scholarly journals Proteomic Analysis of Urinary Extracellular Vesicles Reveals a Role for the Complement System in Medullary Sponge Kidney Disease

2019 ◽  
Vol 20 (21) ◽  
pp. 5517 ◽  
Author(s):  
Bruschi ◽  
Granata ◽  
Candiano ◽  
Fabris ◽  
Petretto ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Support Vector ◽  
Complement Pathway ◽  
Medullary Sponge Kidney ◽  
Diagnostic Biomarkers ◽  
Proteomic Data ◽  
Proteomics Approach ◽  
Complement Component 4 ◽  
Mannan Binding Lectin ◽  
The Complement System

Medullary sponge kidney (MSK) disease is a rare and neglected kidney condition often associated with nephrocalcinosis/nephrolithiasis and cystic anomalies in the precalyceal ducts. Little is known about the pathogenesis of this disease, so we addressed the knowledge gap using a proteomics approach. The protein content of microvesicles/exosomes isolated from urine of 15 MSK and 15 idiopathic calcium nephrolithiasis (ICN) patients was investigated by mass spectrometry, followed by weighted gene coexpression network analysis, support vector machine (SVM) learning, and partial least squares discriminant analysis (PLS-DA) to select the most discriminative proteins. Proteomic data were verified by ELISA. We identified 2998 proteins in total, 1764 (58.9%) of which were present in both vesicle types in both diseases. Among the MSK samples, only 65 (2.2%) and 137 (4.6%) proteins were exclusively found in the microvesicles and exosomes, respectively. Similarly, among the ICN samples, only 75 (2.5%) and 94 (3.1%) proteins were exclusively found in the microvesicles and exosomes, respectively. SVM learning and PLS-DA revealed a core panel of 20 proteins that distinguished extracellular vesicles representing each clinical condition with an accuracy of 100%. Among them, three exosome proteins involved in the lectin complement pathway maximized the discrimination between MSK and ICN: Ficolin 1, Mannan-binding lectin serine protease 2, and Complement component 4-binding protein β. ELISA confirmed the proteomic results. Our data show that the complement pathway is involved in the MSK, revealing a new range of potential therapeutic targets and early diagnostic biomarkers.

scholarly journals Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zihao Li ◽  
Mian Wang ◽  
Hua Zhong ◽  
Xin Huang ◽  
Xinyin Wu ◽  
...  
Keyword(s):  
Additive Model ◽  
Lectin Pathway ◽  
Control Group ◽  
Single Nucleotide ◽  
Key Enzyme ◽  
Healthy Control ◽  
Tea Drinking ◽  
Mannan Binding Lectin ◽  
The Complement System ◽  
Negative Interactions

AbstractMannan-binding lectin-associated serine protease-2 (MASP-2) has been reported to play an important role as a key enzyme in the lectin pathway of the complement system. The objectives of our study were to determine whether the single-nucleotide polymorphism (SNPs) of MASP2 and the gene-tea drinking interaction were associated with the susceptibility to TB. In total, 503 patients and 494 healthy controls were contained. Three SNPs (rs12142107, rs12711521, and rs7548659) were genotyped. The association between the SNPs and susceptibility to TB were investigated by conducting multivariate unconditional logistic regression analysis. The gene-tea drinking interactions were analyzed by the additive model of marginal structural linear odds models. Both genotype AC + AA at rs12711521 of MASP2 genes and genotype GT + GG at rs7548659 of MASP2 genes were more prevalent in the TB patient group than the healthy control group (OR: 1.423 and 1.439, respectively, P < 0.05). In addition, The relative excess risk of interaction (RERI) between tea drinking and rs12142107, rs12711521, and rs7548659 of MASP2 genes was found to suggest negative interactions, which reached − 0.2311 (95% confidence interval (CI): − 0.4736, − 0.0113), − 0.7080 (95% CI − 1.3998, − 0.0163), and − 0.5140 (95% CI − 0.8988, − 0.1291), respectively (P < 0.05). Our finding indicated that the SNPs (rs12711521 and rs7548659) of MASP2 were associated with the susceptibility to TB. Furthermore, there were negative interactions between tea drinking and rs12142107, rs12711521, and rs75548659 of MASP2 gene, respectively. Our research provides a basis for studying the pathogenesis and prevention of tuberculosis.

scholarly journals Simple Method To Distinguish between Primary and Secondary C3 Deficiencies

2003 ◽  
Vol 10 (2) ◽  
pp. 216-220
Author(s):  
Marlene Pereira de Carvalho Florido ◽  
Patrícia Ferreira de Paula ◽  
Lourdes Isaac
Keyword(s):  
Human Serum ◽  
Complement System ◽  
Factor H ◽  
Normal Human Serum ◽  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Factor B ◽  
Alternative Complement ◽  
Normal Human ◽  
The Complement System

ABSTRACT Due to the increasing numbers of reported clinical cases of complement deficiency in medical centers, clinicians are now more aware of the role of the complement system in the protection against infections caused by microorganisms. Therefore, clinical laboratories are now prepared to perform a number of diagnostic tests of the complement system other than the standard 50% hemolytic component assay. Deficiencies of alternative complement pathway proteins are related to severe and recurrent infections; and the application of easy, reliable, and low-cost methods for their detection and distinction are always welcome, notably in developing countries. When activation of the alternative complement pathway is evaluated in hemolytic agarose plates, some but not all human sera cross-react to form a late linear lysis. Since the formation of this linear lysis is dependent on C3 and factor B, it is possible to use late linear lysis to routinely screen for the presence of deficiencies of alternative human complement pathway proteins such as factor B. Furthermore, since linear lysis is observed between normal human serum and primary C3-deficient serum but not between normal human serum and secondary C3-deficient serum caused by the lack of factor H or factor I, this assay may also be used to discriminate between primary and secondary C3 deficiencies.

scholarly journals Enrichment of Exosome-Like Extracellular Vesicles from Plasma Suitable for Clinical Vesicular miRNA Biomarker Research

2019 ◽  
Vol 8 (11) ◽  
pp. 1995 ◽  
Author(s):  
Moon ◽  
Shin ◽  
Kim ◽  
Lee ◽  
Mankhong ◽  
...  
Keyword(s):  
Human Plasma ◽  
Extracellular Vesicles ◽  
Proteinase K ◽  
High Yield ◽  
Clinical Samples ◽  
Diagnostic Biomarkers ◽  
Micro Rnas ◽  
Biomarker Research ◽  
Protein Rich ◽  
Yield And Purity

Exosome-like extracellular vesicles (ELVs) contain biomolecules that have potential as diagnostic biomarkers, such as proteins, micro-RNAs (miRNAs), and lipids. However, it is difficult to enrich ELVs consistently with high yield and purity from clinical samples, which hampers the development of ELV biomarkers. This is particularly true for miRNAs in protein-rich plasma. Hence, we modified ELV isolation protocols of three commercially available polymer-precipitation-based kits using proteinase K (PK) treatment to quantify ELV-associated miRNAs in human plasma. We compared the yield, purity, and characteristics of enriched plasma ELVs, and measured the relative quantity of three selected miRNAs (miR-30c, miR-126, and miR-192) in ELVs using six human plasma samples. Compared with the original protocols, we demonstrated that ELVs can be isolated with PK treatment with high purity (i.e., lack of non-exosomal proteins and homogeneous size of vesicles) and yield (i.e., abundancy of exosomal markers), which were dependent on kits. Using the kit with the highest purity and yield with PK treatment, we successfully quantified ELV miRNAs (levels of 45%–65% in total plasma) with acceptable variability. Collectively, ELV enrichment using the modified easy-to-use method appears suitable for the analysis of miRNAs, although its clinical applicability needs to be confirmed in larger clinical studies.

scholarly journals Mannan-binding lectin activates C3 and the alternative complement pathway without involvement of C2

2007 ◽  
Vol 44 (1-3) ◽  
pp. 238
Author(s):  
Barbro Selander ◽  
Ulla Mårtensson ◽  
Andrej Weintraub ◽  
Eva Holmström ◽  
Misao Matsushita ◽  
...  
Keyword(s):  
Alternative Complement Pathway ◽  
Complement Pathway ◽  
Alternative Complement ◽  
Mannan Binding Lectin ◽  
Binding Lectin

scholarly journals A panel of miRNAs derived from plasma extracellular vesicles as novel diagnostic biomarkers of lung adenocarcinoma

FEBS Open Bio ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 2149-2158 ◽  
Author(s):  
Bing Yao ◽  
Shuang Qu ◽  
Ruifeng Hu ◽  
Wen Gao ◽  
Shidai Jin ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Extracellular Vesicles ◽  
Diagnostic Biomarkers

scholarly journals Integrative brain transcriptome analysis links complement component 4 and HSPA2 to the APOE ε2 protective effect in Alzheimer disease

2021 ◽  
Author(s):  
Rebecca Panitch ◽  
Junming Hu ◽  
Jaeyoon Chung ◽  
Congcong Zhu ◽  
Gaoyuan Meng ◽  
...  
Keyword(s):  
Alzheimer Disease ◽  
Protective Effect ◽  
Amyloid Β ◽  
Oligodendrocyte Progenitor Cells ◽  
Expression Data ◽  
Complement Pathway ◽  
Tau Pathology ◽  
Brain Transcriptome ◽  
Complement Component 4

AbstractMechanisms underlying the protective effect of apolipoprotein E (APOE) ε2 against Alzheimer disease (AD) are not well understood. We analyzed gene expression data derived from autopsied brains donated by 982 individuals including 135 APOE ɛ2/ɛ3 carriers. Complement pathway genes C4A and C4B were among the most significantly differentially expressed genes between ɛ2/ɛ3 AD cases and controls. We also identified an APOE ε2/ε3 AD-specific co-expression network enriched for astrocytes, oligodendrocytes and oligodendrocyte progenitor cells containing the genes C4A, C4B, and HSPA2. These genes were significantly associated with the ratio of phosphorylated tau at position 231 to total Tau but not with amyloid-β 42 level, suggesting this APOE ɛ2 related co-expression network may primarily be involved with tau pathology. HSPA2 expression was oligodendrocyte-specific and significantly associated with C4B protein. Our findings provide the first evidence of a crucial role of the complement pathway in the protective effect of APOE ε2 for AD.

scholarly journals Heme Interacts with C1q and Inhibits the Classical Complement Pathway

2011 ◽  
Vol 286 (18) ◽  
pp. 16459-16469 ◽  
Author(s):  
Lubka T. Roumenina ◽  
Maria Radanova ◽  
Boris P. Atanasov ◽  
Krastio T. Popov ◽  
Srinivas V. Kaveri ◽  
...  
Keyword(s):  
Tissue Damage ◽  
Negative Regulator ◽  
Complement Pathway ◽  
Classical Complement Pathway ◽  
Reactive Protein ◽  
Free Heme ◽  
Direct Binding ◽  
Mechanism Of Recognition ◽  
The Complement System ◽  
Classical Complement

C1q is the recognition subunit of the first component of the classical complement pathway. It participates in clearance of immune complexes and apoptotic cells as well as in defense against pathogens. Inappropriate activation of the complement contributes to cellular and tissue damage in different pathologies, urging the need for the development of therapeutic agents that are able to inhibit the complement system. In this study, we report heme as an inhibitor of C1q. Exposure of C1q to heme significantly reduced the activation of the classical complement pathway, mediated by C-reactive protein (CRP) and IgG. Interaction analyses revealed that heme reduces the binding of C1q to CRP and IgG. Furthermore, we demonstrated that the inhibition of C1q interactions results from a direct binding of heme to C1q. Formation of complex of heme with C1q caused changes in the mechanism of recognition of IgG and CRP. Taken together, our data suggest that heme is a natural negative regulator of the classical complement pathway at the level of C1q. Heme may play a role at sites of excessive tissue damage and hemolysis where large amounts of free heme are released.

Sign in / Sign up

Export Citation Format

Share Document