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Journal of Pediatric Hematology/oncology May 2023Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal systemic inflammation disease in children. The most common cause is Epstein-Barr virus (EBV) infection....
BACKGROUND
Hemophagocytic lymphohistiocytosis (HLH) is a potentially fatal systemic inflammation disease in children. The most common cause is Epstein-Barr virus (EBV) infection. MHC class I polypeptide-related sequence B (MICB) is a membrane protein inducibly expressed upon cellular stress, viral infection, or malignant transformation, thus marking these cells for clearance through natural killer group 2 member D-positive lymphocytes. MICB can be released into plasma through several mechanisms, reducing NK cell cytotoxicity.
METHODS
We conducted clinical research on HLH patients and cell research in vitro. In the retrospective clinical part, 112 HLH patients (including EBV-HLH group and non-EBV-HLH group), 7 infectious mononucleosis patients, and 7 chronic active EBV infection patients were treated in Beijing Children's Hospital, affiliated with Capital Medical University, from January 2014 to December 2020, were enrolled in this study. Real-time quantitative polymerase chain reaction, standard enzyme-linked immunosorbent assay methods, and lactate dehydrogenase release tests were used to examine the expression of MICB mRNA, the soluble MICB (sMICB) levels, and the activity of NK cells in those patients. In vitro research, MICB overexpression-vector virus, MICB knockdown-vector virus, and empty-vector virus were transfected into two kinds of target cells, such as K562 and MCF7. The level of sMICB and NK cell killing activity between other groups was compared. Finally, we compared NK92 cell killing activity in different concentrations of sMICB.
RESULTS
In clinical studies, compared with the non-EBV-HLH group, the EBV-HLH group had lower NK cell killing activity ( P < 0.05). The level of sMICB in the EBV-HLH group was significantly higher than in non-EBV-HLH, infectious mononucleosis, and chronic active EBV infection patients ( P <0.05). A high level of sMICB was associated with poor treatment response and poor prognosis ( P <0. 05). Cellular studies showed that an increased level of membrane MICB could positively correlate with the killing activity of NK92 cells ( P <0. 05), and a high level of sMICB (1250 to 5000pg/ml) could reduce the killing activity of NK92 cells ( P < 0.05). A high level of sMICB (2500pg/ml) could increase the release of cytokines from NK92 cells.
CONCLUSION
The expression level of sMICB in EBV-HLH patients increased, and a high level of sMICB at the initial onset indicated a poor treatment response. The killing activity of NK cells in EBV-HLH patients decreased more significantly. The high level of sMICB may inhibit the killing activity but increase the release of cytokines of NK92 cells.
Topics: Child; Humans; Clinical Relevance; Cytokines; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Infectious Mononucleosis; Lymphohistiocytosis, Hemophagocytic; Retrospective Studies
PubMed: 36898046
DOI: 10.1097/MPH.0000000000002652 -
Journal of Medical Virology May 2016In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult... (Meta-Analysis)
Meta-Analysis Review
In this meta-analysis, we evaluated the diagnostic role of Epstein-Barr virus deoxyribonucleic acid detection and quantitation in the serum of pediatric and young adult patients with infectious mononucleosis. The primary outcome of this meta-analysis was the sensitivity and specificity of Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) detection and quantitation using polymerase chain reaction (PCR). A systematic review and meta-analysis was performed by searching for articles that were published through September 24, 2014 in the following databases: Medline, Cochrane, EMBASE, and Google Scholar. The following keywords were used for the search: "Epstein-Barr virus," "infectious mononucleosis," "children/young adults/infant/pediatric," and "polymerase chain reaction or PCR." Three were included in this analysis. We found that for detection by PCR, the pooled sensitivity for detecting EBV DNA was 77% (95%CI, 66-86%) and the pooled specificity for was 98% (95%CI, 93-100%). Our findings indicate that this PCR-based assay has high specificity and good sensitivity for detecting of EBV DNA, indicating it may useful for identifying patients with infectious mononucleosis. This assay may also be helpful to identify young athletic patients or highly physically active pediatric patients who are at risk for a splenic rupture due to acute infectious mononucleosis.
Topics: Adolescent; Adult; Child; Child, Preschool; DNA, Viral; Female; Herpesvirus 4, Human; Humans; Infant; Infectious Mononucleosis; Male; Molecular Diagnostic Techniques; Real-Time Polymerase Chain Reaction; Sensitivity and Specificity; Viral Load; Young Adult
PubMed: 26455510
DOI: 10.1002/jmv.24402 -
Cancer Causes & Control : CCC May 2020We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.
PURPOSE
We explored the interaction between non-Hodgkin lymphoma (NHL), infectious mononucleosis (IM) history, and immune-related genotypes in a pooled case-control analysis.
METHODS
A total of 7,926 NHL patients and 10,018 controls from 12 case-control studies were included. Studies were conducted during various time periods between 1988 and 2008, and participants were 17-96 years of age at the time of ascertainment/recruitment. Self-reported IM history and immune response genotypes were provided by the InterLymph Data Coordinating Center at Mayo Clinic. Odds ratios (OR) were estimated using multivariate logistic regression, and interactions were estimated using the empirical Bayes method. P was used to account for multiple comparisons.
RESULTS
There was evidence of an interaction effect between IM history and two variants on T-cell lymphoma (TCL) risk: rs1143627 in interleukin-1B (IL1B) (p = 0.04, OR = 0.09, 95% confidence interval [CI] 0.01, 0.87) and rs1800797 in interleukin-6 (IL6) (p = 0.03, OR = 0.08, 95% CI 0.01, 0.80). Neither interaction effect withstood adjustment for multiple comparisons. There were no statistically significant interactions between immune response genotypes and IM on other NHL subtypes.
CONCLUSIONS
Genetic risk variants in IL1B and IL6 may affect the association between IM and TCL, possibly by influencing T-cell activation, growth, and differentiation in the presence of IM, thereby decreasing risk of immune cell proliferation.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bayes Theorem; Case-Control Studies; Female; Genotype; Humans; Infectious Mononucleosis; Lymphoma, Non-Hodgkin; Male; Middle Aged; Risk Factors; Self Report; Young Adult
PubMed: 32124188
DOI: 10.1007/s10552-020-01266-4 -
Multiple Sclerosis (Houndmills,... Apr 2020Multiple sclerosis (MS) is a chronic demyelinating disease that is associated with permanent disability and low quality of life. Development of MS is attributed to a... (Review)
Review
Multiple sclerosis (MS) is a chronic demyelinating disease that is associated with permanent disability and low quality of life. Development of MS is attributed to a combination of genetic and environmental factors. Genome-wide association studies revealed more than 200 variants that are associated with risk of MS. An umbrella review showed that smoking, history of infectious mononucleosis, and anti-Epstein-Barr virus nuclear antigen (anti-EBNA) immunoglobulin G (IgG) seropositivity are credible risk factors of MS. In the present narrative review, we updated our published umbrella review, showing that body mass index in childhood and adolescence and anti-viral capsid antigen (anti-VCA) IgG seropositivity are additional credible risk factors of MS. In addition, we discuss the findings from Mendelian randomization studies, which present evidence for a potential causal role of serum vitamin D and adulthood body mass index on risk of MS. Finally, we discuss the potential limitations of meta-analyses, umbrella reviews, and Mendelian randomization studies in the search for risk factors of MS.
Topics: Adolescent; Adult; Antigens, Viral; Body Mass Index; Child; Humans; Infectious Mononucleosis; Mendelian Randomization Analysis; Meta-Analysis as Topic; Multiple Sclerosis; Smoking
PubMed: 32249718
DOI: 10.1177/1352458519872664 -
PeerJ 2023Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the...
Infectious mononucleosis in children and differences in biomarker levels and other features between disease caused by Epstein-Barr virus and other pathogens: a single-center retrospective study in China.
BACKGROUND
Infectious mononucleosis (IM) is a common viral infection that typically presents with fever, pharyngitis and cervical lymphadenopathy. Our aim was to identify the different pathogens causing IM in children admitted to our hospital and to analyze the differences in features of infection with different organisms.
METHODS
We retrospectively analyzed the data of children aged 0-17 years admitted to Wuhan Children's Hospital during 2013-2022 with IM. We compared symptoms, physical findings, blood counts, and serum biomarkers between patients with IM due to Epstein-Barr virus (EBV) and IM due to other pathogens.
RESULTS
Among 1480 enrolled children, 1253 (84.66%) had EBV infection, 806 (54.46%) had infection, 796 (53.78%) had cytomegalovirus infection, 159 (10.74%) had parvovirus infection, 38 (2.57%) had influenza virus infection, and 25 (1.69%) had adenovirus infection. Receiver operating characteristic curves were used to determine the area under the curve for alanine transaminase (ALT), aspartate transaminase (AST), Alkaline phosphatase (ALP), total bilirubin (TBil), indirect bilirubin (IBil) levels to assess liver damage, and for creatine kinase (CK), CK-MB, and lactate dehydrogenase (LDH) levels to assess myocardial damage. The optimal cutoff values of these biomarkers were then determined. In multivariate analysis, elevated ALT, AST, ALP, TBil, and IBil were independently associated with liver damage, and age <3 years, CK, CK-MB, and LDH with myocardial damage.
CONCLUSION
Evaluation of biomarkers and pathogen detection may help physicians to take preventive actions to avoid serious complications in children with infectious mononucleosis.
Topics: Humans; Child; Infectious Mononucleosis; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Retrospective Studies; Biomarkers
PubMed: 37041976
DOI: 10.7717/peerj.15071 -
BMC Infectious Diseases Feb 2022Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed...
BACKGROUND
Infectious mononucleosis, a common disease in children and young adults, is often accompanied by elevated transaminase levels and rarely, liver failure. This study aimed to determine whether adenosine deaminase is a marker of severity in children with infectious mononucleosis, especially those with elevated alanine transaminase levels.
METHODS
This case-control study was conducted at the Children's Hospital of Soochow University. A total of 104 children with infectious mononucleosis and 50 controls with other acute infections and fever, tonsillitis, or lymphadenitis, were enrolled in the study. Among the 104 children with infectious mononucleosis, 54 had normal alanine transaminase levels and 50 had elevated alanine transaminase levels. The children's clinical and laboratory data were analyzed to assess the diagnostic value of adenosine deaminase in the three groups.
RESULTS
The adenosine deaminase level in the infectious mononucleosis group was significantly higher than that in the control group (P < 0.001). The adenosine deaminase levels were highly correlated with lymphocyte count, CD3CD8 T cells (%), CD4/CD8 ratio, and CD3CD19 (%) (r > 0.7, P < 0.01). The sensitivity and specificity of adenosine deaminase in predicting children with infectious mononucleosis were 97.1% and 94.0%, respectively. Furthermore, multivariate regression analysis revealed that adenosine deaminase level was a risk factor for elevated alanine transaminase in children with infectious mononucleosis.
CONCLUSIONS
Adenosine deaminase may be a marker of the severity of infectious mononucleosis in children, and a predictor of elevated alanine transaminase in children with infectious mononucleosis.
Topics: Adenosine Deaminase; CD8-Positive T-Lymphocytes; Case-Control Studies; Herpesvirus 4, Human; Humans; Infectious Mononucleosis
PubMed: 35189820
DOI: 10.1186/s12879-022-07150-7 -
Gastroenterologia Y Hepatologia Feb 2022
Topics: Adult; Amoxicillin; Anti-Bacterial Agents; Drug Eruptions; Hepatomegaly; Herpesvirus 4, Human; Humans; Infectious Mononucleosis; Male; Splenomegaly; Symptom Assessment
PubMed: 33183890
DOI: 10.1016/j.gastrohep.2020.08.013 -
BMJ Case Reports Nov 2022
Topics: Humans; Infectious Mononucleosis
PubMed: 36384885
DOI: 10.1136/bcr-2022-252839 -
Minerva Pediatrica Oct 2018Infectious mononucleosis (IM) is a common disease of adolescents and young adults, characterized by a specific triad of symptoms represented by fever, sore throat and... (Comparative Study)
Comparative Study
BACKGROUND
Infectious mononucleosis (IM) is a common disease of adolescents and young adults, characterized by a specific triad of symptoms represented by fever, sore throat and lymphadenopathy. IM may also affect older adults, with different, more intense signs and symptoms such as fatigue, general malaise, and diffuse body pain. The aim of this four-week-registry study was to evaluate the effects of Robuvit® supplementation on the main consequences of mononucleosis, particularly fatigue, in otherwise healthy adults.
METHODS
All patients enrolled in this registry study experienced an episode of IM characterized by fatigue, a general feeling of unwellness, diffuse body and muscular pain, leukocytosis, and high levels of oxidative stress, at least 2 to 4 weeks prior to inclusion. Fever had already resolved at inclusion. All included patients were positively tested for the Epstein-Barr virus (EBV). Subjects were divided in two groups: those receiving the standard management (SM, N.=26; vitamin B, C, and D, balanced healthy diet, regular sleeping schedule, physical activity, 2 mg copper), and those treated with SM plus Robuvit® (N.=24) supplementation (300 mg/day).
RESULTS
Supplementation with Robuvit® was safe, overall tolerability was good, and no side effects were reported. All patients completed the four-week treatment. After 4 weeks of treatment, a significant reduction in the rate of symptoms was evident in the Robuvit® group compared to the control group (P<0.05).
CONCLUSIONS
Supplementation with Robuvit® is safe, well tolerated, and effective in controlling oxidative stress levels and improving fatigue and other symptoms related to IM episodes during the convalescence period.
Topics: Adult; Dietary Supplements; Fatigue; Female; Humans; Hydrolyzable Tannins; Infectious Mononucleosis; Male; Oxidative Stress; Plant Extracts; Registries; Treatment Outcome
PubMed: 30302988
DOI: 10.23736/S0026-4946.18.05213-1 -
The American Journal of the Medical... Mar 2023Liver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients...
BACKGROUND
Liver involvement during infectious mononucleosis is common, but jaundice is considered rare. This study aimed to investigate serum bilirubin concentrations in patients with infectious mononucleosis and immune abnormalities associated with jaundice.
METHODS
We report on an adult patient with monoclonal B lymphocytosis and IgM-lambda gammopathy who developed a severe icteric hepatitis during infectious mononucleosis. We then reviewed the clinical records of 389 patients admitted to the hospital with infectious mononucleosis between 1995 and 2018 (51.7% male patients; median age, 19 years; range, 15-87 years) with focus on liver abnormalities and associated factors.
RESULTS
Fifty-nine patients (15.1%) had serum bilirubin concentrations between 1.5 and 3 mg/dL, and 47 patients (12.0%) had serum bilirubin >3 mg/dL. Patients with increased bilirubin concentrations had a distinct clinical presentation, with more frequent abdominal pain, nausea and vomiting, and less frequent sore throat than patients with normal bilirubin. Age and sex were not significantly different for the patients with increased and normal serum bilirubin concentrations. The patients with increased serum bilirubin concentrations showed higher levels of immune activation markers than the patients with normal bilirubin, including blood lymphocyte counts, serum IgM, and β-microglobulin concentrations. Heterophile antibody-positive patients (88.6%) showed similar bilirubin concentrations but higher aspartate aminotransferase and alkaline phosphatase levels than their heterophile-negative counterparts. Serum bilirubin elevations normalized quickly during follow-up.
CONCLUSIONS
Transient hyperbilirubinemia is common during severe (in-hospital) infectious mononucleosis in adult patients. Patients with hyperbilirubinemia have less frequent pharyngitis symptoms and more frequent abdominal symptoms. Hyperbilirubinemia during infectious mononucleosis is associated with immune activation markers.
Topics: Adult; Humans; Male; Young Adult; Female; Infectious Mononucleosis; Herpesvirus 4, Human; Epstein-Barr Virus Infections; Jaundice; Hyperbilirubinemia; Bilirubin; Immunoglobulin M
PubMed: 36526005
DOI: 10.1016/j.amjms.2022.12.004