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Sökning: WFRF:(Taxiarchis A)

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1.
  • Juto, A, et al. (författare)
  • MYELOPEROXIDASE (MPO) POSITIVE EXTRACELLULAR VESICLES (EVS) EXPRESSING COMPLEMENT SPLIT PRODUCTS IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS (AAV)
  • 2022
  • Ingår i: ANNALS OF THE RHEUMATIC DISEASES. - : BMJ. - 0003-4967 .- 1468-2060. ; 81, s. 1434-1434
  • Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
    • Complement activation has a critical role for the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We have previously shown increased expression of complement split products C3a and C5a on myeloperoxidase (MPO) positive EVs (MPO+EVs) in plasma from AAV patients with kidney involvement compared to the patients with non-renal disease and the EV-levels correlated with disease activity (1).ObjectivesTo investigate the expression of a larger set of complement components on circulating MPO+EVs in relation to disease activity and kidney involvement in patients with AAV.MethodsEighty-nine patients with AAV and 23 healthy controls were included. The concentration of MPO+EVs expressing complement split products C3a, C4d, C5a, terminal complement complex-TCC (C5b-9) or complement factor B (CFB) were analyzed from citrate plasma by flow cytometry. The assessment of vasculitis disease activity was performed using the Birmingham Vasculitis Activity Score (BVAS).ResultsIn the AAV group, there were 47 males (52.8%), the median age was 56 years and 33 (37.1%) patients were anti-MPO-positive and 54 (60.7%) were anti-PR3-positive. Two patients were positive for both antibodies. Median disease duration for patients with active AAV (BVAS>0; n=81) was 4 days and for patients in remission (BVAS 0; n=8) 1259 days. 64% had kidney involvement (n=52). Highly active AAV (BVAS ≥12) was noted in 62 patients, of whom 49 patients had kidney involvement. Active disease (0<BVAS<12) was seen in 19 patients. AAV patients had significantly higher levels of MPO+, MPO+C3a+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p<0.001). Patients in remission had higher levels of MPO+, MPO+C4d+ and MPO+TCC+ EVs compared to healthy controls (all p≤0.001). There was a significant difference in levels of MPO+(p=0.02), MPO+C3a+(p<0.001), MPO+C4d+(p<0.001) and MPO+TCC+ EVs (p<0.001) in patients with kidney involvement compared with patients without (n=29) (Figure 1). For patients with BVAS>0 there was a weak correlation between MPO+, MPO+C3a+, MPO+C4d+, MPO+TCC+ EVs and BVAS. Kidney biopsies from 34 patients were classified according to histopathological class (2): crescentic (n=6), focal (n=18), mixed (n=6), sclerotic (n=4). The level of MPO+C4d+EVs was higher in the sclerotic type compared to focal (p=0.04, 95% CI [2.4–103.7]) and mixed (p=0.04, 95% CI [1.4–119.1]).ConclusionLevels of EVs expressing complement split products were generally increased in AAV patients and patients with kidney involvement had higher levels of total MPO+EVs exposing C3a, C4d or TCC compared with patients without suggesting a role in kidney AAV pathogenesis. Patients with sclerotic kidney histotype had higher levels of MPO+C4d EVs compared with focal and mixed subgroups pointing to that activation of the classical complement pathway may be of importance in severe forms of kidney AAV.References[1]Antovic A et al. J Rheumatol. 2020 May 1;47(5):714-721. doi: 10.3899/jrheum.181347. Epub 2019 Aug 1. PMID: 31371653.[2]Berden AE et al. J Am Soc Nephrol. 2010 Oct;21(10):1628-36. doi: 10.1681/ASN.2010050477. Epub 2010 Jul 8. PMID: 20616173.Disclosure of InterestsNone declared
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  • Zong, Y., et al. (författare)
  • Phosphatidylserine positive microparticles improve hemostasis in in-vitro hemophilia A plasma models
  • 2020
  • Ingår i: Scientific Reports. - : Nature Research. - 2045-2322. ; 10:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating microparticles (MPs) are procoagulant due to the surface containing phosphatidylserine (PS), which facilitates coagulation. We investigated if MPs improve hemostasis in HA plasma models. MPs isolated from pooled normal human plasma were added to severe, moderate and mild HA plasma models (0%, 2.5%, 20% FVIII). The MPs’ effect on hemostasis was evaluated by calibrated automated thrombogram (CAT) and overall hemostasis potential (OHP) assays, while fibrin structure was imaged by standard confocal, stimulated emission depletion (STED) microscopy and scanning electron microscopy (SEM). MPs partially restored thrombin generation and fibrin formation in all HA plasma models. The procoagulant effect of MPs requires PS exposure, to a less extent of contact pathway activation, but not tissue factor exposure or in vitro stimulation of MPs. MPs partially normalized the fibrin structure, and using super-resolution STED, MPs attached to fibrin were clearly resolved. In summary, our results demonstrate that PS positive MPs could improve hemostasis in HA plasma models.
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