scholarly journals Effect of IgG from multiple sclerosis patients on amidolytic activity of coagulation and anticoagulation factors of hemostasis

2017 ◽  
Vol 4 (08) ◽  
pp. 1502
Author(s):  
Katrii T.B. ◽  
Shandyuk V.Yu. ◽  
Vovk T.B. ◽  
Halenova T.I. ◽  
Raksha N.G. ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Protein C ◽  
Factor Xa ◽  
Coagulation Factors ◽  
Therapeutic Strategies ◽  
Healthy Individuals ◽  
Amidolytic Activity ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients ◽  
Hydrolysis Of

Background: Immunoglobulin G (IgG) is a major immunoglobulin (Ig) in blood that accumulates to a greater extent in the bloodstream of patients impacted by neuroimmunological disorders such as multiple sclerosis (MS). The aim of this study was to determine the effect of IgG obtained from MS patients on the amidolytic activity of coagulation and on anticoagulation factors, and to compare those effects to the effects of IgG from healthy donors. Methods: Spectrophotometric hydrolysis of specific chromogenic substrate by key haemostasis factors was examined. Results: Our study shows that unlike healthy individuals, patients suffering from MS express IgG which enhances the amidolytic activity of thrombin and protein C, but inhibits the activity of factor Xa. Conclusion: Our study shows that IgG and coagulation factors, indeed, interact with each other. IgG may be key mediators of neuroinflammation and, therefore, may serve as a potential target for therapeutic strategies for MS and other neuroimmunological diseases.

scholarly journals Cryo-EM structures of human coagulation factors V and Va

Blood ◽  
2021 ◽  
Author(s):  
Eliza A Ruben ◽  
Michael J Rau ◽  
James Fitzpatrick ◽  
Enrico Di Cera
Keyword(s):  
Protein C ◽  
Activated Protein C ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Proteolytic Processing ◽  
Coagulation Cascade ◽  
Factor V ◽  
Prothrombinase Complex ◽  
A2 Domain

Coagulation factor V is the precursor of factor Va that, together with factor Xa, Ca2+ and phospholipids, defines the prothrombinase complex and activates prothrombin in the penultimate step of the coagulation cascade. Here we present cryo-EM structures of human factors V and Va at atomic (3.3 Å) and near-atomic (4.4 Å) resolution, respectively. The structure of fV reveals the entire A1-A2-B-A3-C1-C2 assembly but with a surprisingly disordered B domain. The C1 and C2 domains provide a platform for interaction with phospholipid membranes and support the A1 and A3 domains, with the A2 domain sitting on top of them. The B domain is highly dynamic and visible only for short segments connecting to the A2 and A3 domains. The A2 domain reveals all sites of proteolytic processing by thrombin and activated protein C, a partially buried epitope for binding factor Xa and fully exposed epitopes for binding activated protein C and prothrombin. Removal of the B domain and activation to fVa exposes the sites of cleavage by activated protein C at R306 and R506 and produces increased disorder in the A1-A2-A3-C1-C2 assembly, especially in the C-terminal acidic portion of the A2 domain responsible for prothrombin binding. Ordering of this region and full exposure of the factor Xa epitope emerge as a necessary step for the assembly of the prothrombin-prothrombinase complex. These structures offer molecular context for the function of factors V and Va and pioneer the analysis of coagulation factors by cryo-EM.

scholarly journals Phenotypic and Ig Repertoire Analyses Indicate a Common Origin of IgD−CD27− Double Negative B Cells in Healthy Individuals and Multiple Sclerosis Patients

2019 ◽  
Vol 203 (6) ◽  
pp. 1650-1664 ◽  
Author(s):  
Judith Fraussen ◽  
Susanna Marquez ◽  
Kazushiro Takata ◽  
Lien Beckers ◽  
Gwendoline Montes Diaz ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
Common Origin ◽  
Double Negative ◽  
Healthy Individuals ◽  
Multiple Sclerosis Patients

scholarly journals Association of CD58 polymorphism and multiple sclerosis in Malaysia: a pilot study

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Yee Ming Ching ◽  
Shanthi Viswanathan ◽  
Nurhanani Mohamed Nor ◽  
Shuwahida Shuib ◽  
Balqis Kamarudin ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Pilot Study ◽  
Gene Polymorphism ◽  
Age Of Onset ◽  
Nucleotide Polymorphisms ◽  
Healthy Individuals ◽  
Disease Manifestation ◽  
Southeast Asians ◽  
Multiple Sclerosis Patients ◽  
The Impact

Abstract Background Multiple sclerosis is an immune mediated disease targeting the central nervous system. Association of non-human leukocyte antigen gene, CD58, with multiple sclerosis has been reported in several populations but is unclear among Southeast Asians. This pilot study was conducted to explore the association between CD58 polymorphism and multiple sclerosis among the Malay population in Malaysia. Methods Blood samples were collected from 27 multiple sclerosis patients, and compared with 58 age- and gender matched healthy individuals. All patients were tested negative for anti-aquaporin 4. DNA was extracted from the blood and genotyped for 3 single nucleotide polymorphisms rs12044852, rs2300747 and rs1335532 of gene CD58 by real-time PCR. Results The majority of multiple sclerosis patients were female (85.2%). The general mean age of onset was 30.5 years. Genotyping results showed that frequencies of the alleles were between 40 and 50% for MS patients and healthy individuals. Association (allelic model) between multiple sclerosis and CD58 gene polymorphism alleles rs12044852 (p = 0.410), rs2300747 (p = 0.881) and rs1335532 (p = 0.407) were indistinct. Conclusions The impact of the CD58 gene polymorphism was not prominent in this pilot study, implying that genetic composition contributing to multiple sclerosis may be different between different populations, thus results in a heterogeneity of disease manifestation and distribution.

CCL2 induction by 1,25(OH)2D3 in dendritic cells from healthy donors and multiple sclerosis patients

2014 ◽  
Vol 144 ◽  
pp. 102-105 ◽  
Author(s):  
Isabella Sanseverino ◽  
Arturo O. Rinaldi ◽  
Cristina Purificato ◽  
Antonio Cortese ◽  
Enrico Millefiorini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dendritic Cells ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients

scholarly journals Immunomodulatory Potential of Human Mesenchymal Stem Cells and their Exosomes on Multiple Sclerosis

2021 ◽  
Author(s):  
Hussein Baharlooi ◽  
Zahra Salehi ◽  
Moein Minbashi Moeini ◽  
Nima Rezaei ◽  
Maryam Azimi
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Interleukin 17 ◽  
Healthy Individuals ◽  
Healthy Control ◽  
Multiple Sclerosis Patients

Purpose: Promising advances have been made in mesenchymal stem cell transplantation to re-induce the immune tolerance in neuroinflammatory animal models and Multiple Sclerosis patients. The available evidence demonstrated that immunomodulatory effects of mesenchymal stem cell are particularly exerted through releasing exosomes to their environment. We therefore, aimed to comparatively assess the potential effect of mesenchymal stem cells and mesenchymal stem cells-derived exosomes on proliferation and function of the CD4+CD25− conventional T cells, isolated from relapsing-remitting Multiple Sclerosis patients. Methods: Mesenchymal stem cells were isolated from human umbilical cord tissues and used for exosome isolation via ultracentrifugation. Both mesenchymal stem cells and mesenchymal stem cells-derived exosomes were evaluated for their anti-inflammatory effects against the proliferation of T cells isolated from two groups of individuals in vitro, MS patients and healthy subjects. Cytokine production of conventional T cells (interferon-γ, interleukin-10, and interleukin-17) was also assessed, using flow cytometry for the patients and healthy individuals. Results: Here, evidence shows that MSCs and MSC-derived exosomes dampen proliferation and percentage of conventional T cells that produce IFN-γ (healthy control: p<0.001) and interleukin-17 (healthy control: p<0.001, MS patients: p<0.001), with a significant increase of IL-10 producing cells in the patients and healthy individuals. Surprisingly, MSC-derived exosomes demonstrated higher immune-modulating properties on conventional T cells responses, compared to MSCs. Conclusion: The current study, provides a novel approach of exocytosis on autoimmune therapy. In particular, Mesenchymal stem cell -derived exosomes, which are cell-derived biologics, could be considered as an alternative for Mesenchymal stem cells in treating multiple sclerosis.

scholarly journals Distinct Expression of Inflammatory Features in T Helper 17 Cells from Multiple Sclerosis Patients

Cells ◽  
2019 ◽  
Vol 8 (6) ◽  
pp. 533 ◽  
Author(s):  
Alessia Capone ◽  
Manuela Bianco ◽  
Gabriella Ruocco ◽  
Marco De Bardi ◽  
Luca Battistini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cd4 T Cells ◽  
Th17 Cells ◽  
Chronic Inflammatory Disease ◽  
T Helper ◽  
T Helper 17 ◽  
Inflammatory Status ◽  
Healthy Donors ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS). T helper (Th) 17 lymphocytes play a role in the pathogenesis of MS. Indeed, Th17 cells are abundant in the cerebrospinal fluid and peripheral blood of MS patients and promote pathogenesis in the mouse model of MS. To gain insight into the function of Th17 cells in MS, we tested whether Th17 cells polarized from naïve CD4 T cells of healthy donors and MS patients display different features. To this end, we analysed several parameters that typify the Th17 profile during the differentiation process of naïve CD4 T cells obtained from relapsing-remitting (RR)-MS patients (n = 31) and healthy donors (HD) (n = 28). Analysis of an array of cytokines produced by Th17 cells revealed that expression of interleukin (IL)-21, tumour necrosis factor (TNF)-β, IL-2 and IL-1R1 is significantly increased in Th17 cells derived from MS patients compared to healthy donor-derived cells. Interestingly, IL-1R1 expression is also increased in Th17 cells circulating in the blood of MS patients compared to healthy donors. Since IL-2, IL-21, TNF-β, and IL-1R1 play a crucial role in the activation of immune cells, our data indicate that high expression of these molecules in Th17 cells from MS patients could be related to their high inflammatory status.

Prospects For Chromogenic And Fluorogenic Substrate Use In Biochemistry And Blood Protease Assay

1981 ◽  
Author(s):  
Craiq M Jackson
Keyword(s):  
Activated Protein C ◽  
Factor Xa ◽  
Maximum Velocity ◽  
Peptide Bond ◽  
Coagulation Factors ◽  
Specific Information ◽  
Fluorogenic Substrates ◽  
Multiple Substrate ◽  
Multifunctional Molecules ◽  
Hydrolysis Of

Kinetic parameters describing the hydrolysis of peptide p-nitroanilide substrates by thrombin, Factor Xa, and activated Protein C indicate that a high degree of selectivity for each of these proteases can be achieved by using appropriate substrates. Determination of kcat (the maximum velocity per mole of enzyme) for peptide p-nitroanilide substrates indicates that sensitivity sufficient to detect pM concentrations of these proteases can be obtained. The use of fluorogenic substrates should increase sensitivity, although the absence of data for maximum velocities of hydrolysis of peptide fluorogenic substrates precludes quantitative statements about the extent of increase in sensitivity that may actually be obtained. The use of more than one substrate provides an opportunity to selectively assay individual enzymes present in a mixture of proteases. The selectivity of the various assays can be enhanced by use of competitive inhibitors such as those developed in several laboratories for use as potential antithrombotic agents. Although manual methods may be too tedious to be practical in complex situations, the automated methods which handle multiple samples can make such multiple-substrate based assay methods practical. The fact that a single function of the protease coagulation factors, namely the peptide bond hydrolysis function is being assessed by peptide chromogenic and fluorogenic substrates will permit more specific information to be obtained about these multifunctional molecules.

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