Beyond GWAS: from simple associations to functional insights
AbstractEach human, when born, has slightly different DNA sequences, which make each of us unique. The variations in DNA sequences are called genetic variants. The primary aim of genome-wide association study (GWAS) is to detect associations between genetic variants and human phenotypes. Since GWAS focuses on germ-line variants, there is no reverse causation. Therefore, GWAS is one of the few tools that can assess the causality of human diseases. In the past 10 years, many large-scale GWAS have been conducted. Although the primary outputs of GWAS are just a series of statistics, its downstream analyses provided many insi...
Source: Seminars in Immunopathology - October 4, 2021 Category: Pathology Source Type: research
How will artificial intelligence and bioinformatics change our understanding of IgA Nephropathy in the next decade?
AbstractIgA nephropathy (IgAN) is the most common glomerulonephritis. It is characterized by the deposition of immune complexes containing immunoglobulin A (IgA) in the kidney ’s glomeruli, triggering an inflammatory process. In many patients, the disease has a progressive course, eventually leading to end-stage kidney disease. The current understanding of IgAN’s pathophysiology is incomplete, with the involvement of several potential players, including the mucosal im mune system, the complement system, and the microbiome. Dissecting this complex pathophysiology requires an integrated analysis across molecular, cellula...
Source: Seminars in Immunopathology - October 1, 2021 Category: Pathology Source Type: research
IgA nephropathy: a perspective for 2021
(Source: Seminars in Immunopathology)
Source: Seminars in Immunopathology - October 1, 2021 Category: Pathology Source Type: research
Correction to: How will artificial intelligence and bioinformatics change our understanding of IgA Nephropathy in the next decade?
A Correction to this paper has been published: 10.1007/s00281-021-00858-9 (Source: Seminars in Immunopathology)
Source: Seminars in Immunopathology - October 1, 2021 Category: Pathology Source Type: research
IgA nephropathy: a perspective for 2021
(Source: Seminars in Immunopathology)
Source: Seminars in Immunopathology - October 1, 2021 Category: Pathology Source Type: research
Genetic overlap between type 1 diabetes and other autoimmune diseases
AbstractType 1 diabetes (T1D) is a chronic disease caused by the destruction of pancreatic β cells, which is driven by autoreactive T lymphocytes. It has been described that a high proportion of T1D patients develop other autoimmune diseases (AIDs), such as autoimmune thyroid disease, celiac disease, or vitiligo, which suggests the existence of common etiological factors among these diso rders. In this regard, genetic studies have identified a high number ofloci consistently associated with T1D that also represent established genetic risk factors for other AIDs. In addition, studies focused on identifying the shared genet...
Source: Seminars in Immunopathology - October 1, 2021 Category: Pathology Source Type: research
Glucocorticoid circadian rhythms in immune function
AbstractAdrenal glucocorticoid (GC) hormones are important regulators of energy metabolism, brain functions, and the immune system. Their release follows robust diurnal rhythms and GCs themselves serve as entrainment signals for circadian clocks in various tissues. In the clinics, synthetic GC analogues are widely used as immunosuppressive drugs. GC inhibitory effects on the immune system are well documented and include suppression of cytokines and increased immune cell death. However, the circadian dynamics of GC action are often neglected. Synthetic GC medications fail to mimic complex GC natural rhythms. Several recent ...
Source: Seminars in Immunopathology - September 28, 2021 Category: Pathology Source Type: research
IgA glycosylation and immune complex formation in IgAN
AbstractIgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. This disease, discovered in 1968, is characterized by IgA-IgG glomerular immunodeposits with a mesangial pattern. It is thought that these immunodeposits originate from the immune complexes formed in the circulation. It is hypothesized that the pathogenesis of IgAN is driven by aberrant glycoforms of IgA1 (galactose-deficient IgA1, Gd-IgA1). Gd-IgA1, in genetically susceptible individuals, represents the initiating factor for the formation of circulating immune complexes due to its recognition by IgG autoantibodies and the subsequent fo...
Source: Seminars in Immunopathology - September 27, 2021 Category: Pathology Source Type: research
Functional interrogation of autoimmune disease genetics using CRISPR/Cas9 technologies and massively parallel reporter assays
AbstractGenetic studies, including genome-wide association studies, have identified many common variants that are associated with autoimmune diseases. Strikingly, in addition to being frequently observed in healthy individuals, a number of these variants are shared across diseases with diverse clinical presentations. This highlights the potential for improved autoimmune disease understanding which could be achieved by characterising the mechanism by which variants lead to increased risk of disease. Of particular interest is the potential for identifying novel drug targets or of repositioning drugs currently used in other d...
Source: Seminars in Immunopathology - September 10, 2021 Category: Pathology Source Type: research
