-
Circulation Aug 2021Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a... (Review)
Review
Myocarditis remains a clinical challenge in pediatrics. Originally, it was recognized at autopsy before the application of endomyocardial biopsy, which led to a histopathology-based diagnosis such as in the Dallas criteria. Given the invasive and low-sensitivity nature of endomyocardial biopsy, its diagnostic focus shifted to a reliance on clinical suspicion. With the advances of cardiac magnetic resonance, an examination of the whole heart in vivo has gained acceptance in the pursuit of a diagnosis of myocarditis. The presentation may vary from minimal symptoms to heart failure, life-threatening arrhythmias, or cardiogenic shock. Outcomes span full resolution to chronic heart failure and the need for heart transplantation with inadequate clues to predict the disease trajectory. The American Heart Association commissioned this writing group to explore the current knowledge and management within the field of pediatric myocarditis. This statement highlights advances in our understanding of the immunopathogenesis, new and shifting dominant pathogeneses, modern laboratory testing, and use of mechanical circulatory support, with a special emphasis on innovations in cardiac magnetic resonance imaging. Despite these strides forward, we struggle without a universally accepted definition of myocarditis, which impedes progress in disease-targeted therapy.
Topics: Animals; Biopsy; Child; Clinical Decision-Making; Combined Modality Therapy; Disease Management; Disease Models, Animal; Disease Susceptibility; Humans; Multimodal Imaging; Myocarditis; Prognosis; Symptom Assessment; Treatment Outcome
PubMed: 34229446
DOI: 10.1161/CIR.0000000000001001 -
Exercise Immunology Review 2020Multiple studies in humans and animals have demonstrated the profound impact that exercise can have on the immune system. There is a general consensus that regular bouts... (Review)
Review
Multiple studies in humans and animals have demonstrated the profound impact that exercise can have on the immune system. There is a general consensus that regular bouts of short-lasting (i.e. up to 45 minutes) moderate intensity exercise is beneficial for host immune defense, particularly in older adults and people with chronic diseases. In contrast, infection burden is reported to be high among high performance athletes and second only to injury for the number of training days lost during preparation for major sporting events. This has shaped the common view that arduous exercise (i.e. those activities practiced by high performance athletes/ military personnel that greatly exceed recommended physical activity guidelines) can suppress immunity and increase infection risk. However, the idea that exercise per se can suppress immunity and increase infection risk independently of the many other factors (e.g. anxiety, sleep disruption, travel, exposure, nutritional deficits, environmental extremes, etc.) experienced by these populations has recently been challenged. The purpose of this debate article was to solicit opposing arguments centered around this fundamental question in the exercise immunology field: can exercise affect immune function to increase susceptibility to infection. Issues that were contested between the debating groups include: (i) whether or not athletes are more susceptible to infection (mainly of the upper respiratory tract) than the general population; (ii) whether exercise per se is capable of altering immunity to increase infection risk independently of the multiple factors that activate shared immune pathways and are unique to the study populations involved; (iii) the usefulness of certain biomarkers and the interpretation of in vitro and in vivo data to monitor immune health in those who perform arduous exercise; and (iv) the quality of scientific evidence that has been used to substantiate claims for and against the potential negative effects of arduous exercise on immunity and infection risk. A key point of agreement between the groups is that infection susceptibility has a multifactorial underpinning. An issue that remains to be resolved is whether exercise per se is a causative factor of increased infection risk in athletes. This article should provide impetus for more empirical research to unravel the complex questions that surround this contentious issue in the field of exercise immunology.
Topics: Animals; Athletes; Disease Susceptibility; Exercise; Humans; Immune System; Immunity; Infections
PubMed: 32139352
DOI: No ID Found -
Blood Oct 2020Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal... (Review)
Review
Clonal expansions of mutated hematopoietic cells, termed clonal hematopoiesis, are common in aging humans. One expected consequence of mutation-associated clonal hematopoiesis is an increased risk of hematologic cancers, which has now been shown in several studies. However, the hematopoietic stem cells that acquire these somatic mutations also give rise to mutated immune effector cells, such as monocytes, granulocytes, and lymphocytes. These effector cells can potentially influence many disease states, especially those with a chronic inflammatory component. Indeed, several studies have now shown that clonal hematopoiesis associates with increased risk of atherosclerotic cardiovascular disease. Emerging data also associate clonal hematopoiesis with other nonhematologic diseases. Here, we will review recent studies linking clonal hematopoiesis to altered immune function, inflammation, and nonmalignant diseases of aging.
Topics: Animals; Biomarkers; Cardiovascular Diseases; Clonal Evolution; Clonal Hematopoiesis; Disease Susceptibility; Genetic Association Studies; Genetic Predisposition to Disease; Hematopoiesis; Humans; Mutation; Organ Specificity; Phenotype; Terminology as Topic
PubMed: 32736379
DOI: 10.1182/blood.2019000989 -
Frontiers in Immunology 2022Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the...
OBJECTIVES
Periodontitis (PD) has been linked to arthritis in previous epidemiological observational studies; however, the results are inconclusive. It remains unclear whether the association between PD and arthritis is causal. The purpose of this study was to investigate the causal association of PD with arthritis, including rheumatoid arthritis (RA) and osteoarthritis (OA).
METHODS
We performed a two-sample bidirectional Mendelian randomization (MR) analysis using publicly released genome-wide association studies (GWAS) statistics. The inverse-variance weighted (IVW) method was used as the primary analysis. We applied four complementary methods, including weighted median, weighted mode, MR-Egger regression and MR pleiotropy residual sum and outlier (MR-PRESSO) to detect and correct for the effect of horizontal pleiotropy.
RESULTS
Genetically determined PD did not have a causal effect on OA (OR = 1.06, 95% CI: 0.99-1.15, = 0.09) and RA (OR = 0.99, 95% CI: 0.87-1.13, = 0.89). Furthermore, we did not find a significant causal effect of arthritis on PD in the reverse MR analysis. The results of MR-Egger regression, Weighted Median, and Weighted Mode methods were consistent with those of the IVW method. Horizontal pleiotropy was unlikely to distort the causal estimates according to the sensitivity analysis.
CONCLUSIONS
Our MR analysis reveals non-causal association of PD with arthritis, despite observational studies reporting an association between PD and arthritis.
Topics: Arthritis; Disease Susceptibility; Genetic Predisposition to Disease; Genome-Wide Association Study; Humans; Mendelian Randomization Analysis; Periodontitis
PubMed: 35154127
DOI: 10.3389/fimmu.2022.808832 -
Immunology Jan 2022Neutrophil-centred inflammation and flawed clearance of neutrophils cause and exuberate multiple pathological conditions. These most abundant leukocytes exhibit very... (Review)
Review
Neutrophil-centred inflammation and flawed clearance of neutrophils cause and exuberate multiple pathological conditions. These most abundant leukocytes exhibit very high daily turnover in steady-state and stress conditions. Various armours including oxidative burst, NETs and proteases function against pathogens, but also dispose neutrophils to spawn pro-inflammatory responses. Neutrophils undergo death through different pathways upon ageing, infection, executing the intruder's elimination. These include non-lytic apoptosis and other lytic deaths including NETosis, necroptosis and pyroptosis with distinct disintegration of the cellular membrane. This causes release and presence of different intracellular cytotoxic, and tissue-damaging content as cell remnants in the extracellular environment. The apoptotic cells and apoptotic bodies get cleared with non-inflammatory outcomes, while lytic deaths associated remnants including histones and cell-free DNA cause pro-inflammatory responses. Indeed, the enhanced frequencies of neutrophil-associated proteases, cell-free DNA and autoantibodies in diverse pathologies including sepsis, asthma, lupus and rheumatoid arthritis, imply disturbed neutrophil resolution programmes in inflammatory and autoimmune diseases. Thus, the clearance mechanisms of neutrophils and associated remnants are vital for therapeutics. Though studies focused on clearance mechanisms of senescent or apoptotic neutrophils so far generated a good understanding of the same, clearance of neutrophils undergoing distinct lytic deaths, including NETs, are being the subjects of intense investigations. Here, in this review, we are providing the current updates in the clearance mechanisms of apoptotic neutrophils and focusing on not so well-defined recognition, uptake and degradation of neutrophils undergoing lytic death and associated remnants that may provide new therapeutic approaches in inflammation and autoimmunity.
Topics: Animals; Apoptosis; Biomarkers; Disease Susceptibility; Extracellular Traps; Gene Expression Regulation; Humans; Immunity; Inflammation; Neutrophils; Signal Transduction
PubMed: 34704249
DOI: 10.1111/imm.13423 -
Journal of Experimental & Clinical... Aug 2021Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention.... (Review)
Review
Tumor resistance to apoptosis and the immunosuppressive tumor microenvironment are two major contributors to poor therapeutic responses during cancer intervention. Pyroptosis, a lytic and inflammatory programmed cell death pathway distinct from apoptosis, has subsequently sparked notable interest among cancer researchers for its potential to be clinically harnessed and to address these problems. Recent evidence indicates that pyroptosis induction in tumor cells leads to a robust inflammatory response and marked tumor regression. Underlying its antitumor effect, pyroptosis is mediated by pore-forming gasdermin proteins that facilitate immune cell activation and infiltration through their release of pro-inflammatory cytokines and immunogenic material following cell rupture. Considering its inflammatory nature, however, aberrant pyroptosis may also be implicated in the formation of a tumor supportive microenvironment, as evidenced by the upregulation of gasdermin proteins in certain cancers. In this review, the molecular pathways leading to pyroptosis are introduced, followed by an overview of the seemingly entangled links between pyroptosis and cancer. We describe what is known regarding the impact of pyroptosis on anticancer immunity and give insight into the potential of harnessing pyroptosis as a tool and applying it to novel or existing anticancer strategies.
Topics: Animals; Biomarkers; Combined Modality Therapy; Disease Management; Disease Susceptibility; Gene Expression Regulation, Neoplastic; Humans; Immunity; Neoplasms; Pyroptosis; Signal Transduction; Treatment Outcome
PubMed: 34429144
DOI: 10.1186/s13046-021-02065-8 -
Frontiers in Immunology 2022
Topics: Humans; Antibodies, Antinuclear; Lupus Erythematosus, Systemic; Disease Susceptibility
PubMed: 36591294
DOI: 10.3389/fimmu.2022.1118180 -
International Journal of Molecular... Apr 2020Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic... (Review)
Review
Nonalcoholic fatty liver disease (NAFLD) represents a global healthcare burden since it is epidemiologically related to obesity, type 2 diabetes (T2D) and Metabolic Syndrome (MetS). It embraces a wide spectrum of hepatic injuries, which include simple steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The susceptibility to develop NAFLD is highly variable and it is influenced by several cues including environmental (i.e., dietary habits and physical activity) and inherited (i.e., genetic/epigenetic) risk factors. Nonetheless, even intestinal microbiota and its by-products play a crucial role in NAFLD pathophysiology. The interaction of dietary exposure with the genome is referred to as which encompasses both and It is focused on revealing the biological mechanisms that entail both the acute and persistent genome-nutrient interactions that influence health and it may represent a promising field of study to improve both clinical and health nutrition practices. Thus, the premise of this review is to discuss the relevance of personalized nutritional advices as a novel therapeutic approach in NAFLD tailored management.
Topics: Animals; Biomarkers; Diet; Disease Susceptibility; Energy Metabolism; Genetic Predisposition to Disease; Genetic Variation; Humans; Non-alcoholic Fatty Liver Disease; Nutrigenomics; Nutritional Status; Risk Factors
PubMed: 32340286
DOI: 10.3390/ijms21082986 -
International Journal of Molecular... Jan 2021There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].
There is no single global definition of a rare disease, and for different geographical areas the definition is based on the disease occurrence in that population [...].
Topics: Biomarkers; Disease Management; Disease Susceptibility; Humans; Rare Diseases
PubMed: 33445477
DOI: 10.3390/ijms22020673 -
Journal of Clinical Immunology Aug 2019WHIM syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and... (Review)
Review
WHIM syndrome is a rare combined primary immunodeficiency disease named by acronym for the diagnostic tetrad of warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow; monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. WHIM syndrome is usually caused by autosomal dominant mutations in the G protein-coupled chemokine receptor CXCR4 that impair desensitization, resulting in enhanced and prolonged G protein- and β-arrestin-dependent responses. Accordingly, CXCR4 antagonists have shown promise as mechanism-based treatments in phase 1 clinical trials. This review is based on analysis of all 105 published cases of WHIM syndrome and covers current concepts, recent advances, unresolved enigmas and controversies, and promising future research directions.
Topics: Adaptive Immunity; Alleles; Combined Modality Therapy; Diagnosis, Differential; Disease Management; Disease Susceptibility; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunity, Innate; Mutation; Phenotype; Precision Medicine; Primary Immunodeficiency Diseases; Warts
PubMed: 31313072
DOI: 10.1007/s10875-019-00665-w