Search results for "CD40"
showing 10 items of 122 documents
Interleukin-12 release by mitogen-stimulated mononuclear cells in the elderly.
1998
Abstract Defects involving cellular expression of activation molecules, cell mediated immune response and natural killer (NK) activity are commonly observed in the elderly. Herein, data are reported on the evaluation of IL-12 production by old subjects. IL-12 is, actually, considered the key molecule for the induction of a T helper 1 (Th1) -type and NK response. IL-12 production from old subjects peripheral blood mononuclear cells (PBMNC) was evaluated using T-independent (bacterial lipopolysaccharide, LPS) or -dependent (phytoemagglutinin, PHA; immobilized anti-CD3 monoclonal antibodies, anti-CD3) mitogens. The IL-12 production after LPS stimulation was not reduced in cultures from old sub…
Both IL-12p70 and IL-23 are synthesized during active Crohnʼs disease and are down-regulated by treatment with anti-IL-12 p40 monoclonal antibody
2005
Background: Interleukin (IL)-12p70 and IL-23 are key T helper-1 (TH1) cytokines that drive the inflammation seen in numerous models of intestinal inflammation. These molecules contain an identical p40 chain that is bound to a p35 chain in IL-12 and a p19 chain in IL-23, making both potentially susceptible to modulation by an anti-IL-12p40 monoclonal antibody (mAb). Methods: In the present study, we sought to determine whether active inflammation in Crohn's disease (CD) is associated with the increased synthesis of both of these cytokines and whether patients treated with an anti-IL-12p40 mAb down-regulate IL-23 as well as IL-12p70 as previous reported. Results: To this end we initially dete…
Precision Medicine in Graves’ Disease: CD40 Gene Variants Predict Clinical Response to an Anti-CD40 Monoclonal Antibody
2021
BackgroundCD40, a key co-stimulatory molecule expressed on antigen-presenting cells, is genetically associated with a number of autoimmune diseases including Graves’ disease (GD). Therefore, recent therapies targeting CD40 have been developed, including the anti-CD40 monoclonal antibody Iscalimab. In a recent pilot study, Iscalimab was shown to induce clinical remission in ~ 50% of GD patients, but the reason why only 50% of GD patients responded is not known. The aim of our study was to test the hypothesis that specific CD40 single nucleotide polymorphism (SNP) genotypes and haplotypes are associated with clinical response of GD patients to Iscalimab.MethodsWe extracted genomic DNA from th…
A Novel Anti-CD40 Monoclonal Antibody, Iscalimab, for Control of Graves Hyperthyroidism—A Proof-of-Concept Trial
2019
Abstract Context The CD40-CD154 co-stimulatory pathway plays an important role in the pathogenesis of Graves disease (GD) by promoting autoreactive B-cell activation. Objective Evaluate efficacy and safety of a human, blocking, nondepleting anti-CD40 monoclonal antibody, iscalimab, in hyperthyroid patients with GD. Design Open-label, phase II proof-of-concept study. Setting Multicenter. Patients Fifteen with GD. Intervention Patients received 5 doses of iscalimab at 10 mg/kg intravenously over 12 weeks. Main outcome measures Thyroid-related hormones and autoantibodies, plasma soluble CD40, free CD40 on B cells, soluble CXCL13, pharmacokinetics, and safety were assessed. Results The iscalima…
C-reactive protein but not soluble CD40 ligand and homocysteine is associated to common atherosclerotic risk factors in a cohort of coronary artery d…
2009
Abstract Objectives One third to one half of the variation in vascular disease occurrence remains unexplained by traditional risk factors. Since atherosclerosis may, in part, be an inflammatory disease, circulating factors related to inflammation may be predictors of cardiovascular disease. The aim of this study was to evaluate the association between common atherosclerotic risk factors and markers of inflammation. Design and methods Serum levels of soluble CD40 (sCD40L), high-sensitive C-reactive protein (hs-CRP) and homocysteine (Hcy) were measured in 251 patients selected from a series of 438 subjects affected by previous myocardial infarction, angina or other cardiovascular diseases. Re…
Clinical and immunohistochemical evaluation of the vulvar Langerhans cell histiocytosis.
2008
: We present the case of a woman with diabetes insipidus with subsequent genital and multiorgan Langerhans cell histiocytosis (LCH). A monolateral and slightly infiltrated erythematous plaque of the vulva was observed. Hematoxylin and eosin and immunophenotypic studies were performed. The primary antibodies used were monoclonal antibody to S100, CD1a, CD34, HLA-DR, PCNA, CD45Ro, CD40, and langerin. The histology of the infiltrates revealed a granulomatous reaction pattern, with extensive aggregates of histiocyte proliferation. The histiocytes, morphologically characterized by a pale staining of cytoplasm surrounding a grooved reniform nucleus, sometimes contained small distinct nucleoli. L…
Double Negative (CD19+IgG+IgD-CD27-) B Lymphocytes: A New Insight from Telomerase in Healthy Elderly, in Centenarian Offspring, and in Alzheimer’s Di…
2014
Background: We have previously reported the increase of IgD-CD27- (Double Negative, DN) B cell population in the aged. These memory B cells have short telomeres and poor abilities to proliferate in vitro. Here, we investigated whether the low ability of DN B cells to proliferate depends on the expression levels of the CD307d and CD22 inhibitory receptors or whether DN B cells can proliferate and reactivate telomerase by the engagement of both innate and adaptive immune receptors. Methods: Phenotypic analyses were made by using flow cytometry. Quantitative analysis of telomerase activity was made by using a TRAP and a photometric enzyme immunoassay in young, healthy elderly, centenarian offs…
B cells in the aged: CD27, CD5, and CD40 expression.
2003
Ageing is characterized by numerous changes in lymphocyte subpopulations. In the present paper we have focused on B cells carrying the surface markers CD27, CD5 and CD40. CD27 is considered a marker of primed (memory) cells and its engagement promotes the differentiation of memory B cells into plasma cells. CD5 is expressed on B1 cells, which are considered to be responsible for T cell-independent antibody production other than autoantibodies. The CD40 molecule binds CD40L (CD154) and is necessary for T-dependent antibody responses. Here we show that the absolute number of CD5+ and CD40+ B cells is decreased in the elderly, while CD27+ B lymphocytes only marginally decrease in centenarians.…
IL-21 Regulates the Differentiation of a Human γδ T Cell Subset Equipped with B Cell Helper Activity
2012
Vγ9Vδ2 T lymphocytes recognize nonpeptidic antigens without presentation by MHC molecules and display pleiotropic features. Here we report that coculture of Vγ9Vδ2 cells with phosphoantigen and IL-21 leads to selective expression of the transcription repressor Bcl-6 and polarization toward a lymphocyte subset displaying features of follicular B-helper T (T(FH)) cells. T(FH) like Vγ9Vδ2 cells have a predominant central memory (CD27(+)CD45RA(-)) phenotype and express ICOS, CD40L and CXCR5. Upon antigen activation, they secrete IL-4, IL-10 and CXCL13, and provide B-cell help for antibody production in vitro. Our findings delineate a subset of human Vγ9Vδ2 lymphocytes, which, upon interaction w…
Pathological role of IL-6 in the experimental allergic bronchial asthma in mice.
2005
Although allergic asthma was described to be associated with the presence of mucosal T helper (Th)2 cells, it is not entirely clear which factors are responsible for priming of T cells to differentiate into Th2 effector cells in this disease. Interleukin (IL)-6 has been recognized as important because it is secreted by cells of the innate immunity and induces the expansion of the Th2 effector cells, which are major players of the adaptive immune responses. Additionally, IL-6 released by dendritic cells (DCs) inhibits the suppressive function of CD4+CD25+ T regulatory cells, thus inhibiting the peripheral tolerance. The signal transduction of IL-6 has recently taught us how this cytokine inf…