Current treatment of IgA nephropathy
AbstractIgA nephropathy (IgAN) is the most common type of glomerulonephritis in Asia and the Western world. In most patients, it follows an asymptomatic to oligosymptomatic course and GFR loss, if any, is slow. The mainstay of therapy therefore is optimized supportive care, i.e., measures that lower blood pressure, reduce proteinuria, minimize lifestyle risk factors, and otherwise help to reduce non-specific insults to the kidneys. The value of immunosuppression has become controversial and if at all, systemic high-dose corticosteroid therapy should be considered for a few months taking into account patient characteristics...
Source: Seminars in Immunopathology - September 8, 2021 Category: Pathology Source Type: research
Cap analysis of gene expression (CAGE) and noncoding regulatory elements
AbstractCap analysis of gene expression (CAGE) was developed to detect the 5 ′ end of RNA. Trapping of the RNA 5′-cap structure enables the enrichment and selective sequencing of complete transcripts. Upscaled high-throughput versions of CAGE have enabled the genome-wide identification of transcription start sites, including transcriptionally active promoters and enhance rs. CAGE sequencing can be exploited to draw comprehensive maps of active genomic regulatory elements in a cell type- and activation-specific manner. The cells of the immune system are among the best candidates to be analyzed in humans, since they are ...
Source: Seminars in Immunopathology - September 1, 2021 Category: Pathology Source Type: research
Functional heterogeneity of CD4+ T cells in liver inflammation
AbstractCD4+ T cells play an essential role in orchestrating adequate immunity, but their overactivity has been associated with the development of immune-mediated inflammatory diseases, including liver inflammatory diseases. These cells can be subclassified according to their maturation stage, cytokine profile, and pro or anti-inflammatory functions, i.e., functional heterogeneity. In this review, we summarize what has been discovered so far regarding the role of the different CD4+ T cell polarization states in the progression of two prominent and still different liver inflammatory diseases: non-alcoholic steatohepatitis (...
Source: Seminars in Immunopathology - August 31, 2021 Category: Pathology Source Type: research
Is IgA nephropathy the same disease in different parts of the world?
AbstractSince it was first described in 1968, immunoglobulin A nephropathy (IgAN) is understood to be the most common form of glomerulonephritis worldwide. The diagnosis of IgAN depends on the presence of dominant mesangial IgA1 deposition by renal biopsy. To date, a wide spectrum of clinical and pathologic features of IgAN have been observed, implying that IgAN might not be the same disease across the world. Here, we review the characteristics of IgAN from perspectives of epidemiology, clinical-pathological patterns, disease pathogenesis, and treatment response across different ethnic populations. Overall, IgAN is most pr...
Source: Seminars in Immunopathology - August 20, 2021 Category: Pathology Source Type: research
Complement activation in IgA nephropathy
AbstractIgA nephropathy pathogenesis is incompletely understood, and this limits the development of disease-specific biomarkers and effective therapies. Evidence of complement activity in IgA nephropathy is well established. However, a growing body of research indicates complement activity is an important contributor to IgA nephropathy pathology. In particular, multiple associations have been identified between complement alternative, lectin and terminal pathway proteins and IgA nephropathy severity. Recently, we have also gained insight into possible mechanisms that could link glomerular IgA deposition, complement activit...
Source: Seminars in Immunopathology - August 11, 2021 Category: Pathology Source Type: research
The immune landscape of IgA induction in the gut
AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of micr...
Source: Seminars in Immunopathology - August 11, 2021 Category: Pathology Source Type: research
Complement activation in IgA nephropathy
AbstractIgA nephropathy pathogenesis is incompletely understood, and this limits the development of disease-specific biomarkers and effective therapies. Evidence of complement activity in IgA nephropathy is well established. However, a growing body of research indicates complement activity is an important contributor to IgA nephropathy pathology. In particular, multiple associations have been identified between complement alternative, lectin and terminal pathway proteins and IgA nephropathy severity. Recently, we have also gained insight into possible mechanisms that could link glomerular IgA deposition, complement activit...
Source: Seminars in Immunopathology - August 11, 2021 Category: Pathology Source Type: research
The immune landscape of IgA induction in the gut
AbstractAntibodies are key elements of protective immunity. In the mucosal immune system in particular, secretory immunoglobulin A (SIgA), the most abundantly produced antibody isotype, protects against infections, shields the mucosal surface from toxins and environmental factors, and regulates immune homeostasis and a peaceful coexistence with our microbiota. However, the dark side of IgA biology promotes the formation of immune complexes and provokes pathologies, e.g., IgA nephropathy (IgAN). The precise mechanisms of how IgA responses become deregulated and pathogenic in IgAN remain unresolved. Yet, as the field of micr...
Source: Seminars in Immunopathology - August 11, 2021 Category: Pathology Source Type: research
Monocyte dysregulation: consequences for hepatic infections
AbstractLiver disorders due to infections are a substantial health concern in underdeveloped and industrialized countries. This includes not only hepatotropic viruses (e.g., hepatitis B, hepatitis C) but also bacterial and parasitic infections such as amebiasis, leishmaniasis, schistosomiasis, or echinococcosis. Recent studies of the immune mechanisms underlying liver disease show that monocytes play an essential role in determining patient outcomes. Monocytes are derived from the mononuclear phagocyte lineage in the bone marrow and are present in nearly all tissues of the body; these cells function as part of the early in...
Source: Seminars in Immunopathology - August 1, 2021 Category: Pathology Source Type: research
The good and the bad about separation anxiety: roles of IL-22 and IL-22BP in liver pathologies
AbstractThe human liver fulfills several vital tasks daily and possesses an impressive ability to self-regenerate. However, the capacity of this self-healing process can be exhausted by a variety of different liver diseases, such as alcoholic liver damage, viral hepatitis, or hepatocellular carcinoma. Over time, all these diseases generally lead to progressive liver failure that can become fatal if left untreated. Thus, a great effort has been directed towards the development of innovative therapies. The most recently discovered therapies often involve modifying the patient ’s immune system to enhance a beneficial immune...
Source: Seminars in Immunopathology - August 1, 2021 Category: Pathology Source Type: research
The two facets of gp130 signalling in liver tumorigenesis
AbstractThe liver is a vital organ with multiple functions and a large regenerative capacity. Tumours of the liver are the second most frequently cause of cancer-related death and develop in chronically inflamed livers. IL-6-type cytokines are mediators of inflammation and almost all members signal via the receptor subunit gp130 and the downstream signalling molecule STAT3. We here summarize current knowledge on how gp130 signalling and STAT3 in tumour cells and cells of the tumour micro-environment drives hepatic tumorigenesis. We furthermore discuss very recent findings describing also anti-tumorigenic roles of gp130/STA...
Source: Seminars in Immunopathology - August 1, 2021 Category: Pathology Source Type: research
