A5060480065- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Monoclonal and Polyclonal Antibodies Research
- T-cell and B-cell Immunology
- Systemic Lupus Erythematosus Research
- Renal Transplantation Outcomes and Treatments
- Platelet Disorders and Treatments
- Blood groups and transfusion
- Immune Cell Function and Interaction
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Vasculitis and related conditions
- Immunotherapy and Immune Responses
- Cell Adhesion Molecules Research
- Blood Coagulation and Thrombosis Mechanisms
- Organ Transplantation Techniques and Outcomes
- Glycosylation and Glycoproteins Research
- Immune Response and Inflammation
- Xenotransplantation and immune response
- Phagocytosis and Immune Regulation
- Erythrocyte Function and Pathophysiology
- Hemoglobinopathies and Related Disorders
- Reproductive System and Pregnancy
- Galectins and Cancer Biology
- Retinal Diseases and Treatments
- Autoimmune Bullous Skin Diseases
Leiden University Medical Center
2013-2023
University Medical Center Groningen
2013-2023
University of Groningen
1996-2023
Leiden University
2011-2022
Dialyse Centrum Groningen
2022
RELX Group (United States)
2018
May Institute
2011
Evidence Based Research (United States)
2008
Therapeutic Guidelines
2008
Sanquin
2002-2008
In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of 2015 Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues management these 2 diseases were considered by global panel experts. Areas addressed included renal pathology, clinical phenotype assessment, genetic drivers disease, acquired treatment strategies. order to help guide clinicians who...
Abstract Objective . To define variations in the cellular infiltrate and expression of monokines synovial tissue (ST) from rheumatoid arthritis (RA) patients with different durations disease levels activity. Methods The immunohistologic features biopsy specimens 31 early RA (<1 year) 35 longstanding (>5 years) were compared. possible associations between these local activity, as measured by score for pain biopsied knee joint, also evaluated. Results not dependent on duration. We found...
Abstract The recently identified lectin pathway of the complement system, initiated by binding mannan-binding (MBL) to its ligands, is a key component innate immunity. MBL-deficient individuals show an increased susceptibility for infections, especially mucosal system. We examined whether IgA, important mediator immunity, activates system via pathway. Our results indicate dose-dependent MBL polymeric, but not monomeric IgA coated in microtiter plates. This interaction involves carbohydrate...
IgA nephropathy (IgAN) is characterized by glomerular co-deposition of and complement components. Earlier studies showed that activates the alternative pathway complement, whereas more recent data also indicate activation lectin pathway. The can be activated binding mannose-binding (MBL) ficolins to carbohydrate ligands, followed MBL-associated serine proteases C4. This study examined potential role in IgAN. Renal biopsies patients with IgAN (n=60) mesangial deposition IgA1 but not IgA2....
Abstract Objective . The effect of chimeric anti–tumor necrosis factor α (TNFα) monoclonal antibody (MAb) therapy on synovial inflammation was studied in order to address the hypothesis that anti‐TNFα leads down‐regulation adhesion molecules and a decrease inflammatory cell influx tissue (ST). Methods immunohistologic features biopsy specimens, both before 4 weeks after MAb (cA2) therapy, were 14 patients with rheumatoid arthritis (RA). either received placebo (n = 2), or given intravenous...
Introduction: The complement system is essential for an adequate immune response. Much attention has been given to the role of in disease. However, better understand pathology, it crucial first analyze this different physiological conditions. aim present study was therefore investigate inter-individual variation activity and influences age gender. Methods: Complement levels functional were determined 120 healthy volunteers, 60 women, men, range 20–69 year. Functional classical pathway (CP),...
Abstract Pentraxin 3 (PTX3) is a recently characterized member of the pentraxin family acute‐phase proteins produced during inflammation. Classical short pentraxins, C‐reactive protein, and serum amyloid P component can bind to C1q thereby activate classical complement pathway. Since PTX3 also C1q, present study was designed define interaction between examine functional consequences this interaction. A dose‐dependent binding both C1 complex observed. Experiments with recombinant globular...
Secretory IgA (SIgA) is a multi-polypeptide complex consisting of secretory component (SC) covalently attached to dimeric containing one joining (J) chain. We present the analysis both N- and O-glycans on individual peptides from this complex. Based these data, we have constructed molecular model SIgA1 with all its glycans, in which Fab arms form T shape SC wrapped around heavy chains. The O-glycan regions (H) chains N-glycans adhesin-binding glycan epitopes including galactose-linked β1-4...
The serum opsonin mannose-binding lectin (MBL) has been shown to be involved in the handling of apoptotic cells. However, at what stage process this happens and whether mediates activation complement is unknown. Cells rendered or necrotic were incubated with purified MBL/MBL-associated serine protease (MASP) complexes assessed by flow cytometry fluorescence microscopy. MBL bound specifically late cells, as well blebs but not early Binding could inhibited EDTA an antibody against CRD region....
Corticosteroids and the calcineurin inhibitors cyclosporin A (CsA) FK506 have been studied extensively regarding their effects on T lymphocytes, but dendritic cells (DC) are relatively unknown. Monocytes one of precursors DC that differentiate into CD14-CD1a+ immature upon culture with IL-4 GM-CSF. The presence CsA or during differentiation did not affect development. In contrast, corticosteroids, either dexamethasone (Dex) prednisolone (Pred), for as little first 48 h blocked generation DC....
Local production of cytokines plays a critical role in the regulation pathophysiologic processes leading to rejection transplanted organs. In present study, possible interleukin-17 (IL-17), recently identified cytokine with unique properties, was investigated. IL-17 is specifically produced by activated T cells, whereas biological activities are restricted activation nonhematopoietic cells. vitro, induced primary human proximal tubular epithelial type cell regulating local interstitial...
Abstract Objective It has been suggested that anti–citrullinated protein antibodies (ACPAs) play an important role in the pathogenesis of rheumatoid arthritis (RA). To exert their pathologic effects, ACPAs must recruit immune effector mechanisms such as activation complement system. Mouse models RA have shown that, surprisingly, arthritogenic activate alternative pathway rather than expected classical pathway. This study was undertaken to investigate whether human anti–cyclic citrullinated...
Abstract Deficiencies of early components the classical complement pathway, particularly C1q, are strongly associated with susceptibility to systemic lupus erythematosus. Recent data link this predisposal autoimmunity an inappropriate clearance apoptotic cells, which could lead a loss self-tolerance. In present study, we demonstrate that opsonization cells C1q and mannose-binding lectin allows facilitates their uptake not only by macrophages but also human immature dendritic (DCs). Both...
Abstract C3 nephritic factor (C3NeF) defined by the capacity of serum and its fractions to initiate loss B antigen in normal was purified from three different donors shown function stabilization membrane-bound fluid phase alternative pathway convertase. C3NeF converts cell-bound C3B̅ sites a dose-related manner C3B̅(NeF) sites, which exhibit approximate 10-fold increase half-life. The linear relationship between input residual hemolytic on EAC43B present after incubation for 20 min at 30°C,...
Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, SLE the presence anti-C1q is associated occurrence nephritis. We have generated mouse anti–mouse C1q mAb's and used murine models to investigate whether actually contribute renal pathology glomerular immune complex disease. Administration mAb JL-1, which recognizes collagen-like region C1q, resulted deposition mild granulocyte influx, but no...
Neutrophils play an important role in inflammatory processes the lung and may cause tissue injury through, for example, release of proteinases such as neutrophil elastase. In addition to elastase, stimulated neutrophils also small nonenzymatic cationic polypeptides termed defensins. The aim present study was investigate whether defensins induce interleukin (IL)-8 expression cells A549 epithelial cell line human primary bronchial (PBEC). Supernatants defensin-treated contained increased...
Anti-C1q autoantibodies are present in sera of patients with several autoimmune diseases, including systemic lupus erythematosus (SLE). Strikingly, SLE the presence anti-C1q is associated occurrence nephritis. We have generated mouse anti–mouse C1q mAb's and used murine models to investigate whether actually contribute renal pathology glomerular immune complex disease. Administration mAb JL-1, which recognizes collagen-like region C1q, resulted deposition mild granulocyte influx, but no...