Dataset Information

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations.

ABSTRACT: Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephritic factor has been characterized by the ability to stabilize C5 convertase of the alternative pathway (C5NeF). In addition, there are autoantibodies against assembled C3/C5 convertase of the classical and lectin pathways (C4NeF). These autoantibodies have been mainly associated with kidney diseases, like C3 glomerulopathy and immune complex-associated-membranoproliferative glomerulonephritis. Other clinical situations where these autoantibodies have been observed include infections and autoimmune disorders such as systemic lupus erythematosus and acquired partial lipodystrophy. C3 hypocomplementemia is a common finding in all patients with nephritic factors. The methods to measure nephritic factors are not standardized, technically complex, and lack of an appropriate quality control. This review will be focused in the description of the mechanism of action of the three known nephritic factors (C3NeF, C4NeF, and C5NeF), and their association with human diseases. Moreover, we present an overview regarding the diagnostic tools for its detection, and the main therapeutic approach for the patients with nephritic factors.

SUBMITTER: Corvillo F

PROVIDER: S-EPMC6491685 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations.

Corvillo Fernando F Okrój Marcin M Nozal Pilar P Melgosa Marta M Sánchez-Corral Pilar P López-Trascasa Margarita M

Frontiers in immunology 20190424

Nephritic factors comprise a heterogeneous group of autoantibodies against neoepitopes generated in the C3 and C5 convertases of the complement system, causing its dysregulation. Classification of these autoantibodies can be clustered according to their stabilization of different convertases either from the classical or alternative pathway. The first nephritic factor described with the capacity to stabilize C3 convertase of the alternative pathway was C3 nephritic factor (C3NeF). Another nephrit ...[more]

PMID: 31068950

Similar Datasets

Project description:ObjectiveCurrent studies lack a comprehensive understanding of the environmental factors influencing type 2 diabetes, hindering an in-depth grasp of the overall etiology. To address this gap, we utilized network science tools to highlight research trends, knowledge structures, and intricate relationships among factors, offering a new perspective for a profound understanding of the etiology.MethodsThe Web of Science database was employed to retrieve documents relevant to environmental risk factors in type 2 diabetes from 2012 to 2024. Bibliometric analysis using Microsoft Excel and OriginPro provided a detailed scientific production profile, including articles, journals, countries, and authors. Co-occurrence analysis was employed to determine the collaboration state and knowledge structures, utilizing social network tools such as Gephi, Tableau, and R Studio. Additionally, theme evolutionary analysis was conducted using SciMAT to offer insights into research trends.ResultsThe publications and themes related to environmental factors in type 2 diabetes have consistently risen, shaping a well-established research domain. Lifestyle environmental factors, particularly diet and nutrition, stand out as the most represented and rapidly growing topics. Key focal hotspots include sedentary and digital behavior, PM2.5, ethnicity and socioeconomic status, traffic and greenspace, and depression. The theme evolutionary analysis revealed three distinct paths: (1) oxidative stress-air pollutants-PM2.5-air pollutants; (2) calcium-metabolic syndrome-cardiovascular disease; and (3) polychlorinated biphenyls (PCBs)-persistent organic pollutants (POPs)-obesity.ConclusionsDigital behavior signifies a novel approach for preventing and managing type 2 diabetes. The influence of PM2.5 and calcium on oxidative stress and abnormal vascular contraction is intricately linked to microvascular diabetes complications. The transition from PCBs and POPs to obesity underscores the disruption of endocrine function by chemicals, elevating the risk of diabetes. Future studies should explore the connections between environmental factors, microvascular complications, and long-term outcomes in diabetes.

Project description:Membranoproliferative glomerulonephritis (MPGN) was recently classified as C3 glomerulopathies (C3G), and immune-complex (IC) mediated MPGN. Dysregulation of the complement alternative pathway, driven by acquired and/or genetic defects, plays a pathogenetic role in C3G. However, alternative pathway abnormalities were also found in IC-MPGN. The most common acquired drivers are the C3 nephritic factors (C3NeFs), heterogeneous autoantibodies that stabilize the C3 convertase, C3bBb. C3NeFs are traditionally detected by hemolytic assays based on sheep erythrocyte lysis, which however do not provide a direct molecular estimation of C3bBb formation and decay. We set up a microplate/western blot assay that specifically detects and quantifies C3bBb, and its precursor, the C3 proconvertase C3bB, to investigate the complex mechanistic effects of C3NeFs from patients with primary IC-MPGN (n = 13) and C3G (n = 13). In the absence of properdin, 9/26 patients had C3NeF IgGs stabilizing C3bBb against spontaneous and FH-accelerated decay. In the presence of properdin the IgGs of all but one patient had C3bBb-stabilizing activity. Properdin-independent C3NeFs were identified mostly in DDD patients, while properdin-dependent C3NeFs associated with either C3GN or IC-MPGN and with higher incidence of nephrotic syndrome. When we grouped patients based on our recent cluster analysis, patients in cluster 3, with highly electron-dense intramembranous deposits, low C3, and mostly normal sC5b-9 levels, had a higher prevalence of properdin-independent C3NeFs than patients in clusters 1 and 2. Conversely, about 70% of cluster 1 and 2 patients, with subendothelial, subepithelial, and mesangial deposits, low C3 levels and high sC5b-9 levels, had properdin-dependent C3NeFs. The flexibility of the assay allowed us to get deep insights into C3NeF mechanisms of action, showing that: (1) most C3NeFs bind strongly and irreversibly to C3 convertase; (2) C3NeFs and FH recognize different epitopes in C3 convertase; (3) C3NeFs bind rapidly to C3 convertase and antagonize the decay accelerating activity of FH on newly formed complexes; (4) C3NeFs do not affect formation and stability of the C3 proconvertase. Thus, our study provides a molecular approach to detecting and characterizing C3NeFs. The results highlight different mechanisms of complement dysregulation resulting in different complement profiles and patterns of glomerular injury, and this may have therapeutic implications.

Project description:INTRODUCTION:Recanalisation therapy in acute ischaemic stroke is highly time-sensitive, and requires early identification of eligible patients to ensure better outcomes. Thus, a number of clinical assessment tools have been developed and this review examines their diagnostic capabilities. METHODS:Diagnostic performance of currently available clinical tools for identification of acute ischaemic and haemorrhagic strokes and stroke mimicking conditions was reviewed. A systematic search of the literature published in 2015-2018 was conducted using PubMed, EMBASE, Scopus and The Cochrane Library. Prehospital and in-hospital studies with a minimum sample size of 300 patients reporting diagnostic accuracy were selected. RESULTS:Twenty-five articles were included. Cortical signs (gaze deviation, aphasia and neglect) were shown to be significant indicators of large vessel occlusion (LVO). Sensitivity values for selecting subjects with LVO ranged from 23 to 99% whereas specificity was 24 to 97%. Clinical tools, such as FAST-ED, NIHSS, and RACE incorporating cortical signs as well as motor dysfunction demonstrated the best diagnostic accuracy. Tools for identification of stroke mimics showed sensitivity varying from 44 to 91%, and specificity of 27 to 98% with the best diagnostic performance demonstrated by FABS (90% sensitivity, 91% specificity). Hypertension and younger age predicted intracerebral haemorrhage whereas history of atrial fibrillation and diabetes were associated with ischaemia. There was a variation in approach used to establish the definitive diagnosis. Blinding of the index test assessment was not specified in about 50% of included studies. CONCLUSIONS:A wide range of clinical assessment tools for selecting subjects with acute stroke has been developed in recent years. Assessment of both cortical and motor function using RACE, FAST-ED and NIHSS showed the best diagnostic accuracy values for selecting subjects with LVO. There were limited data on clinical tools that can be used to differentiate between acute ischaemia and haemorrhage. Diagnostic accuracy appeared to be modest for distinguishing between acute stroke and stroke mimics with optimal diagnostic performance demonstrated by the FABS tool. Further prehospital research is required to improve the diagnostic utility of clinical assessments with possible application of a two-step clinical assessment or involvement of simple brain imaging, such as transcranial ultrasonography.

Dataset Information

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations.

Publications

Nephritic Factors: An Overview of Classification, Diagnostic Tools and Clinical Associations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets