Track topics on Twitter Track topics that are important to you
There have been many studies on mechanisms of internalization of DNA-anti-DNA immune complexes by cells, including the one used rheumatoid factor expressing mouse B cells. In parallel, studies on the role of intracellular DNA sensors in the pathogenesis of systemic lupus erythematosus (SLE) have been conducted including the one using a mouse model lacking one of the sensors. These and other data have established a framework for understanding the pathogenic role of anti-DNA antibodies, but studies on normal cells are limited. Here, we used the monoclonal anti-dsDNA antibody 2C10, 2 kbp dsDNA, and healthy human peripheral blood mononuclear cells (PBMCs) to test whether and how 2C10 and/or DNA cause pathology in normal cells. We found that on culture with PBMCs, 2C10 preferentially entered monocytes and that DNA enhanced this internalization. In contrast, DNA alone was not significantly internalized by monocytes, but 2C10 facilitated its internalization. This was suppressed by cytochalasin D, but not by methyl-β-cyclodextrin, chloroquine, or an Fc blocker, suggesting the involvement of macropinocytosis in this process. Internalization of 2C10 and DNA together resulted in production of IFN-α, IFN-γ, TNF-α, MCP-1, IL-1β, IL-6, IL-10 and IL-33 by PBMCs. Cytokine production was suppressed by chloroquine and shikonin, but not by RU.521, suggesting dependence on activation of the TLR9 and AIM2 pathways. These results established a simple model to demonstrate that anti-DNA antibodies can cause dysregulation of cytokine network mimicking SLE in culture of normal PBMCs, and emphasize again the importance of maintaining anti-DNA antibodies at low levels by treatment.
This article was published in the following journal.
Name: Clinical and experimental immunology
Anti-dsDNA antibody is a specific antibody in systemic lupus erythematosus (SLE). Indirect immunofluorescence test (IIFT) is a highly specific method in detecting anti-dsDNA antibody. The application ...
The antagonistic anti-CD40 antibody, 2C10, and its recombinant primate derivative, 2C10R4, are potent immunosuppressive antibodies whose utility in allo- and xenotransplantation have been demonstrated...
In this study, a carboxyl group was introduced into the isoprocarb molecule to obtain an isoprocarb hapten, which was then coupled with a protein to obtain an artificial antigen. Three monoclonal anti...
The study of cellular and molecular immunology is almost completely dependent on monoclonal antibody technology. Despite the relatively long history of monoclonal antibodies, there is still huge poten...
Secukinumab is a fully human monoclonal antibody that selectively neutralizes IL-17A, a key cytokine involved in psoriasis (PsO) and psoriatic arthritis (PsA) development, and has shown rapid and long...
This partially randomized phase I/II trial studies the side effects and the best dose of anti-endoglin monoclonal antibody TRC105 when given together with bevacizumab and to see how well t...
RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the ...
This phase I trial studies the safety and best dose of anti-LAG-3 (anti-LAG-3 monoclonal antibody BMS-986016) or urelumab alone and in combination with nivolumab in treating patients with ...
RATIONALE: Radiolabeled monoclonal antibodies, such as yttrium Y 90 DOTA anti-CEA monoclonal antibody M5A, can find tumor cells and carry tumor-killing substances to them without harming n...
The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of GC1008, a human anti-transforming growth factor-beta (TGFβ) monoclonal antibod...
An anti-VEGF recombinant monoclonal antibody consisting of humanized murine antibody. It inhibits VEGF receptors and prevents the proliferation of blood vessels.
An anti-CD52 ANTIGEN monoclonal antibody used for the treatment of certain types of CD52-positive lymphomas (e.g., CHRONIC LYMPHOCYTIC LEUKEMIA; CUTANEOUS T-CELL LYMPHOMA; and T-CELL LYMPHOMA). Its mode of actions include ANTIBODY-DEPENDENT CELL CYTOTOXICITY.
An anti-CTLA-4 ANTIGEN monoclonal antibody initially indicated for the treatment of certain types of metastatic MELANOMA. Its mode of actions may include blocking of CTLA-4 mediated inhibition of CYTOTOXIC T LYMPHOCYTES, allowing for more efficient destruction of target tumor cells.
An anti-IgE, recombinant, humanized monoclonal antibody which specifically binds to the C epsilon3 domain of IMMUNOGLOBULIN E, the site of high-affinity IgE receptor binding. It inhibits the binding of IgE to MAST CELLS and BASOPHILS to reduce the severity of the allergic response and is used in the management of persistent allergic ASTHMA.
Test for tissue antigen using either a direct method, by conjugation of antibody with fluorescent dye (FLUORESCENT ANTIBODY TECHNIQUE, DIRECT) or an indirect method, by formation of antigen-antibody complex which is then labeled with fluorescein-conjugated anti-immunoglobulin antibody (FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT). The tissue is then examined by fluorescence microscopy.
An antibody is a protein produced by the body's immune system when it detects harmful substances, called antigens. Examples of antigens include microorganisms (such as bacteria, fungi, parasites, and viruses) and chemicals. Antibodies may be produc...
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Biological therapy involves the use of living organisms, substances derived from living organisms, or laboratory-produced versions of such substances to treat disease. Some biological therapies for cancer use vaccines or bacteria to stimulate the body&rs...