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Scandinavian Journal of Immunology Feb 2021Inflammation can be created by several different causes, including a blood clot, an immune system disorder, a cancer, an infection, a chemical exposure, a physical... (Review)
Review
Inflammation can be created by several different causes, including a blood clot, an immune system disorder, a cancer, an infection, a chemical exposure, a physical injury, or a neurological condition, such as Alzheimer's or depression. In particular, many infections by viral, bacterial, fungal and protozoan pathogens can cause inflammation. Inflammations can have far-reaching medical consequences, because chronic or frequent inflammation can assist cancers and initiate autoimmune diseases. Determining the cause of an inflammation can be essential for the medical treatment of an individual, and a classification system can be a useful tool to help a diagnosis, confirm a diagnosis and to determine the most appropriate treatment. However, at present there is no classification system for the different causes of inflammation. This paper describes a classification system that uses seven distinct cytokine parameters to enable the determination of the cause of an inflammation. This classification system is expandable, and it can help determine whether an inflammation is caused by an ischaemia, an immune system disorder, a cancer, an infection, a chemical, a physical injury, or a neurological condition. In some cases, this classification system can help enable a quick primary or secondary determination of an urgent medical emergency when other medical diagnostic resources are unavailable.
Topics: Autoimmune Diseases; Cytokines; Humans; Immune System; Inflammation
PubMed: 32892387
DOI: 10.1111/sji.12970 -
Multiple Sclerosis (Houndmills,... Oct 2019Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare autoimmune disorder with antibodies against the MOG predominantly involving the optic nerve and... (Review)
Review
Myelin oligodendrocyte glycoprotein (MOG) antibody disease is a rare autoimmune disorder with antibodies against the MOG predominantly involving the optic nerve and spinal cord leading to vision loss and paralysis. When MOG antibody disease involves the brain, the phenotype is similar to acute disseminated encephalomyelitis (ADEM). In this review, we discuss MOG-positive cases presenting with encephalitis, encephalopathy, or ADEM-like presentation based on recently published series.
Topics: Adrenal Cortex Hormones; Autoantibodies; Demyelinating Autoimmune Diseases, CNS; Disease Progression; Encephalitis; Encephalomyelitis; Humans; Immunoglobulins, Intravenous; Immunologic Factors; Immunosuppressive Agents; Magnetic Resonance Imaging; Myelin-Oligodendrocyte Glycoprotein; Optic Neuritis; Plasma Exchange
PubMed: 30907249
DOI: 10.1177/1352458519837705 -
Annali Dell'Istituto Superiore Di Sanita 2016Autoimmune diseases are characterized by an exaggerated immune response leading to damage and dysfunction of specific or multiple organs and tissues. Most autoimmune... (Review)
Review
Autoimmune diseases are characterized by an exaggerated immune response leading to damage and dysfunction of specific or multiple organs and tissues. Most autoimmune diseases are more prevalent in women than in men. Symptom severity, disease course, response to therapy and overall survival may also differ between males and females with autoimmune diseases. Sex hormones have a crucial role in this sex bias, with estrogens being potent stimulators of autoimmunity and androgens playing a protective role. Accumulating evidence indicates that genetic, epigenetic and environmental factors may also contribute to sex-related differences in risk and clinical course of autoimmune diseases. In this review, we discuss possible mechanisms for sex specific differences in autoimmunity with a special focus on three paradigmatic diseases: systemic lupus erythematosus, rheumatoid arthritis, and multiple sclerosis.
Topics: Autoimmune Diseases; Female; Gonadal Steroid Hormones; Humans; Male; Microbiota; Sex Characteristics; Sex Factors
PubMed: 27364395
DOI: 10.4415/ANN_16_02_12 -
Frontiers in Immunology 2023Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is... (Review)
Review
Myasthenia gravis (MG) is a neuromuscular autoimmune disorder characterized by chronic but intermittent fatigue of the eye- and general body muscles. Muscle weakness is caused primarily by the binding of an autoantibody to the acetylcholine receptors, resulting in blockage of normal neuromuscular signal transmission. Studies revealed substantial contributions of different proinflammatory or inflammatory mediators in the pathogenesis of MG. Despite these findings, compared to therapeutic approaches that target autoantibody and complements, only a few therapeutics against key inflammatory molecules have been designed or tested in MG clinical trials. Recent research focuses largely on identifying unknown molecular pathways and novel targets involved in inflammation associated with MG. A well-designed combination or adjunct treatment utilizing one or more selective and validated promising biomarkers of inflammation as a component of targeted therapy may yield better treatment outcomes. This review briefly discusses some preclinical and clinical findings of inflammation associated with MG and current therapy approaches and suggest the potential of targeting important inflammatory marker(s) along with current monoclonal antibody or antibody fragment based targeted therapies directed to a variety of cell surface receptors.
Topics: Humans; Myasthenia Gravis; Receptors, Cholinergic; Autoantibodies; Muscles; Inflammation
PubMed: 36793733
DOI: 10.3389/fimmu.2023.1110499 -
Blood Nov 2016Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid... (Review)
Review
Pure red cell aplasia (PRCA) is a syndrome defined by a normocytic normochromic anemia with severe reticulocytopenia and marked reduction or absence of erythroid precursors from the bone marrow. Diamond-Blackfan anemia is a congenital form of PRCA. Acquired PRCA may be either a primary disorder or secondary to some other disorder or agent. Primary acquired PRCA is an autoimmune disorder that is frequently antibody-mediated. Myelodysplastic syndromes may also present with the morphologic appearance of PRCA. Secondary acquired PRCA may be associated with collagen vascular/autoimmune disorders such as systemic lupus erythematosus; lymphoproliferative disorders such as chronic lymphocytic leukemia or large granular lymphocyte leukemia; infections, particularly B19 parvovirus; thymoma and other solid tumors; or a variety of other disorders, drugs, or toxic agents. The therapeutic approach to PRCA typically involves immunosuppression, but specific pathogenic subtypes are associated with specific therapeutic approaches. Cyclosporine A, with or without concurrent corticosteroids, appears to be the single most effective immunosuppressive agent.
Topics: Anemia, Diamond-Blackfan; Autoimmune Diseases; Erythema Infectiosum; Humans; Leukemia, Large Granular Lymphocytic; Leukemia, Lymphocytic, Chronic, B-Cell; Lupus Erythematosus, Systemic; Myelodysplastic Syndromes; Parvovirus B19, Human
PubMed: 27881371
DOI: 10.1182/blood-2016-05-717140 -
British Journal of Haematology Aug 2017Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 /l, is a common medical problem for children and adults. There are many causes for neutropenia,... (Review)
Review
Neutropenia, usually defined as a blood neutrophil count <1·5 × 10 /l, is a common medical problem for children and adults. There are many causes for neutropenia, and at each stage in life the clinical pattern of causes and consequences differs significantly. I recommend utilizing the age of the child and clinical observations for the preliminary diagnosis and primary management. In premature infants, neutropenia is quite common and contributes to the risk of sepsis with necrotizing enterocolitis. At birth and for the first few months of life, neutropenia is often attributable to isoimmune or alloimmune mechanisms and predisposes to the risk of severe bacterial infections. Thereafter when a child is discovered to have neutropenia, often associated with relatively minor symptoms, it is usually attributed to autoimmune disorder or viral infection. The congenital neutropenia syndromes are usually recognized when there are recurrent infections, the neutropenia is severe and there are congenital anomalies suggesting a genetic disorder. This review focuses on the key clinical finding and laboratory tests for diagnosis with commentaries on treatment, particularly the use of granulocyte colony-stimulating factor to treat childhood neutropenia.
Topics: Autoimmune Diseases; Child; Granulocyte Colony-Stimulating Factor; Humans; Infant; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neutropenia
PubMed: 28419427
DOI: 10.1111/bjh.14677 -
Frontiers in Immunology 2019Historically, systemic self-inflammatory conditions were classified as either autoinflammatory and caused by the innate immune system or autoimmune and driven by... (Review)
Review
Historically, systemic self-inflammatory conditions were classified as either autoinflammatory and caused by the innate immune system or autoimmune and driven by adaptive immune responses. However, it became clear that reality is much more complex and that autoimmune/inflammatory conditions range along an "inflammatory spectrum" with primarily autoinflammatory vs. autoimmune conditions resembling extremes at either end. Epigenetic modifications influence gene expression and alter cellular functions without modifying the genomic sequence. Methylation of CpG DNA dinucleotides and/or their hydroxymethylation, post-translational modifications to amino termini of histone proteins, and non-coding RNA expression are main epigenetic events. The pathophysiology of autoimmune/inflammatory diseases has been closely linked with disease causing gene mutations (rare) or a combination of genetic susceptibility and epigenetic modifications arising from exposure to the environment (more common). Over recent years, progress has been made in understanding molecular mechanisms involved in systemic inflammation and the contribution of innate and adaptive immune responses. Epigenetic events have been identified as (i) central pathophysiological factors in addition to genetic disease predisposition and (ii) as co-factors determining clinical pictures and outcomes in individuals with monogenic disease. Thus, a complete understanding of epigenetic contributors to autoimmune/inflammatory disease will result in approaches to predict individual disease outcomes and the introduction of effective, target-directed, and tolerable therapies. Here, we summarize recent findings that signify the importance of epigenetic modifications in autoimmune/inflammatory disorders along the inflammatory spectrum choosing three examples: the autoinflammatory bone condition chronic nonbacterial osteomyelitis (CNO), the "mixed pattern" disorder psoriasis, and the autoimmune disease systemic lupus erythematosus (SLE).
Topics: Autoimmune Diseases; CpG Islands; DNA Methylation; Epigenesis, Genetic; Epigenomics; Humans; Inflammation; Protein Processing, Post-Translational
PubMed: 31333659
DOI: 10.3389/fimmu.2019.01525 -
International Journal of Molecular... Jan 2021Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most... (Review)
Review
Chronic tic disorder and Tourette syndrome are common childhood-onset neurological diseases. However, the pathophysiology underlying these disorders is unclear, and most studies have focused on the disinhibition of the corticostriatal-thalamocortical circuit. An autoimmune dysfunction has been proposed in the pathogenetic mechanism of Tourette syndrome and related neuropsychiatric disorders such as obsessive-compulsive disorder, autism, and attention-deficit/hyperactivity disorder. This is based on evidence from animal model studies and clinical findings. Herein, we review and give an update on the clinical characteristics, clinical evidence, and genetic studies in vitro as well as animal studies regarding immune dysfunction in Tourette syndrome.
Topics: Animals; Autoimmune Diseases; Humans; Lymphocytes; Microglia; Neurons; Obsessive-Compulsive Disorder; Streptococcal Infections; Tourette Syndrome
PubMed: 33467014
DOI: 10.3390/ijms22020853 -
Frontiers in Immunology 2020Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a... (Review)
Review
Autoimmune hemolytic anemias mediated by cold agglutinins can be divided into cold agglutinin disease (CAD), which is a well-defined clinicopathologic entity and a clonal lymphoproliferative disorder, and secondary cold agglutinin syndrome (CAS), in which a similar picture of cold-hemolytic anemia occurs secondary to another distinct clinical disease. Thus, the pathogenesis in CAD is quite different from that of polyclonal autoimmune diseases such as warm-antibody AIHA. In both CAD and CAS, hemolysis is mediated by the classical complement pathway and therefore can result in generation of anaphylotoxins, such as complement split product 3a (C3a) and, to some extent, C5a. On the other hand, infection and inflammation can act as triggers and drivers of hemolysis, exemplified by exacerbation of CAD in situations with acute phase reaction and the role of specific infections (particularly and Epstein-Barr virus) as causes of CAS. In this review, the putative mechanisms behind these phenomena will be explained along with other recent achievements in the understanding of pathogenesis in these disorders. Therapeutic approaches have been directed against the clonal lymphoproliferation in CAD or the underlying disease in CAS. Currently, novel targeted treatments, in particular complement-directed therapies, are also being rapidly developed and will be reviewed.
Topics: Anemia, Hemolytic, Autoimmune; Cryoglobulins; Hemolysis; Humans
PubMed: 32318071
DOI: 10.3389/fimmu.2020.00590 -
Human Reproduction Update Jul 2019Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Endometriosis is a chronic gynaecological disorder that affects 2-10% of women of reproductive age. The aetiology of endometriosis is largely under-explored, yet abnormalities in the immune system have been suggested to explain the origin of ectopic endometrial tissues, and an association between endometriosis and autoimmune diseases has been proposed. Evaluation of current evidence investigating the association between endometriosis and autoimmune diseases from population-based studies will facilitate our understanding of the causes and consequences of endometriosis and provide a reference for better healthcare practices population-wide.
OBJECTIVE AND RATIONALE
The aim of this study was to systematically review the literature on population-based studies investigating an association between endometriosis and autoimmune diseases and to conduct a meta-analysis of combinable results to investigate the extent and robustness of evidence.
SEARCH METHODS
Four electronic databases were searched (MEDLINE, Embase, Web of Science, and CINAHL) from each database inception date until 7 April 2018. Search terms included a combination of database-specific controlled vocabulary terms and free-text terms relating to 'endometriosis' and 'autoimmune diseases'. Study inclusion criteria focused on peer-reviewed published articles that reported an association between endometriosis and autoimmune diseases, excluding case reports/series, review papers, meta-analyses, organizational guidelines, editorial letters, expert opinions, and conference abstracts. Quality assessment of included studies was performed based on GRADE criteria. Key information of eligible studies was abstracted into a standard form. Meta-analysis was performed for autoimmune diseases with combinable study results from at least three studies investigating an association with endometriosis. For cross-sectional studies and case-control studies, raw data from each study were documented to calculate a Mantel-Haenszel odds ratio with 95% CIs. For cohort studies, an inverse variance probability weighted model was used to pool study results to calculate a rate ratio (a hazard ratio or a standardized incidence rate) with 95% CIs.
OUTCOMES
A total of 26 published population-based cross-sectional, case-control, and cohort studies that investigated the association between endometriosis and autoimmune diseases met all eligible criteria and were included in the review. The studies quantified an association between endometriosis and several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjögren's syndrome (SS), rheumatoid arthritis (RA), autoimmune thyroid disorder, coeliac disease (CLD), multiple sclerosis (MS), inflammatory bowel disease (IBD), and Addison's disease. However, the quality of the evidence was generally poor due to the high risk of bias in the majority of the chosen study designs and statistical analyses. Only 5 of the 26 studies could provide high-quality evidence, and among these, 4 supported a statistically significant association between endometriosis and at least 1 autoimmune disease: SLE, SS, RA, CLD, MS, or IBD.
WIDER IMPLICATIONS
The observed associations between endometriosis and autoimmune diseases suggest that clinicians need to be aware of the potential coexistence of endometriosis and autoimmune diseases when either is diagnosed. Scientists interested in research studies on endometriosis or autoimmune diseases should consider the likelihood of comorbidity when studying these two types of health conditions. Well-designed large prospective cohort studies with confounding control and mediation quantification, as well as genetic and biological studies, are needed to generate further insights into whether endometriosis is a risk factor for, or a consequence of, autoimmune diseases, and whether these two types of disorders share pathophysiological mechanisms even if they arise independently. Such insights may offer opportunities for the development of novel non-hormonal medications such as immuno-modulators or repurposing of existing immunomodulatory therapies for endometriosis.
Topics: Autoimmune Diseases; Case-Control Studies; Cohort Studies; Cross-Sectional Studies; Endometriosis; Female; Humans; Prospective Studies; Risk Factors; Sjogren's Syndrome
PubMed: 31260048
DOI: 10.1093/humupd/dmz014