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Journal of Thrombosis and Haemostasis :... Apr 2018
Topics: Confounding Factors, Epidemiologic; Disease Susceptibility; Humans; Predictive Value of Tests; Risk Assessment; Risk Factors; Terminology as Topic
PubMed: 29607605
DOI: 10.1111/jth.13990 -
Immunology Feb 2022Cryptococcus neoformans is an opportunistic fungal pathogen that can cause lethal cryptococcal meningitis in immunocompromised individuals such as those with HIV/AIDS.... (Review)
Review
Cryptococcus neoformans is an opportunistic fungal pathogen that can cause lethal cryptococcal meningitis in immunocompromised individuals such as those with HIV/AIDS. In addition, cryptococcal infections occasionally arise in immunocompetent individuals or those with previously undiagnosed immunodeficiencies. The course of cryptococcosis is highly variable in both patient groups, and there is rapidly growing evidence that genetic polymorphisms may have a significant impact on the trajectory of disease. Here, we review what is currently known about the nature of these polymorphisms and their impact on host response to C. neoformans infection. Thus far, polymorphisms in Fc gamma receptors, mannose-binding lectin, Dectin-2, Toll-like receptors and macrophage colony-stimulating factor have been associated with susceptibility to cryptococcal disease. Notably, however, in some cases the impact of these polymorphisms depends on the genetic background of the population; for example, the FCGR3A 158 F/V polymorphism was associated with an increased risk of cryptococcal disease in both HIV-positive and HIV-negative white populations, but not in Han Chinese patients. In most cases, the precise mechanism by which the identified polymorphisms influence disease progression remains unclear, although impaired fungal recognition and phagocytosis by innate immune cells appears to play a major role. Finally, we highlight outstanding questions in the field and emphasize the need for future research to include more diverse populations in their genetic association studies.
Topics: Adaptive Immunity; Animals; Biomarkers; Cryptococcosis; Cryptococcus neoformans; Disease Susceptibility; Gene Expression Regulation; Genetic Predisposition to Disease; Genetic Variation; Host-Pathogen Interactions; Humans; Immunity, Innate; Immunocompromised Host; Immunogenetic Phenomena; Polymorphism, Genetic; Signal Transduction
PubMed: 34716931
DOI: 10.1111/imm.13425 -
Seminars in Immunopathology Jul 2015Type I interferons (IFNs) play a central role in the immune defense against viral infections. Type I IFN signaling is activated by pattern recognition receptors upon... (Review)
Review
Type I interferons (IFNs) play a central role in the immune defense against viral infections. Type I IFN signaling is activated by pattern recognition receptors upon sensing of viral nucleic acids and induces antiviral programs through modulation of innate and adaptive immune responses. Type I interferonopathies comprise a heterogenous group of genetically determined diseases that are characterized by inappropriate activation of type I IFN. While their phenotypic spectrum is broad, ranging from severe neurological impairment to mild cutaneous disease, systemic autoinflammation, and autoimmunity are commonly shared signs of type I interferonopathies. Although the mechanisms underlying various disease phenotypes associated with inappropriate type I IFN activation have yet to be fully elucidated, our current understanding of the molecular pathogenesis of type I interferonopathies has provided a set of candidate molecules that can be interrogated in search of targeted therapies.
Topics: Animals; Autoimmune Diseases; Disease Susceptibility; Hereditary Autoinflammatory Diseases; Host-Pathogen Interactions; Humans; Inflammation; Interferon Type I; Receptors, Immunologic; Signal Transduction
PubMed: 25998914
DOI: 10.1007/s00281-015-0500-x -
BioMed Research International 2018Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a... (Review)
Review
Nuclear casein kinase and cyclin-dependent kinase substrate 1 (NUCKS1) is a 27 kD chromosomal, highly conserved, and vertebrate-specific protein. NUCKS1 gene encodes a nuclear protein and the conserved regions of NUCKS1 contain several consensus phosphorylation sites for casein kinase II (CK2) and cyclin-dependent kinases (Cdk) and a basic DNA-binding domain. NUCKS1 is similar to the high mobility group (HMG) family which dominates chromatin remodeling and regulates gene transcription. Meanwhile, NUCKS1 is a RAD51 associated protein 1 (RAD51AP1) paralog that is significant for homologous recombination (HR) and genome stability and also a transcriptional regulator of the insulin signaling components. NUCKS1 plays an important role in DNA damage response and metabolism, participates in inflammatory immune response, and correlates with microRNA. Although there is still not enough functional information on NUCKS1, evidences suggest that NUCKS1 can be used as the biomarker of several cancers. This review summarizes the latest research on NUCKS1 about its susceptibility in diseases, expression levels, and regulatory mechanisms as well as the possible functions in reference to diseases.
Topics: Biomarkers; DNA Damage; Disease; Disease Susceptibility; Gene Expression Regulation; Genetic Predisposition to Disease; Humans; Nuclear Proteins
PubMed: 29619377
DOI: 10.1155/2018/7969068 -
Critical Care (London, England) Sep 2019Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility... (Review)
Review
Most people exposed to a new flu virus do not notice any symptoms. A small minority develops critical illness. Some of this extremely broad variation in susceptibility is explained by the size of the initial inoculum or the influenza exposure history of the individual; some is explained by generic host factors, such as frailty, that decrease resilience following any systemic insult. Some demographic factors (pregnancy, obesity, and advanced age) appear to confer a more specific susceptibility to severe illness following infection with influenza viruses. As with other infectious diseases, a substantial component of susceptibility is determined by host genetics. Several genetic susceptibility variants have now been reported with varying levels of evidence. Susceptible hosts may have impaired intracellular controls of viral replication (e.g. IFITM3, TMPRS22 variants), defective interferon responses (e.g. GLDC, IRF7/9 variants), or defects in cell-mediated immunity with increased baseline levels of systemic inflammation (obesity, pregnancy, advanced age). These mechanisms may explain the prolonged viral replication reported in critically ill patients with influenza: patients with life-threatening disease are, by definition, abnormal hosts. Understanding these molecular mechanisms of susceptibility may in the future enable the design of host-directed therapies to promote resilience.
Topics: Adult; Age Factors; Disease Susceptibility; Female; GATA2 Transcription Factor; Humans; Influenza A virus; Influenza, Human; Interferon Regulatory Factor-7; Interferon-Stimulated Gene Factor 3, gamma Subunit; Obesity; Pregnancy; Pregnancy Complications, Infectious
PubMed: 31488196
DOI: 10.1186/s13054-019-2566-7 -
Multiple Sclerosis (Houndmills,... Apr 2020Sex differences in the incidence or severity of disease characterize many autoimmune and neurodegenerative diseases. Multiple sclerosis is a complex disease with both... (Review)
Review
Sex differences in the incidence or severity of disease characterize many autoimmune and neurodegenerative diseases. Multiple sclerosis is a complex disease with both autoimmune and neurodegenerative aspects and is characterized by sex differences in susceptibility and progression. Research in the study sex differences is a way to capitalize on a known clinical observation, mechanistically disentangle it at the laboratory bench, then translate basic research findings back to the clinic as a novel treatment trial tailored to optimally benefit each sex. This "Bedside to Bench to Bedside" approach based on sex differences in MS will be reviewed here, first for disease susceptibility then for disability progression.
Topics: Disease Progression; Disease Susceptibility; Female; Humans; Male; Multiple Sclerosis; Sex Characteristics
PubMed: 31965884
DOI: 10.1177/1352458519892491 -
Internal and Emergency Medicine Mar 2020Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number...
Defective spleen function increases susceptibility to bacterial infections which can be prevented by vaccine prophylaxis. Splenic hypofunction can be found in a number of autoimmune disorders; however, no data are available regarding autoimmune atrophic gastritis (AAG), autoimmune enteropathy (AIE) and autoimmune liver disease (AILD). Peripheral blood samples from patients with AAG (n = 40), AIE (n = 3) and AILD (n = 40) were collected. Patients affected by autoimmune disorders already known to be associated with splenic hypofunction, i.e. coeliac disease (CD) and ulcerative colitis (UC), were included as disease controls, while splenectomised patients and healthy subjects were evaluated as positive and negative controls, respectively. Counting of erythrocytes with membrane abnormalities, i.e. pitted red cells, was used as an indicator of spleen function (normal upper limit 4%). Defective splenic function was observed in 22 of the 40 patients with AAG (55.0%), in two of the three patients with AIE (66.6%) and in 35 of the 40 patients with AILD (87.5%). As expected, in untreated CD, refractory CD and UC there was a high prevalence of hyposplenism (43.7%, 88.2% and 54.4%, respectively). Due to the high prevalence of splenic hypofunction, patients with AAG, AILD and AIE should undergo pitted red cell evaluation and, if hyposplenic, they should be candidate to vaccine prophylaxis against encapsulated bacteria.
Topics: Adult; Aged; Aged, 80 and over; Autoimmune Diseases; Disease Susceptibility; Female; Gastrointestinal Diseases; Humans; Italy; London; Male; Middle Aged; Prospective Studies; Spleen; Splenic Diseases; Statistics, Nonparametric
PubMed: 31214883
DOI: 10.1007/s11739-019-02129-w -
Psychiatry Research Aug 2019In recent years schizophrenia has been assumed to be largely a genetic disease with heritability estimates, derived primarily from family and twin studies, of 80%-85%.... (Review)
Review
In recent years schizophrenia has been assumed to be largely a genetic disease with heritability estimates, derived primarily from family and twin studies, of 80%-85%. However, the results of genetic research on schizophrenia have not yielded results consistent with that estimate of heritability. In particular, extensive genetic studies have not led to new methods for diagnosis and treatment. An examination of the twin studies on which heritability is based shows why such studies exaggerate the genetic component of schizophrenia. In addition, the effects of infectious agents such as Toxoplasma gondii and the composition of the microbiome can produce a clinical picture that would also appear to be largely genetic due to familial aggregation and a role for a partial genetic contribution to the immune system. It is concluded that the genetic component of schizophrenia may have been overestimated and an increased focus on gene-environmental interactions is likely to accelerate research progress on this disease.
Topics: Disease Susceptibility; Gene-Environment Interaction; Humans; Schizophrenia; Twin Studies as Topic
PubMed: 31200193
DOI: 10.1016/j.psychres.2019.06.006 -
The American Journal of Psychiatry Jan 2020A large body of evidence has demonstrated that exposure to childhood maltreatment at any stage of development can have long-lasting consequences. It is associated with a... (Review)
Review
A large body of evidence has demonstrated that exposure to childhood maltreatment at any stage of development can have long-lasting consequences. It is associated with a marked increase in risk for psychiatric and medical disorders. This review summarizes the literature investigating the effects of childhood maltreatment on disease vulnerability for mood disorders, specifically summarizing cross-sectional and more recent longitudinal studies demonstrating that childhood maltreatment is more prevalent and is associated with increased risk for first mood episode, episode recurrence, greater comorbidities, and increased risk for suicidal ideation and attempts in individuals with mood disorders. It summarizes the persistent alterations associated with childhood maltreatment, including alterations in the hypothalamic-pituitary-adrenal axis and inflammatory cytokines, which may contribute to disease vulnerability and a more pernicious disease course. The authors discuss several candidate genes and environmental factors (for example, substance use) that may alter disease vulnerability and illness course and neurobiological associations that may mediate these relationships following childhood maltreatment. Studies provide insight into modifiable mechanisms and provide direction to improve both treatment and prevention strategies.
Topics: Child; Child Abuse; Comorbidity; Disease Susceptibility; Humans; Mood Disorders; Risk Factors
PubMed: 31537091
DOI: 10.1176/appi.ajp.2019.19010020 -
Current Topics in Developmental Biology 2016It is thought that most structural birth defects are caused by a complex combination of genetic and environmental factors that interact to interfere with morphogenetic... (Review)
Review
It is thought that most structural birth defects are caused by a complex combination of genetic and environmental factors that interact to interfere with morphogenetic processes. It is important not only to identify individual genetic and environmental risk factors for particular defects but also to identify which environmental factors interact specifically with which genetic variants that predispose to the same defect. Genomic and epidemiological studies are critical to this end. Development and analysis of model systems will also be essential for this goal, as well as for understanding the mechanisms that underlie specific gene-environment interactions.
Topics: Congenital Abnormalities; Disease Susceptibility; Gene-Environment Interaction; Genetic Variation; Humans; Risk Factors
PubMed: 26970642
DOI: 10.1016/bs.ctdb.2015.12.010