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Phagocytosis in the Brain: Homeostasis and Disease
Conclusions and Perspectives In this review we have summarized the critical role phagocytosis plays in both CNS homeostasis and disease. While much progress has been made in recent years, many unanswered questions remain. How phagocytosis in the CNS is influenced by numerous factors, such as microenvironment or phagocytic target, have yet to be fully resolved. Additionally, the utilization of novel technologies, including in vivo imaging techniques (217), iPSC-derived microglia (213) and high-throughput screens (66), will likely contribute to further identification of phagocytic pathways and consequences of phagocytosis w...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Blood Cell-Bound C4d as a Marker of Complement Activation in Patients With the Antiphospholipid Syndrome
In conclusion the detection of complement activation products on circulating erythrocytes and platelets using a highly sensitive and specific assay further supports the view that APS is a complement-mediated disorder. Increased EC4d and PC4d percentages are associated with the active inflammatory disease in SLE. It is difficult to translate this finding to APS which is a non-acute inflammatory disorder. We failed to find an association with both the classification and non-classification criteria, including thrombocytopenia. However, we believe that this sensitive tool to evaluate complement activation may offer more inform...
Source: Frontiers in Immunology - April 11, 2019 Category: Allergy & Immunology Source Type: research

New Biomarkers for Atherothrombosis in Antiphospholipid Syndrome: Genomics and Epigenetics Approaches
Conclusions In recent years, there have been many advances in the understanding of the molecular basis for vascular involvement in APS, but many areas need to be further investigated, in particular the association between altered genetic/epigenetic profiles, autoantibodies and clinical manifestations, and the effectiveness of new therapeutic strategies. It would be interesting to apply next generation sequencing technologies like RNA-Seq along with GWAS to screen both, the gene profile and the whole transcriptome of large cohorts of primary APS patients, in order to reveal the mutations/polymorphisms, post-transcriptiona...
Source: Frontiers in Immunology - April 15, 2019 Category: Allergy & Immunology Source Type: research

Subclinical Atherosclerosis in Primary Sj ögren's Syndrome: Does Inflammation Matter?
Conclusions The markers of endothelial activation and damage and of chronic inflammation investigated until now failed to result predictors of subclinical atherosclerosis or to be associated with increased risk of CV events in SS patients. This may suggest that other mechanisms are implicated with increased prevalence of subclinical atherosclerosis in SS or that these biomarkers exert a different mechanism in the pathogenesis of endothelial damage and in the induction of atherosclerosis. Surely, the relationship between the disease itself and inflammatory and immune dysfunction factors is quite complex and still to be cla...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Pentraxin 3 in Cardiovascular Disease
Giuseppe Ristagno1*, Francesca Fumagalli1, Barbara Bottazzi2, Alberto Mantovani2,3,4, Davide Olivari1, Deborah Novelli1 and Roberto Latini1 1Department of Cardiovascular Research, Mario Negri Institute for Pharmacological Research IRCCS, Milan, Italy 2Humanitas Clinical and Research Center-IRCCS, Milan, Italy 3Humanitas University, Milan, Italy 4The William Harvey Research Institute, Queen Mary University of London, London, United Kingdom The long pentraxin PTX3 is a member of the pentraxin family produced locally by stromal and myeloid cells in response to proinflammatory signals and microbial moieties. The p...
Source: Frontiers in Immunology - April 16, 2019 Category: Allergy & Immunology Source Type: research

Notch Signaling Regulates Immune Responses in Atherosclerosis
Atherosclerosis is a chronic autoimmune inflammatory disease that can cause coronary artery disease, stroke, peripheral artery disease, depending on which arteries are affected. At the beginning of atherosclerosis plasma lipoproteins accumulate in the sub-endothelial space. In response, monocytes migrate from the circulation through the endothelium into the intima where they differentiate into macrophages. These early events trigger a complex immune response that eventually involves many cellular subtypes of both innate and adaptive immunity. The Notch signaling pathway is an evolutionary conserved cell signaling system th...
Source: Frontiers in Immunology - May 22, 2019 Category: Allergy & Immunology Source Type: research

A Case of Multiple Sclerosis —Like Relapsing Remitting Encephalomyelitis Following Allogeneic Hematopoietic Stem Cell Transplantation and a Review of the Published Literature
Complications involving the central nervous system (CNS) occur in 9–14% of patients following allogeneic hematopoietic stem cell transplantation (HSCT), including stroke-like episodes, demyelination, encephalitis, and nonspecific neurological symptoms. Here we report a case of multiple sclerosis (MS) like relapsing remitting encephalomyelitis following allogeneic HSCT, which did not respond to disease modifying therapies (DMTs) and “domino” autologous HSCT. A 53-year-old male was treated with allogeneic HSCT for lymphoid blast transformation of chronic myeloid leukemia. Ten months later he presented with confusion, s...
Source: Frontiers in Immunology - May 4, 2020 Category: Allergy & Immunology Source Type: research

Case Report: Signal Transducer and Activator of Transcription 3 Gain-of-Function and Spectrin Deficiency: A Life-Threatening Case of Severe Hemolytic Anemia
STAT3 gain-of-function (GOF) mutations can be responsible for an incomplete phenotype mainly characterized by hematological autoimmunity, even in the absence of other organ autoimmunity, growth impairment, or severe infections. We hereby report a case with an incomplete form of STAT3 GOF intensified by a concomitant hereditary hematological disease, which misleads the diagnosis. The patient presented with lymphadenopathy, splenomegaly, hypogammaglobulinemia, and severe autoimmune hemolytic anemia (AIHA) with critical complications, including stroke. A Primary Immune Regulatory Disorders (PIRD) was suspected, and molecular ...
Source: Frontiers in Immunology - January 15, 2021 Category: Allergy & Immunology Source Type: research

Deficiency of Human Adenosine Deaminase Type 2 – A Diagnostic Conundrum for the Hematologist
Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Patients with DADA2 can have variable patterns of cytopenias and bone marrow failure syndromes. Patients with DADA2 who have predominant haematological manifestations are associated with ADA2 gene variants that result i...
Source: Frontiers in Immunology - May 3, 2022 Category: Allergy & Immunology Source Type: research

TREGking From Gut to Brain: The Control of Regulatory T Cells Along the Gut-Brain Axis
The human gastrointestinal tract has an enormous and diverse microbial community, termed microbiota, that is necessary for the development of the immune system and tissue homeostasis. In contrast, microbial dysbiosis is associated with various inflammatory and autoimmune diseases as well as neurological disorders in humans by affecting not only the immune system in the gastrointestinal tract but also other distal organs. FOXP3+ regulatory T cells (Tregs) are a subset of CD4+ helper T cell lineages that function as a gatekeeper for immune activation and are essential for peripheral autoimmunity prevention. Tregs are crucial...
Source: Frontiers in Immunology - June 30, 2022 Category: Allergy & Immunology Source Type: research