Age as a risk factor in vasculitis
AbstractTwo vasculitides, giant cell arteritis (GCA) and Takayasu arteritis (TAK), are recognized as autoimmune and autoinflammatory diseases that manifest exclusively within the aorta and its large branches. In both entities, the age of the affected host is a critical risk factor. TAK manifests during the 2nd –4th decade of life, occurring while the immune system is at its height of performance. GCA is a disease of older individuals, with infrequent cases during the 6th decade and peak incidence during the 8th decade of life. In both vasculitides, macrophages and T cells infiltrate into the adventitia and media of affec...
Source: Seminars in Immunopathology - February 9, 2022 Category: Pathology Source Type: research
Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome
AbstractAntiphospholipid syndrome (APS) is an autoimmune thrombophilia propelled by circulating antiphospholipid antibodies that herald vascular thrombosis and obstetrical complications. Antiphospholipid antibodies recognize phospholipids and phospholipid-binding proteins and are not only markers of disease but also key drivers of APS pathophysiology. Thrombotic events in APS can be attributed to various conspirators including activated endothelial cells, platelets, and myeloid-lineage cells, as well as derangements in coagulation and fibrinolytic systems. Furthermore, recent work has especially highlighted the role of neu...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
Clonal hematopoiesis and vascular disease
AbstractSomatic mutations in hematopoietic stem cells are common with aging and can result in expansion of clones harboring mutations, termed clonal hematopoiesis. This results in an increased risk of blood cancers but has also been linked with chronic inflammatory disease states. In recent years, clonal hematopoiesis has been established to have a causative role in atherogenesis and cardiovascular disease. Additionally, as the effector cells have been identified to be immune cells, there is ongoing interest in assessing whether dysregulated immune function plays a role in other chronic inflammatory conditions such as rheu...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
TNF in the liver: targeting a central player in inflammation
AbstractTumour necrosis factor- α (TNF) is a multifunctional cytokine. First recognized as an endogenous soluble factor that induces necrosis of solid tumours, TNF became increasingly important as pro-inflammatory cytokine being involved in the immunopathogenesis of several autoimmune diseases. In the liver, TNF induces numerous biological responses such as hepatocyte apoptosis and necroptosis, liver inflammation and regeneration, and autoimmunity, but also progression to hepatocellular carcinoma. Considering these multiple functions of TNF in the liver, we propose anti-TNF therapies that specifically target TNF signallin...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
Mechanisms of immunothrombosis and vasculopathy in antiphospholipid syndrome
AbstractAntiphospholipid syndrome (APS) is an autoimmune thrombophilia propelled by circulating antiphospholipid antibodies that herald vascular thrombosis and obstetrical complications. Antiphospholipid antibodies recognize phospholipids and phospholipid-binding proteins and are not only markers of disease but also key drivers of APS pathophysiology. Thrombotic events in APS can be attributed to various conspirators including activated endothelial cells, platelets, and myeloid-lineage cells, as well as derangements in coagulation and fibrinolytic systems. Furthermore, recent work has especially highlighted the role of neu...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
Clonal hematopoiesis and vascular disease
AbstractSomatic mutations in hematopoietic stem cells are common with aging and can result in expansion of clones harboring mutations, termed clonal hematopoiesis. This results in an increased risk of blood cancers but has also been linked with chronic inflammatory disease states. In recent years, clonal hematopoiesis has been established to have a causative role in atherogenesis and cardiovascular disease. Additionally, as the effector cells have been identified to be immune cells, there is ongoing interest in assessing whether dysregulated immune function plays a role in other chronic inflammatory conditions such as rheu...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
TNF in the liver: targeting a central player in inflammation
AbstractTumour necrosis factor- α (TNF) is a multifunctional cytokine. First recognized as an endogenous soluble factor that induces necrosis of solid tumours, TNF became increasingly important as pro-inflammatory cytokine being involved in the immunopathogenesis of several autoimmune diseases. In the liver, TNF induces numerous biological responses such as hepatocyte apoptosis and necroptosis, liver inflammation and regeneration, and autoimmunity, but also progression to hepatocellular carcinoma. Considering these multiple functions of TNF in the liver, we propose anti-TNF therapies that specifically target TNF signallin...
Source: Seminars in Immunopathology - February 4, 2022 Category: Pathology Source Type: research
Genetics of rheumatoid arthritis
AbstractRheumatoid arthritis (RA) is an inflammatory autoimmune disease involving symmetric joints and is generally characterized by persistent pain, tenderness, and destruction of joints. The vast majority of RA patients produce autoantibodies, and immune cell involvement in disease development is well recognized, as is the contribution of other types of cells in synovial tissue, like fibroblasts. It is known that there are major genetic associations with the HLA locus, while multiple non-HLA genetic variants display relatively low risk of RA. Both HLA and non-HLA associations suggest that the profiles of genetic associat...
Source: Seminars in Immunopathology - January 27, 2022 Category: Pathology Source Type: research
Methods for statistical fine-mapping and their applications to auto-immune diseases
AbstractAlthough genome-wide association studies (GWAS) have identified thousands of loci in the human genome that are associated with different traits, understanding the biological mechanisms underlying the association signals identified in GWAS remains challenging. Statistical fine-mapping is a method aiming to refine GWAS signals by evaluating which variant(s) are truly causal to the phenotype. Here, we review the types of statistical fine-mapping methods that have been widely used to date, with a focus on recently developed functionally informed fine-mapping (FIFM) methods that utilize functional annotations. We then s...
Source: Seminars in Immunopathology - January 18, 2022 Category: Pathology Source Type: research
The contribution of sleep to the neuroendocrine regulation of rhythms in human leukocyte traffic
AbstractTwenty-four-hour rhythms in immune parameters and functions are robustly observed phenomena in biomedicine. Here, we summarize the important role of sleep and associated parameters on the neuroendocrine regulation of rhythmic immune cell traffic to different compartments, with a focus on human leukocyte subsets. Blood counts of “stress leukocytes” such as neutrophils, natural killer cells, and highly differentiated cytotoxic T cells present a rhythm with a daytime peak. It is mediated by morning increases in epinephrine, leading to a mobilization of these cells out of the marginal pool into the circulation foll...
Source: Seminars in Immunopathology - January 18, 2022 Category: Pathology Source Type: research
Methods for statistical fine-mapping and their applications to auto-immune diseases
AbstractAlthough genome-wide association studies (GWAS) have identified thousands of loci in the human genome that are associated with different traits, understanding the biological mechanisms underlying the association signals identified in GWAS remains challenging. Statistical fine-mapping is a method aiming to refine GWAS signals by evaluating which variant(s) are truly causal to the phenotype. Here, we review the types of statistical fine-mapping methods that have been widely used to date, with a focus on recently developed functionally informed fine-mapping (FIFM) methods that utilize functional annotations. We then s...
Source: Seminars in Immunopathology - January 18, 2022 Category: Pathology Source Type: research
The contribution of sleep to the neuroendocrine regulation of rhythms in human leukocyte traffic
AbstractTwenty-four-hour rhythms in immune parameters and functions are robustly observed phenomena in biomedicine. Here, we summarize the important role of sleep and associated parameters on the neuroendocrine regulation of rhythmic immune cell traffic to different compartments, with a focus on human leukocyte subsets. Blood counts of “stress leukocytes” such as neutrophils, natural killer cells, and highly differentiated cytotoxic T cells present a rhythm with a daytime peak. It is mediated by morning increases in epinephrine, leading to a mobilization of these cells out of the marginal pool into the circulation foll...
Source: Seminars in Immunopathology - January 18, 2022 Category: Pathology Source Type: research
Fine mapping with epigenetic information and 3D structure
AbstractSince 2005, thousands of genome-wide association studies (GWAS) have been published, identifying hundreds of thousands of genetic variants that increase risk of complex traits such as autoimmune diseases. This wealth of data has the potential to improve patient care, through personalized medicine and the identification of novel drug targets. However, the potential of GWAS for clinical translation has not been fully achieved yet, due to the fact that the functional interpretation of risk variants and the identification of causal variants and genes are challenging. The past decade has seen the development of great ad...
Source: Seminars in Immunopathology - January 12, 2022 Category: Pathology Source Type: research
