A5052455528- Complement system in diseases
- Phagocytosis and Immune Regulation
- Platelet Disorders and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Systemic Lupus Erythematosus Research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Cell Adhesion Molecules Research
- Blood groups and transfusion
- Glioma Diagnosis and Treatment
- Renal Diseases and Glomerulopathies
- Nanoparticle-Based Drug Delivery
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune Response and Inflammation
- Protease and Inhibitor Mechanisms
- Immune Cell Function and Interaction
- Hemophilia Treatment and Research
- Immune cells in cancer
- Ferroptosis and cancer prognosis
- Monoclonal and Polyclonal Antibodies Research
- Vasculitis and related conditions
- Pain Management and Placebo Effect
- Adenosine and Purinergic Signaling
- Pediatric Pain Management Techniques
- Atherosclerosis and Cardiovascular Diseases
- Inflammasome and immune disorders
Lund University
2013-2025
Skåne University Hospital
2012-2022
Region Skåne
2019
Hôpitaux Universitaires de Strasbourg
2018
Wallenberg Wood Science Center
2010
Medizinische Hochschule Hannover
1998-2010
Abstract Ongoing inflammation including activation of the complement system is a hallmark systemic lupus erythematosus (SLE). Antimicrobial neutrophil extracellular traps (NETs) are composed secreted chromatin that may act as source autoantigens typical for SLE. In this study, we investigated how interacts with NETs and NET degradation affected by in SLE patients. We found sera from subset patients active had reduced ability to degrade vitro-generated NETs, which was mostly restored when...
After severe tissue injury, innate immunity mounts a robust systemic inflammatory response. However, little is known about the immediate impact of multiple trauma on early complement function in humans. In present study, we hypothesized that results activation, consumption, and dysfunction cascade resulting "complementopathy" may be associated with morbidity mortality. Therefore, prospective multicenter study 25 healthy volunteers 40 polytrauma patients (mean injury severity score = 30.3 ±...
The ability to degrade neutrophil extracellular traps (NETs) is reduced in a subset of patients with systemic lupus erythematosus (SLE). NETs consist chromatin covered antimicrobial enzymes and are normally degraded by DNase-I, an enzyme which known have activity SLE. Decreased associated disease activity. In the current study we investigated how serum from SLE varies during course as well what impact this may for clinical phenotype SLE.Serum 69 SLE, included prospective study, was taken...
C1q is the initiator of classical complement pathway and opsonizes apoptotic cells to facilitate phagocytosis. Deficiency strongest known risk factor for development systemic lupus erythematosus (SLE), which appears be related ensuing impaired clearance material. The objective current study was investigate new ligands on surface cells. We revealed that two phospholipid-binding proteins annexin A2 A5 are, beside DNA, significant ligands. furthermore, demonstrated binds directly histones...
Aberrant expression of miR-96 in prostate cancer has previously been reported. However, the role and mechanism action not determined. In this study, diagnostic prognostic properties levels were investigated by qRT-PCR two well documented cohorts. The was found to be significantly higher patients correlate with WHO grade, decreased overall survival time; low lived 1.5 years longer than high levels. therapeutic potential further vitro, showing that ectopic enhances growth cellular...
Apoptotic cells are opsonized by complement components such as C1q and C3b, which increases their susceptibility to phagocytosis. Soluble inhibitors factor H (fH) also recognize apoptotic minimize the pro-inflammatory effects of downstream activation. We used four radiolabeled protein constructs that span different regions 20 control (CCP) modules make up fH found fragments comprising CCPs 6–8, 8–15, 19–20 but not 1–4, bound Jurkat T cells. There possible ligand types on could recruit fH:...
Objective Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether copy is connected repertoire in lupus erythematosus (SLE), primary Sjögren's syndrome (SS), or myositis. Methods Using targeted DNA sequencing, we determined genetic variants 2,290 well‐characterized Scandinavian patients SLE, SS, myositis 1,251 healthy controls. Results A prominent relationship...
BackgroundInflammatory bowel disease (IBD) is a critical public health issue; more and people are affected, but treatment options remain limited. Complement activation the anaphylatoxin C5a have been shown to play role in IBD. In this study, mouse models of acute chronic dextran sulfate-induced colitis were used further elucidate impact its receptor (C5aR) on development.
In the present study, we sought to evaluate complement activation product C4d as a marker for lupus nephritis in systemic erythematosus (SLE).C4d levels were determined by enzyme-linked immunosorbent assay plasma samples of patients with established SLE using novel approach based on detection short linear cleavage neoepitope. Cross-sectional associations studied 98 taken at lower or higher respective disease activity. Temporal investigated 69 who followed longitudinally up 5 years. Plasma...
<p>FH is expressed in human glioma and correlates with disease severity. FH produced lower-grade (<b>A</b>) GBM (<b>B</b>). <b>C,</b> expression decreased overall survival (<b>C</b>) disease-free (<b>D</b>) of patients glioma. Expression primary therapy outcome (<b>E</b>), cancer type (<b>F</b>), neoplasm histological grade (<b>G</b>), new event post-initial (<b>H</b>),...
<p>Supplementary figure 2. FH in Ntv-a mouse model (A) Mouse binds to derived primary Tregs. Tregs were incubated for 2 h at 4oC with fluorescently labeled 25 or 100 μg/mL FH. The binding was detected using flow cytometry. (B) Western blot detecting supernatants of tumor cells isolated from mice. partially depleted antibody against bound Dynabeads. (C) FH-rendered increase survival cell supernatant and FH-depleted supernatant. After 7 days viability assessed by Annexin V Via-Probe...
<p>FH increases the viability of Tregs. FH-rendered increase in survival CD4<sup>+</sup> (<b>A</b>) but not CD8<sup>+</sup> (<b>B</b>) or naïve (<b>C</b>) T cells. FH increased Tregs (<b>D</b>) and did Treg-depleted cells (<b>E</b>). Cells were incubated with medium, 150 μg/mL FH, α1-AT for 7 days, assessed by Annexin V Via-Probe staining. <b>F,</b> Gating according to ICOS expression....
<p>FH binds to T cells via ICOS. <b>A,</b> Biotinylated FH CD4<sup>+</sup> upon incubation for 2 hours with TexMACS medium alone and supplemented 50 100 μg/mL FH. <b>B,</b> Fractionation detecting binding but not internalization into cells, incubated 150 at 4°C or 37°C. <b>C,</b> HuProt microarray showing top-specific proteins CCP19-20. <b>D</b> <b>E,</b> PLA activated were 37°C, the interaction between ICOS was...
<div>Abstract<p>The survival rate of patients with glioma has not significantly increased in recent years despite aggressive treatment and advances immunotherapy. The limited response to treatments is partially attributed the immunosuppressive tumor microenvironment, which regulatory T cells (Treg) play a pivotal role immunologic tolerance. In this study, we investigated impact complement factor H (FH) on Tregs within microenvironment found that FH an ICOS ligand. binding immune...
<p>Supplementary figure 3. Direct effect of FH on glioma cells Proliferation PIGPC treated with medium only, 25- or 100-μg/mL (A) and H4 mock FH-transfected (B) was analyzed after 24, 48, 72 96 hours using CyQUANT assay. Data obtained at 24 used for the normalization. (C) Correlation between Ki67 gene expression in tumor from patients, GEO database. Survival pretreated 100 μg/mL (D-F) (G-I) rendered apoptotic by treatment 0.75 uM staurosporine h. Viability assessed Annexin V Via-Probe...
<p>Supplementary figure 4. Staining control for human samples and additional information about patients (A) Histology (B) clinical parameters of glioma patients. MGMT-methylation status; TMZ-temozolomide; Adj-adjusted. WT – wild type.</p>
<p>FH knockdown is associated with a lower number of ICOS<sup>+</sup> Tregs in murine glioma model. FH expression was investigated gliomas generated using the RCAS/tv-a vectors to induce <i>PDGFB</i> (<b>A</b> and <b>B</b>) <i>shp53</i> (<b>B</b>). <b>C,</b> Schematic illustration mouse Increased survival (<b>D</b>), decrease Olig2<sup>+</sup> tumor cells (<b>E</b>),...
<p>ICOS is associated with poor prognosis of patients glioma. <b>A,</b> ICOS expression correlates decreased survival Expression neoplasm histological grade (<b>B</b>), cancer type (<b>C</b>), and <i>EGFR</i> mutations (<b>D</b>). positively infiltration Tregs (<b>E</b>) negatively CD8<sup>+</sup> T cells (<b>F</b>) CD4<sup>+</sup> (<b>G</b>) in lower-grade...
<p>FH enhances the immunosuppressive function of Tregs. <b>A,</b> FH increases effect Tregs were incubated in medium only or supplemented with 150 μg/mL FH. CD4<sup>+</sup> T cells isolated from same donor and cocultured presence CD2/CD3/CD28 MACSiBeads <sup>3</sup>H-thymidine. Secretion IL10 (<b>B</b> <b>D</b>) TGFβ (<b>C</b>) by only, α1-AT, FH, dFH. Cells stimulated anti-CD3 anti-CD28 microbeads IL2, secreted...
<p>Supplementary figure 6. FH expression in glioma correlates with pro-tumorigenic markers</p>
<p>FH in glioma correlates with Treg occurrence and increased viability. FH expression positively infiltration of Tregs lower-grade (<b>A</b>) GBM (<b>B</b>). <b>C,</b> Western blot detecting supernatants FH-transfected cell lines depletion MRC-OX24-bound Dynabeads. <b>D,</b> incubated H4 line exhibited survival, the effect is weaker when partially depleted. Correlation analysis immune was performed using TIMER2.0, based on...
<p>Supplementary figure 5. FH, ICOSL and ICOS dependence on glioma patient survival. The survival data of <i>n</i> = 509 patients from TCGA provisional dataset brain lower-grade glioma, analyzed with cBioPortal. Statistical tests: Logrank Test.</p>