Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The Potential Role of an Aberrant Mucosal Immune Response to SARS-CoV-2 in the Pathogenesis of IgA Nephropathy.

ABSTRACT: The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global concern. Immunoglobin A (IgA) contributes to virus neutralization at the early stage of infection. Longitudinal studies are needed to assess whether SARS-CoV-2-specific IgA production persists for a longer time in patients recovered from severe COVID-19 and its lasting symptoms that can have disabling consequences should also be alerted to susceptible hosts. Here, we tracked the anti-SARS-CoV-2 spike protein receptor-binding domain (RBD) antibody levels in a cohort of 88 COVID-19 patients. We found that 52.3% of the patients produced more anti-SARS-CoV-2 RBD IgA than IgG or IgM, and the levels of IgA remained stable during 4-41 days of infection. One of these IgA-dominant COVID-19 patients, concurrently with IgA nephropathy (IgAN), presented with elevated serum creatinine and worse proteinuria during the infection, which continued until seven months post-infection. The serum levels of anti-SARS-CoV-2 RBD and total IgA were higher in this patient than in healthy controls. Changes in the composition of the intestinal microbiota, increased IgA highly coated bacteria, and elevated concentration of the proinflammatory cytokine IL-18 were indicative of potential involvement of intestinal dysbiosis and inflammation to the systemic IgA level and, consequently, the disease progression. Collectively, our work highlighted the potential adverse effect of the mucosal immune response to SARS-CoV-2 infection, and that additional care should be taken with COVID-19 patients presenting with chronic diseases such as IgAN.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC8308514 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Mucosal Immune System Dysregulation in the Pathogenesis of IgA Nephropathy.

Project description:The mucosal immune system, via a dynamic immune network, serves as the first line of defense against exogenous antigens. Mucosal immune system dysregulation is closely associated with the pathogenesis of immunoglobulin A nephropathy (IgAN), as illustrated by IgAN having the clinical feature of gross hematuria, often concurrent with mucosal infections. Notably, previous studies have demonstrated the efficacy of tonsillectomy and found that a targeted-release formulation of budesonide reduced proteinuria in patients with IgAN. However, it remains unclear how exogenous antigens interact with the mucosal immune system to induce or exacerbate IgAN. Thus, in this review, we focus on the dysregulation of mucosal immune response in the pathogenesis of IgAN.

| S-EPMC9775168 | biostudies-literature

The Role of Immune Modulation in Pathogenesis of IgA Nephropathy.

Project description:IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide, with diverse clinical manifestations characterized by recurrent gross hematuria or microscopic hematuria, and pathological changes featuring poorly O-galactosylated IgA1 deposition in the glomerular mesangium. Pathogenesis has always been the focus of IgAN studies. After 50 years of research, most scholars agree that IgAN is a group of clinicopathological syndromes with certain common immunopathological characteristics, and multiple mechanisms are involved in its pathogenesis, including immunology, genetics, and environmental or nutritional factors. However, the precise pathogenetic mechanisms have not been fully determined. One hypothesis about the pathogenesis of IgAN suggests that immunological factors are engaged in all aspects of IgAN development and play a critical role. A variety of immune cells (e.g., dendritic cells, NK cells, macrophages, T-lymphocyte subsets, and B-lymphocytes, etc.) and molecules (e.g., IgA receptors, Toll-like receptors, complements, etc.) in innate and adaptive immunity are involved in the pathogenesis of IgAN. Moreover, the abnormality of mucosal immune regulation is the core of IgAN immunopathogenesis. The roles of tonsil immunity or intestinal mucosal immunity, which have received more attention in recent years, are supported by mounting evidence. In this review, we will explore the latest research insights on the role of immune modulation in the pathogenesis of IgAN. With a better understanding of immunopathogenesis of IgAN, emerging therapies will soon become realized.

| S-EPMC7105732 | biostudies-literature

Role of aberrant glycosylation of IgA1 molecules in the pathogenesis of IgA nephropathy.

Project description:Studies of the properties of immune complexes (IC) in the circulation, urine, and mesangium of IgA nephropathy (IgAN) patients have provided data relevant to the pathogenesis of this disease. IC contain predominantly polymeric IgA1 molecules which are deficient in galactose (Gal) residues on O-linked glycan chains in the hinge region (HR) of their heavy (H) chains. As a result of this aberrancy, a novel antigenic determinant(s) involving N-acetylgalactosamine (GalNAc) and perhaps sialic acid (SA) of O-linked glycans is generated and recognized by naturally occurring GalNAc-specific antibodies. Thus, IC in IgAN consist of Gal-deficient IgA1 molecules as an antigen, and GalNAc-specific IgG and/or IgA1 as an antibody. IgG antibodies to Gal-deficient IgA1 are probably induced by cross-reactive microbial antigens; they are present at variable levels not only in humans with or without IgAN but also in many phylogenetically diverse vertebrate species. Incubation of human mesangial cells with IC from sera of IgAN patients indicated that stimulation of cellular proliferative activity was restricted to the large (>800 kDa) complexes. These findings suggest that experimental approaches that prevent the formation of large Gal-deficient IgA1-IgG IC may be applied ultimately in an immunologically mediated therapy.

| S-EPMC2821435 | biostudies-literature

The mucosal immune system and IgA nephropathy.

Project description:The precise pathogenesis of immunoglobulin A nephropathy (IgAN) is still not clearly established but emerging evidence confirms a pivotal role for mucosal immunity. This review focuses on the key role of mucosa-associated lymphoid tissue (MALT) in promoting the onset of the disease, underlying the relationship among microbiota, genetic factors, food antigen, infections, and mucosal immune response. Finally, we evaluate potential therapies targeting microbes and mucosa hyperresponsiveness in IgAN patients.

| S-EPMC8551125 | biostudies-literature

The Role of IgA in the Pathogenesis of IgA Nephropathy.

Project description:Immunoglobulin A (IgA) is the most abundant antibody isotype produced in humans, predominantly present in the mucosal areas where its main functions are the neutralization of toxins, prevention of microbial invasion across the mucosal epithelial barrier, and simultaneous maintenance of a physiologically indispensable symbiotic relationship with commensal bacteria. The process of IgA biosynthesis, interaction with receptors, and clearance can be disrupted in certain pathologies, like IgA nephropathy, which is the most common form of glomerulonephritis worldwide. This review summarizes the latest findings in the complex characteristics of the molecular structure and biological functions of IgA antibodies, offering an in-depth overview of recent advances in the understanding of biochemical, immunologic, and genetic factors important in the pathogenesis of IgA nephropathy.

| S-EPMC6940854 | biostudies-literature

The role of microRNAs in the pathogenesis of IgA nephropathy

Project description:We report the expression of microRNAs in renal biopsies from patients with IgA nephropathy (progressive form and non progressive form), membranous and thin membrane nephropathies

2021-02-23 | GSE141344 | GEO

What Genetics Tells Us About the Pathogenesis of IgA Nephropathy: The Role of Immune Factors and Infection.

Project description:Immunoglobulin A nephropathy (IgAN) is the most common type of primary glomerulonephritis, which is characterized by IgA1-containing immune-deposits in the glomerular mesangium. The epidemiologic observations of familial clustering as well as ethnic and regional discrepancies indicate a genetic component to IgAN. Large, international, genome-wide association studies have identified several susceptibility genes and loci for IgAN, many of which have been implicated in immune regulation and are shared with other autoimmune diseases. Notably, increasing numbers of genes involved in mucosal immunity have been detected; such genes may impact the susceptibility and progression of IgAN through interaction with environmental stimuli (especially infection). Here, we discuss the innate and adaptive immune mechanisms that drive protective immunity against pathogens. Our goal is to provide a representative overview of the synergistic roles between genetic predisposition and infection in IgAN pathogenesis. We anticipate that these results will provide potential therapeutic agents and advances in precision medicine.

| S-EPMC5678660 | biostudies-literature

Role of Epstein-Barr Virus in Pathogenesis and Racial Distribution of IgA Nephropathy.

Project description:IgA nephropathy (IgAN) is the dominant type of primary glomerulonephritis worldwide. However, IgAN rarely affects African Blacks and is uncommon in African Americans. Polymeric IgA1 with galactose-deficient hinge-region glycans is recognized as auto-antigen by glycan-specific antibodies, leading to formation of circulating immune complexes with nephritogenic consequences. Because human B cells infected in vitro with Epstein-Barr virus (EBV) secrete galactose-deficient IgA1, we examined peripheral blood B cells from adult IgAN patients, and relevant controls, for the presence of EBV and their phenotypic markers. We found that IgAN patients had more lymphoblasts/plasmablasts that were surface-positive for IgA, infected with EBV, and displayed increased expression of homing receptors for targeting the upper respiratory tract. Upon polyclonal stimulation, these cells produced more galactose-deficient IgA1 than did cells from healthy controls. Unexpectedly, in healthy African Americans, EBV was detected preferentially in surface IgM- and IgD-positive cells. Importantly, most African Blacks and African Americans acquire EBV within 2 years of birth. At that time, the IgA system is naturally deficient, manifested as low serum IgA levels and few IgA-producing cells. Consequently, EBV infects cells secreting immunoglobulins other than IgA. Our novel data implicate Epstein-Barr virus infected IgA+ cells as the source of galactose-deficient IgA1 and basis for expression of relevant homing receptors. Moreover, the temporal sequence of racial-specific differences in Epstein-Barr virus infection as related to the naturally delayed maturation of the IgA system explains the racial disparity in the prevalence of IgAN.

| S-EPMC7058636 | biostudies-literature

Secondary IgA Nephropathy Shares the Same Immune Features With Primary IgA Nephropathy.

Project description:IntroductionGalactose-deficient IgA1 (Gd-IgA1) and related IgA/IgG immune complexes have been identified as the key drivers in the pathogenesis of IgA nephropathy (IgAN). However, their roles in the development of secondary IgAN are still unknown.MethodsIn this study, we measured the plasma Gd-IgA1 level, IgA/IgG complex, and Gd-IgA1 glomerular deposits in 100 patients with various kinds of secondary IgAN. Plasma Gd-IgA1 was measured using a lectin-based enzyme-linked immunosorbent assay, and Gd-IgA1 in glomerular deposits was examined by double immunofluorescent staining using its specific monoclonal antibody KM55.ResultsPatients with secondary IgAN presented with higher plasma Gd-IgA1 levels compared to healthy controls (median, 354.61 U/ml; interquartile range [IQR], 323.93, 395.57 U/ml vs. median, 303.17 U/ml; IQR, 282.24, 337.92 U/ml, P < 0.001) or patients with other kidney diseases (median, 314.61 U/ml; IQR, 278.97, 343.55 U/ml, P < 0.001). A similar trend was observed in plasma IgA/IgG immune complexes or IgA1. There were no differences between secondary and primary IgAN in plasma Gd-IgA1 levels (median, 378.54 U/ml; IQR, 315.96, 398.33 U/ml, P = 0.700) and IgA1-IgG complex levels (median, 18.76 U/ml; IQR, 14.51, 22.83 U/ml vs. median, 19.11 U/ml; IQR, 13.21, 22.37 U/ml, P = 0.888). Co-localized IgA1 and Gd-IgA1 of both secondary and primary IgAN indicated that they both share the feature of Gd-IgA1 deposits on the glomerular mesangium.ConclusionOur study strongly suggests that secondary IgAN shares a similar galactose-deficient IgA1-oriented pathogenesis with primary IgAN.

| S-EPMC7000803 | biostudies-literature

Aberrant Glycosylation of the IgA1 Molecule in IgA Nephropathy.

Project description:IgA nephropathy, the most common primary glomerulonephritis in the world and a frequent cause of end-stage renal disease, is characterized by typical mesangial deposits of IgA1, as described by Berger and Hinglaise in 1968. Since then, it has been discovered that aberrant IgA1 O-glycosylation is involved in disease pathogenesis. Progress in glycomic, genomic, clinical, analytical, and biochemical studies has shown autoimmune features of IgA nephropathy. The autoimmune character of the disease is explained by a multihit pathogenesis model, wherein overproduction of aberrantly glycosylated IgA1, galactose-deficient in some O-glycans, by IgA1-secreting cells leads to increased levels of circulatory galactose-deficient IgA1. These glycoforms induce production of autoantibodies that subsequently bind hinge-region of galactose-deficient IgA1 molecules, resulting in the formation of nephritogenic immune complexes. Some of these complexes deposit in the kidney, activate mesangial cells, and incite glomerular injury. Thus, galactose-deficient IgA1 is central to the disease process. In this article, we review studies concerning IgA1 O-glycosylation that have contributed to the current understanding of the role of IgA1 in the pathogenesis of IgA nephropathy.

| S-EPMC7170174 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data