the reference value in 88% of all components. After re-infusion of autologous plasma with high C3a-desArg content, there were rapid a1 and a2-distribution followed by a slower b-elimination phase.Conclusion: Plasma components prepared by different methods and stored in the liquid phase differ significantly in the amount and timing of complement activation. C3a-desArg present in plasma is rapidly eliminated after transfusion. Autologous plasma could be used to study complement kinetics in different clinical situations.
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| 5. |
- Somajo, Sofia, et al.
(författare)
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Protein S and factor V in regulation of coagulation on platelet microparticles by activated protein C
- 2014
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Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 134:1, s. 144-152
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Platelets are the main source of microparticles in plasma and the concentration of microparticles is increased in many diseases. As microparticles expose negatively charged phospholipids, they can bind and assemble the procoagulant enzyme-cofactor complexes. Our aim was to elucidate possible regulation of these complexes on microparticles by the anticoagulant protein C system.Materials and methods: Platelets were activated with thrombin ± collagen or the calcium ionophore A23187 ± thrombin to generate microparticles. The microparticles were analyzed using flow cytometry and functional coagulation assays to characterize parameters with importance for the activated protein C system.Results: Activation with A23187 + thrombin was most efficient, fully converting the platelets to microparticle-like vesicles, characterized by high lactadherin and protein S binding capacity. Suppression of thrombin generation by activated protein C in plasma spiked with these microparticles was dependent on the presence of plasma protein S. Experiments with purified components showed that activated protein C inhibited both factor Va and factor VIIIa on the microparticle surface. Inhibition of factor Va was stimulated by, but not fully dependent on, the presence of protein S. In the factor VIIIa-degradation, activated protein C was dependent on the addition of protein S, and exogenous factor V further increased the efficiency.Conclusions: Protein S is crucial for activated protein C-mediated inhibition of thrombin generation on platelet-derived microparticles in plasma. Moreover, protein S and factor V are synergistic cofactors in the inhibition of factor VIIIa. The results demonstrate that the activated protein C system has the capacity to counterbalance the procoagulant ability of microparticles.
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| 6. |
- Asif, Sana, M.D, PhD student, et al.
(författare)
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Validation of an MPC polymer coating to attenuate surface- induced cross-talk between the complement and coagulation systems in whole blood in in vitro and in vivo models
- 2019
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Ingår i: Macromolecular Bioscience. - : Wiley-VCH Verlagsgesellschaft. - 1616-5187 .- 1616-5195. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Artificial surfaces that come into contact with blood induce an immediate activation of the cascade systems of the blood, leading to a thrombotic and/or inflammatory response that can eventually cause damage to the biomaterial or the patient, or to both. Heparin coating has been used to improve hemocompatibility, and another approach is 2-methacryloyloxyethyl phosphorylcholine (MPC)-based polymer coatings. Here, the aim is to evaluate the hemocompatibility of MPC polymer coating by studying the interactions with coagulation and complement systems using human blood in vitro model and pig in vivo model. The stability of the coatings is investigated in vitro and MPC polymer-coated catheters are tested in vivo by insertion into the external jugular vein of pigs to monitor the catheters' antithrombotic properties. There is no significant activation of platelets or of the coagulation and complement systems in the MPC polymer-coated one, which was superior in hemocompatibility to non-coated matrix surfaces. The protective effect of the MPC polymer coat does not decline after incubation in human plasma for up to 2 weeks. With MPC polymer-coated catheters, it is possible to easily draw blood from pig for 4 days in contrast to the case for non-coated catheters, in which substantial clotting is seen.
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| 7. |
- Carlsson, Martin, et al.
(författare)
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Erythrocyte fatty acid composition does not influence levels of free, bioavailable, and total 25-hydroxy vitamin D
- 2017
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 77:1, s. 45-52
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Tidskriftsartikel (refereegranskat)abstract
- In vitro, mono- and polyunsaturated fatty acids (FAs) may decrease the binding affinity of vitamin D metabolites for vitamin D-binding protein, which in turn may influence their bioavailability. FAs incorporated as phospholipids in erythrocyte (ery-) cell membranes reflect dietary intake. The purpose of this study was to investigate ery-FA composition in relation to markers for vitamin D. In healthy females (age 22.6 +/- 2.0 years) total 25(OH)D was measured by LC-MS/MS (n=78), free 25(OH)D with ELISA (n=64 of 78), and bioavailable 25(OH)D was calculated. Analysis of ery-FA composition was by gas chromatography (n=56 of 78). A strong correlation between total 25(OH)D and free 25(OH)D was seen (r=.66, p<.001), and between total-25(OH)D and bioavailable 25(OH)D (r=.68, p<.001). No correlations between 25(OH)D fractions and specific fatty acids were found, and in particular, no associations with mono- and poly-unsaturated FA compositions. All 25(OH)D fractions were correlated with leptin (total 25(OH)D (r=-.33, p<.003); bioavailable 25(OH)D (r=-.47, p<.001); free 25(OH)D (r=-.44, p<.001). Associations were found between PTH and total 25(OH)D (r=-.35, p=.002) and weaker between bioavailable 25(OH)D (r=-.35, p=.040) and free 25(OH)D (r=-.28, p=.079). All fractions of 25(OH)D appear to correlate in a similar way to PTH, BMI and body fat (leptin). No association was found between ery-FA composition and free/bioavailable 25(OH)D. It is unlikely that FAs are a strong uncoupling factor of DBP-bound 25(OH)D.
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| 8. |
- Carlsson, Sofia, et al.
(författare)
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Dependence on Vitamin K-dependent Protein S for Eukaryotic Cell Secretion of the β-Chain of C4b-binding Protein
- 2010
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Ingår i: Journal of Biological Chemistry. - : The American Society for Biochemistry and Molecular Biology. - 0021-9258 .- 1083-351X. ; 285:42, s. 32038-32046
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Tidskriftsartikel (refereegranskat)abstract
- The anticoagulant vitamin K-dependent protein S (PS) circulates in plasma in two forms, 30% free and 70% being bound to the complement regulatory protein C4b-binding protein (C4BP). The major C4BP isoform consists of 7 α-chains and 1 β-chain (C4BPβ+), the chains being linked by disulfide bridges. PS binds to the β-chain with high affinity. In plasma, PS is in molar excess over C4BPβ+ and due to the high affinity, all C4BPβ+ molecules contain a bound PS. Taken together with the observation that PS-deficient patients have decreased levels of C4BPβ+, this raises the question of whether PS is important for secretion of the β-chain from the cell. To test this hypothesis, HEK293 cells were stably and transiently transfected with β-chain cDNA in combinations with cDNAs for PS and/or the α-chain. The concentration of β-chains in the medium increased after co-transfection with PS cDNA, but not by α-chain cDNA, suggesting secretion of the β-chains from the cells to be dependent on concomitant synthesis of PS, but not of the α-chains. Thus, β-chains that were not disulfide-linked to the α-chains were secreted in complex with PS, either as monomers or dimers. Pulse-chase demonstrated that the complexes between PS and β-chain were formed intracellularly, in the endoplasmic reticulum. In conclusion, our results demonstrate that successful secretion of β-chains depends on intracellular complex formation with PS, but not on the α-chains. This provides an explanation for the decreased β-chain levels observed in PS-deficient patients.
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| 9. |
- Livaja Koshiar, Ruzica, et al.
(författare)
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Erythrocyte-derived microparticles supporting activated protein C-mediated regulation of blood coagulation.
- 2014
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 9:8
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Tidskriftsartikel (refereegranskat)abstract
- Elevated levels of erythrocyte-derived microparticles are present in the circulation in medical conditions affecting the red blood cells. Erythrocyte-derived microparticles expose phosphatidylserine thus providing a suitable surface for procoagulant reactions leading to thrombin formation via the tenase and prothrombinase complexes. Patients with elevated levels of circulating erythrocyte-derived microparticles have increased thrombin generation in vivo. The aim of the present study was to investigate whether erythrocyte-derived microparticles are able to support the anticoagulant reactions of the protein C system. Erythrocyte-derived microparticles were isolated using ultracentrifugation after incubation of freshly prepared erythrocytes with the ionophore A23187 or from outdated erythrocyte concentrates, the different microparticles preparations yielding similar results. According to flow cytometry analysis, the microparticles exposed phoshatidylserine and bound lactadherin, annexin V, and protein S, which is a cofactor to activated protein C. The microparticles were able to assemble the tenase and prothrombinase complexes and to stimulate the formation of thrombin in plasma-based thrombin generation assay both in presence and absence of added tissue factor. The addition of activated protein C in the thrombin generation assay inhibited thrombin generation in a dose-dependent fashion. The anticoagulant effect of activated protein C in the thrombin generation assay was inhibited by a monoclonal antibody that prevents binding of protein S to microparticles and also attenuated by anti-TFPI antibodies. In the presence of erythrocyte-derived microparticles, activated protein C inhibited tenase and prothrombinase by degrading the cofactors FVIIIa and FVa, respectively. Protein S stimulated the Arg306-cleavage in FVa, whereas efficient inhibition of FVIIIa depended on the synergistic cofactor activity of protein S and FV. In summary, the erythrocyte-derived microparticle surface is suitable for the anticoagulant reactions of the protein C system, which may be important to balance the initiation and propagation of coagulation in vivo.
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