The asymmetrical distribution of the cellular organelles inside the cell is maintained by a group of cell polarity proteins. The maintenance of polarity is one of the vital host defense mechanisms against pathogens, and the loss of it contributes to infection facilitation and cancer progression. Studies have suggested that infection of viruses and bacteria alters cell polarity. Helicobacter pylori and Epstein-Barr virus are group I carcinogens involved in the progression of multiple clinical conditions besides gastric cancer (GC) and Burkitt's lymphoma, respectively. Moreover, the coinfection of both these pathogens contributes to a highly aggressive form of GC. H. pylori and EBV target the host cell polarity complexes for their pathogenesis. H. pylori-associated proteins like CagA, VacA OipA, and urease were shown to imbalance the cellular homeostasis by altering the cell polarity. Similarly, EBV-associated genes LMP1, LMP2A, LMP2B, EBNA3C, and EBNA1 also contribute to altered cell asymmetry. This review summarized all the possible mechanisms involved in cell polarity deformation in H. pylori and EBV-infected epithelial cells. We have also discussed deregulated molecular pathways like NF-κB, TGF-β/SMAD, and β-catenin in H. pylori, EBV, and their coinfection that further modulate PAR, SCRIB, or CRB polarity complexes in epithelial cells.
- MeSH
- Helicobacter pylori * genetika MeSH
- infekce virem Epsteina-Barrové * mikrobiologie patologie MeSH
- infekce vyvolané Helicobacter pylori * mikrobiologie MeSH
- koinfekce * mikrobiologie MeSH
- lidé MeSH
- nádory žaludku * genetika mikrobiologie patologie MeSH
- polarita buněk MeSH
- virové proteiny MeSH
- virus Epsteinův-Barrové genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Deficience kyselé lipázy (LAL-D) je geneticky podmíněné progresivní onemocnění s významnou morbiditou a mortalitou u dětí i dospělých. Hlavními klinickými příznaky jsou kombinace jaterní dysfunkce a dyslipidemie v důsledku střádání esterů cholesterolu a triacylglycerolů v celém organismu, převážně v játrech, slezině, gastrointestinálním traktu a ve stěnách cév. LAL-D má dostupnou přesnou diagnostiku biochemickým průkazem aktivity kyselé lyzozomální lipázy (LAL) a v posledních letech je dobře řešitelná kauzálně podáním rekombinantní enzymové substituční terapie.
Lysosomal acid lipase deficiency (LAL-D) is a genetically determined progressive disease with significant morbidity and mortality in children and adults. The main clinical features include a combination of hepatic dysfunction and dyslipidemia as a consequence of cholesterol ester and triglyceride accumulation throughout the body, predominantly in the liver, spleen, gastrointestinal tract and vessel walls. It has an accurate diagnosis available by biochemical demonstration of acid lysosomal lipase (LAL) activity and in recent years has been well addressed by causal therapy based on recombinant enzyme replacement therapy.
- MeSH
- dyslipidemie enzymologie etiologie metabolismus MeSH
- kazuistiky jako téma MeSH
- lidé MeSH
- lipasa analýza metabolismus nedostatek MeSH
- nemoc ze střádání esterů cholesterolu * diagnóza enzymologie farmakoterapie MeSH
- nemoci jater diagnóza enzymologie etiologie klasifikace MeSH
- předškolní dítě MeSH
- virus Epsteinův-Barrové patogenita MeSH
- Wolmanova nemoc * diagnóza enzymologie farmakoterapie MeSH
- ztučnělá játra diagnóza enzymologie etiologie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- Publikační typ
- přehledy MeSH
After a decade of human urinary microbiota research, little is known about the composition of the urinary virome and its association with health and disease. This study aimed to investigate the presence of 10 common DNA viruses in human urine and their putative association with bladder cancer (BC). Catheterized urine samples were collected from patients undergoing endoscopic urological procedures under anesthesia. After DNA extraction from the samples, viral DNA sequences were detected using real-time PCR. Viruria rates were compared between BC patients and controls. A total of 106 patients (89 males and 17 females) were included in the study. Fifty-seven (53.8%) were BC patients and 49 (46.2%) had upper urinary tract stones or bladder outlet obstruction. The viruses detected in the urine were human cytomegalovirus (2.0%), Epstein-Barr virus (6.0%), human herpesvirus-6 (12.5%), human papillomavirus (15.2%), BK polyomavirus (15.5%), torque teno virus (44.2%), and JC polyomavirus (47.6%), while no adenoviruses, herpes simplex virus 1 and 2, or parvoviruses were found. There were statistically significant differences in HPV viruria rates between cancer patients and controls (24.5% vs. 4.3%, p=0.032 after adjustment for age and gender). Viruria rates increased from benign to non-muscle-invasive and muscle-invasive tumors. Patients with a history of BC have higher HPV viruria rates than controls. Whether this relationship is a causal one remains to be established by further research.
The development of a second malignancy after the diagnosis of childhood acute lymphoblastic leukemia (ALL) is a rare event. Certain second malignancies have been linked with specific elements of leukemia therapy, yet the etiology of most second neoplasms remains obscure and their optimal management strategies are unclear. This is a first comprehensive report of non-Hodgkin lymphomas (NHLs) following pediatric ALL therapy, excluding stem-cell transplantation. We analyzed data of patients who developed NHL following ALL diagnosis and were enrolled in 12 collaborative pediatric ALL trials between 1980-2018. Eighty-five patients developed NHL, with mature B-cell lymphoproliferations as the dominant subtype (56 of 85 cases). Forty-six of these 56 cases (82%) occurred during or within 6 months of maintenance therapy. The majority exhibited histopathological characteristics associated with immunodeficiency (65%), predominantly evidence of Epstein-Barr virus-driven lymphoproliferation. We investigated 66 cases of post-ALL immunodeficiency-associated lymphoid neoplasms, 52 from our study and 14 additional cases from a literature search. With a median follow-up of 4.9 years, the 5-year overall survival for the 66 patients with immunodeficiency-associated lymphoid neoplasms was 67.4% (95% confidence interval [CI], 56-81). Five-year cumulative risks of lymphoid neoplasm- and leukemia-related mortality were 20% (95% CI, 10.2-30) and 12.4% (95% CI, 2.7-22), respectively. Concurrent hemophagocytic lymphohistiocytosis was associated with increased mortality (hazard ratio, 7.32; 95% CI, 1.62-32.98; P = .01). A large proportion of post-ALL lymphoid neoplasms are associated with an immunodeficient state, likely precipitated by ALL maintenance therapy. Awareness of this underrecognized entity and pertinent diagnostic tests are crucial for early diagnosis and optimal therapy.
- MeSH
- akutní lymfatická leukemie * terapie komplikace MeSH
- dítě MeSH
- infekce virem Epsteina-Barrové * komplikace diagnóza MeSH
- lidé MeSH
- lymfom * komplikace MeSH
- nehodgkinský lymfom * patologie MeSH
- sekundární malignity * MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
IgA nephropathy (IgAN) is an autoimmune disease in which poorly galactosylated IgA1 is the antigen recognized by naturally occurring anti-glycan antibodies, leading to formation of nephritogenic circulating immune complexes. Incidence of IgAN displays geographical and racial disparity: common in Europe, North America, Australia, and east Asia, uncommon in African Americans, many Asian and South American countries, Australian Aborigines, and rare in central Africa. In analyses of sera and cells from White IgAN patients, healthy controls, and African Americans, IgAN patients exhibited substantial enrichment for IgA-expressing B cells infected with Epstein-Barr virus (EBV), leading to enhanced production of poorly galactosylated IgA1. Disparities in incidence of IgAN may reflect a previously disregarded difference in the maturation of the IgA system as related to the timing of EBV infection. Compared with populations with higher incidences of IgAN, African Americans, African Blacks, and Australian Aborigines are more frequently infected with EBV during the first 1-2 years of life at the time of naturally occurring IgA deficiency when IgA cells are less numerous than in late childhood or adolescence. Therefore, in very young children EBV enters "non-IgA" cells. Ensuing immune responses prevent infection of IgA B cells during later exposure to EBV at older ages. Our data implicate EBV-infected cells as the source of poorly galactosylated IgA1 in circulating immune complexes and glomerular deposits in patients with IgAN. Thus, temporal differences in EBV primo-infection as related to naturally delayed maturation of the IgA system may contribute to geographic and racial variations in incidence of IgAN.
- MeSH
- černoši MeSH
- dítě MeSH
- IgA nefropatie * epidemiologie etnologie MeSH
- imunoglobulin A MeSH
- imunokomplex MeSH
- infekce virem Epsteina-Barrové * epidemiologie etnologie MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Austrálie MeSH
Rheumatoid arthritis (RA) is one of the world's most prevalent inflammatory autoimmune diseases, affecting between 0.4 and 1.3% of the population. The susceptibility to RA appears to be influenced by a complex interaction between a favorable genetic background and the existence of a specific immune reaction against a wide range of environmental variables. Among the known environmental variables, infections are believed to have a significant role in promoting the formation of autoimmune disorders, which are frequently caused by specific microorganisms. Infections have been linked to RA in recent medical studies. In this study, we selected the most prevalent infections associated with RA from the literature and described the data confirming their pathogenic role in RA. Our investigation included Mycobacterium, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Proteus mirabilis, Epstein-Barr virus, parvovirus, and Prevotella copri.
- MeSH
- infekce virem Epsteina-Barrové * komplikace MeSH
- lidé MeSH
- revmatoidní artritida * komplikace genetika MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
PURPOSE: Heterozygous mutations in CTLA4 lead to an inborn error of immunity characterized by immune dysregulation and immunodeficiency, known as CTLA-4 insufficiency. Cohort studies on CTLA4 mutation carriers showed a reduced penetrance (around 70%) and variable disease expressivity, suggesting the presence of modifying factors. It is well studied that infections can trigger autoimmunity in humans, especially in combination with a genetic predisposition. METHODS: To investigate whether specific infections or the presence of specific persisting pathogens are associated with disease onset or severity in CTLA-4 insufficiency, we have examined the humoral immune response in 13 CTLA4 mutation carriers, seven without clinical manifestation and six with autoimmune manifestations, but without immunoglobulin replacement therapy against cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1/2 (HSV 1/2), parvovirus B19 and Toxoplasma gondii. Additionally, we have measured FcγRIII/CD16A activation by EBV-specific IgG antibodies to examine the functional capabilities of immunoglobulins produced by CTLA4 mutation carriers. RESULTS: The seroprevalence between affected and unaffected CTLA4 mutation carriers did not differ significantly for the examined pathogens. Additionally, we show here that CTLA4 mutation carriers produce EBV-specific IgG, which are unimpaired in activating FcγRIII/CD16A. CONCLUSIONS: Our results show that the investigated pathogens are very unlikely to trigger the disease onset in CTLA-4-insufficient individuals, and their prevalence is not correlated with disease severity or expressivity.
- MeSH
- antigen CTLA-4 genetika MeSH
- imunoglobulin G MeSH
- infekce virem Epsteina-Barrové * komplikace epidemiologie MeSH
- lidé MeSH
- protilátky virové MeSH
- séroepidemiologické studie MeSH
- virus Epsteinův-Barrové * fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Protein aggregates and abnormal proteins are toxic and associated with neurodegenerative diseases. There are several mechanisms to help cells get rid of aggregates but little is known on how cells prevent aggregate-prone proteins from being synthesised. The EBNA1 of the Epstein-Barr virus (EBV) evades the immune system by suppressing its own mRNA translation initiation in order to minimize the production of antigenic peptides for the major histocompatibility (MHC) class I pathway. Here we show that the emerging peptide of the disordered glycine-alanine repeat (GAr) within EBNA1 dislodges the nascent polypeptide-associated complex (NAC) from the ribosome. This results in the recruitment of nucleolin to the GAr-encoding mRNA and suppression of mRNA translation initiation in cis. Suppressing NAC alpha (NACA) expression prevents nucleolin from binding to the GAr mRNA and overcomes GAr-mediated translation inhibition. Taken together, these observations suggest that EBNA1 exploits a nascent protein quality control pathway to regulate its own rate of synthesis that is based on sensing the nascent GAr peptide by NAC followed by the recruitment of nucleolin to the GAr-encoding RNA sequence.
- MeSH
- alanin MeSH
- fosfoproteiny MeSH
- glycin MeSH
- infekce virem Epsteina-Barrové * MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- peptidy genetika MeSH
- proteinové agregáty MeSH
- proteiny vázající RNA metabolismus MeSH
- virus Epsteinův-Barrové - jaderné antigeny metabolismus MeSH
- virus Epsteinův-Barrové * genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- cvičení * imunologie škodlivé účinky MeSH
- dospělí MeSH
- dysbióza MeSH
- imunoterapie * MeSH
- lidé MeSH
- mladiství MeSH
- nemoci dýchací soustavy etiologie imunologie MeSH
- nemoci střev terapie MeSH
- nesnášenlivost laktózy MeSH
- počet lymfocytů MeSH
- sérologické testy MeSH
- sportovci MeSH
- virové nemoci * imunologie terapie MeSH
- virus Epsteinův-Barrové účinky léků MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
PURPOSE OF REVIEW: To discuss recent changes in the multiple sclerosis (MS) treatment algorithm and to present therapies currently in MS clinical trials. RECENT FINDINGS: High efficacy disease modifying therapies are optimally beneficial when used in the early, inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of MS. Multiple therapies targeting remyelination failed to provide conclusive evidence of broad therapeutic benefit; however, more targeted approaches offer hope that myelin repair might be achieved resulting in specific clinical improvements. Strategies targeting chronic Epstein-Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions. SUMMARY: A striking number of diverse treatments under investigation bodes well for development of better and more effective therapies in MS.
- MeSH
- algoritmy MeSH
- infekce virem Epsteina-Barrové * MeSH
- lidé MeSH
- remyelinizace * MeSH
- roztroušená skleróza * farmakoterapie MeSH
- virus Epsteinův-Barrové MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
