scholarly journals The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer

Cells ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 1498
Author(s):  
Irene Gullo ◽  
Catarina Costa ◽  
Susana L. Silva ◽  
Cristina Ferreira ◽  
Adriana Motta ◽  
...  

Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.

2021 ◽  
Vol 14 (10) ◽  
Author(s):  
Mahin Ahangar Oskouee ◽  
Jamal Sarvari ◽  
Afagh Moattari ◽  
Ahmad Habibi ◽  
Amir Taher Eftehkar Sadat

Background: Given the fact that viral infections play an important role, either directly or indirectly, in around 20 percent of human cancers, this study aimed at investigating the potential association of Epstein–Barr virus (EBV) and cytomegalovirus (CMV) infections in esophageal cancer that is the sixth most common cause of cancer-related deaths. Methods: In this case-control study, a total of 200 paraffin-embedded biopsies of cancerous and benign esophageal tissues were gathered from the biopsy bank of Imam Reza Hospital, Tabriz, Iran in 2017. All samples were first deparaffinized, and then subjected to commercial DNA extraction. The quality of extracted DNA was evaluated by amplification of the beta globulin gene. Identification of EBV and CMV DNA was performed using primers designed for the EBER region of EBV and the immediate early (IE) region of the CMV genome, respectively. Results: The mean age of the subjects in the test and control groups was 52.2 (17.1) and 59.9 (18.9), respectively. The distribution of gender (male/female) in patient and control groups was 54/46 and 53/47, respectively. Our results showed that the frequency of EBV (P < 0.001) and CMV (P < 0.001) in cancerous samples was statistically higher than control group. Moreover, in the cancerous group the rate of EBV was significantly higher in the esophageal adenocarcinomas (EAC) sample (12 out of 70) than esophageal squamous cell carcinomas (ESCC) (0 out of 30) (P = 0.016) but, in the ESCC group, 17 out of 30 subjects were positive for CMV which was significantly higher in comparison with EAC patients (1 out of 70) (P < 0.001). Conclusions: Findings indicated that EBV and CMV might be contributed to the pathogenesis of EAC and ESCC types of esophageal carcinoma, respectively, although further studies are warranted.


Author(s):  
Ronan J. Kelly

PD-L1 upregulation occurs in approximately 40% of gastroesophageal cancers. However, unlike other solid tumors, there is minimal PD-L1 expressed on the cancer cells; rather, expression occurs predominantly on infiltrating myeloid cells. Preliminary clinical data involving single-agent PD-1/PD-L1 inhibitors in metastatic gastroesophageal cancer have reported response rates of 22%–27% for patients with PD-L1+ tumors and 10%–17% for unselected patients. The phase III ONO-4538-12 (ATTRACTION 2) trial has demonstrated an improved overall survival for nivolumab compared with placebo for patients with heavily pretreated gastric cancer. In the future, we will need better biomarkers to select those most likely to respond and/or identify patients who may need combination immunotherapeutics or alternate strategies. A number of subsets of gastric cancer with different immune signatures, most notably tumors positive for Epstein-Barr virus and microsatellite instability, have been identified, with approximately 50% and 94% PD-L1+ staining seen on tumor cells and immune cells in the EBV subtype and approximately 33% and 45% PD-L1+ staining seen on tumor cells and immune cells in MSI high tumors. Both subtypes demonstrate PD-L1+ immune cells with tumor-infiltrating patterns, unlike the more commonly seen PD-L1+ immune cells at the invasive margin. PD-L2 expression has been reported in 52% of esophageal adenocarcinomas but little is known about the expression of other immune checkpoints. Additional factors that suggest gastroesophageal cancers may respond to checkpoint inhibition include the high somatic mutation burden and the link with chronic inflammation. Here we provide a comprehensive review of the checkpoint inhibitor data published to date in advanced esophagogastric cancers and rationalize how the immune microenvironment in these diverse tumors can explain response or resistance to immunotherapeutics.


PEDIATRICS ◽  
1996 ◽  
Vol 97 (6) ◽  
pp. 949-954
Author(s):  
Alan L. Bisno

Acute pharyngitis may be caused by a wide variety of microbial agents (Table 1). The relative importance of each of these agents varies greatly depending on a number of epidemiologic factors, including age of the patient, season of the year, and geographic locale. Viruses Most cases of acute pharyngitis are viral in etiology and involve the pharynx as well as other portions of the respiratory tract as manifestations of the common cold, influenza, or croup. Examples include the rhinoviruses, coronaviruses, influenza A and B, and the parainfluenza viruses. Certain viral infections causing sore throat may exhibit clinical manifestations that are rather distinctive. Examples include enteroviruses (herpangina due to Coxsackie A), Epstein-Barr virus (infectious mononucleosis), cytomegalovirus (cytomegalovirus mononucleosis), adenovirus (pharyngoconjunctival fever, acute respiratory disease of military recruits), and herpes simplex virus (pharyngitis, gingivitis, and stomatitis). In many instances, however, the illnesses caused by these agents may overlap so broadly with that of streptococcal pharyngitis as to be clinically indistinguishable. Thus, Epstein-Barr virus, adenovirus, and herpes virus may all cause fever, exudative pharyngitis, and cervical adenitis. Several studies have documented the role of primary herpesvirus type 1 infection as a cause of acute pharyngitis in college students.1-4 Herpesvirus type 2 can occasionally cause a similar illness as a consequence of oral-genital sexual contact.5 Although herpesvirus infections may involve the anterior oral cavity (vesicular or ulcerative gingivostomatitis) as well as the posterior pharynx, they do not routinely do so. Only about one-fourth of students with culturally and serologically proven primary herpes simplex type 1 pharyngitis studied by Glezen et al,2 for example, had gingivostomatitis.


2018 ◽  
Vol 8 (3) ◽  
pp. 198-206
Author(s):  
Keita Nakanishi ◽  
Hiroshi Kaito ◽  
Miki Ogi ◽  
Denshi Takai ◽  
Junya Fujimura ◽  
...  

Viral infections in patients with post-kidney transplantation are often difficult to diagnose as well as treat. We herein report three cases with severe viral infections after kidney transplantation. All their causative pathogens could be detected promptly by polymerase chain reaction and flow cytometry during the early stages of infection. These examinations would also be of great use to monitor therapeutic responses and disease activity. It is indeed true that no specific treatment is available for most of the viral infections, but we should be aware that some infections, such as Epstein-Barr virus infection, can be treatable with prompt and specific treatment, such as rituximab.


2020 ◽  
Vol 4 (1) ◽  
pp. e000620 ◽  
Author(s):  
Sadaf Malik ◽  
Tarjei Tørre Asprusten ◽  
Maria Pedersen ◽  
Julie Mangersnes ◽  
Gro Trondalen ◽  
...  

​BackgroundCognitive–behavioural therapy (CBT) is effective in chronic fatigue syndrome. However, CBT has not been investigated in postinfectious chronic fatigue (CF), nor is it known whether addition of therapeutic elements from other disciplines might be feasible. We studied the feasibility of a combined CBT and music therapy intervention for CF following Epstein-Barr virus (EBV) infection in adolescents.​MethodsAdolescents (12–20 years old) participating in a postinfectious cohort study who developed CF 6 months after an acute EBV infection were eligible for the present feasibility study. A combined CBT and music therapy programme (10 therapy sessions and related homework) was compared with care as usual in a randomised controlled design. Therapists and participants were blinded to outcome evaluation. Endpoints included physical activity (steps/day), symptom scores, recovery rate and possible harmful effects, but the study was underpowered regarding efficacy. Total follow-up time was 15 months.​ResultsA total of 43 individuals with postinfectious CF were included (21 intervention group, 22 control group). Seven individuals left the study during the first 3 months, leaving 15 in the intervention group and 21 in the control group at 3 months’ follow-up. No harmful effects were recorded, and compliance with appointment was high. In intention-to-treat analyses, number of steps/day tended to decrease (difference=−1158, 95% CI −2642 to 325), whereas postexertional malaise tended to improve (difference=−0.4, 95% CI −0.9 to 0.1) in the intervention group at 3 months. At 15 months’ follow-up, there was a trend towards higher recovery rate in the intervention group (62% vs 37%).​ConclusionAn intervention study of combined CBT and music therapy in postinfectious CF is feasible, and appears acceptable to the participants. The tendencies towards positive effects on patients’ symptoms and recovery might justify a full-scale clinical trial.​Trial registration numberNCT02499302.


2021 ◽  
Author(s):  
Neeraj Sharma ◽  
Rajat Shukla ◽  
Rachna Warrier ◽  
Kunal Kumar ◽  
Nalin Singh ◽  
...  

Abstract Pancytopenia is a condition when person has low count of all three types of blood cells causing a triage of anemia, leukopenia and thrombocytopenia. It should not be considered as a disease in itself but rather the sign of a disease that needs to be further evaluated. Among the various causes, viral infections like Human Immunodeficiency Virus, Cytomegalovirus, Epstein-Barr virus and Parvovirus B19 have been implicated. Pancytopenia is a rare complication and not commonly seen in patients with COVID 19 disease. Here, we report a case of pancytopenia in previously immunocompetent elderly male patient with SARS-CoV2 infection.


2013 ◽  
Vol 18 (1) ◽  
pp. 7-14
Author(s):  
T. A. Svintsova ◽  
D. M. Sobchak ◽  
O. V. Korochkina ◽  
G. A Kravchenko ◽  
V. V Novikov

The indices of immune response were studied in 68 patients with infectious mononucleosis caused by the Epstein-Barr virus (35 males, 33 females) aged 18 to 30 years. Materials and methods. The content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50, sHLAI, sCD54) has been studied with enzyme immunoassay using monoclonal antibodies Mab IC0-20 and polyclonal antibodies to the antigens of the mononuclear cells of the peripheral blood. The control group included 60 healthy volunteers matched for age and sex with the main group. The aim of this study is the assessment of the content of soluble forms of differentiation antigens in patients with infectious mononucleosis caused by Epstein-Barr virus, depending on gender, age, severity of illness, comorbidities, laboratory values, the presence of viral DNA, as well as a demonstration of their value in predicting the course and outcome of the disease and the efficacy of antiviral and immunocorrecting therapy. In patients with negative results of DNA indication of EBV a significant increase in the content of soluble forms of differentiation antigens characterizing the adhesion of leukocytes (sCD18), the activity of T-lymphocytes (sCD50), the recognition of foreign antigens (sHLAI) in the blood in comparison with patients with a positive DNA indication of EBV was determined. Conclusion. According to the results of this performed work the criterion for an adequate immune response in patients with infectious mononucleosis caused by the Epstein-Barr virus was found to be the increase of the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54). In patients with exanthema, tonsillar syndrome, leukocytosis, elevation of transaminases and the presence of antibodies to capsid antigen (a/VCAIgM) the content of soluble forms of differentiation antigens (sCD95, sCD18, sCD50 sHLAI, sCD54), was higher than in patients without such symptoms. In the treatment with cycloferon in patients with cyclic course of EBV infectious mononucleosis the content of sHLAI and sCD54 at 2nd-4th weeks of treatment increased by 1.5-2 times compared with the corresponding values before treatment. In patients with reactivation of the disease monotonically low indices of all studied soluble forms of differentiation antigens persisted over the 4 weeks during patients following up. In patients with infectious mononucleosis caused by Epstein-Barr virus, the dynamics of sHLAI and sCD54 after 2-4 weeks of treatment serves as secondary efficacy endpoint of antiviral, immunomodulatory therapy and the formation of the cyclic course of the disease.


2012 ◽  
pp. 305-311 ◽  
Author(s):  
María Lilia Diaz Betancourth ◽  
Julio Cesar Klinger ◽  
Victoria Eugenia Niño

Lymphocytopenia and CD4+ T lymphocytopenia can be associated with many bacterial, fungal, parasite and viral infections. They can also be found in autoimmune and neoplastic diseases, common variable immu­nodeficiency syndrome, physical, psychological and traumatic stress, malnutrition and immunosuppressive therapy. Besides, they can also be brought into relation, without a known cause, with idiopathic CD4+ T lym­phocytopenia. Among viral infections, the Retrovirus, specially the human immunodeficiency virus, is the most frequently cause. However, many acute viral infections, including cytomegalovirus and Epstein Barr virus can be associated with transient lymphocytopenia and CD4+ T lymphocytopenia. As is well known, transient lymphocytopenia and CD4+ T lymphocytopenia are temporary and overcome when the disease improves. Nonetheless, severe CD4+ T Lymphocytopenia associated with chronic infections by human herpes virus has not been reported. We describe 6 cases of human immunodeficiency virus negative patients, with chronic cytomegalovirus and Epstein Barr virus infections and profound lymphocytopenia with clinical symptoms of cellular immunodeficiency. These patients improved rapidly with ganciclovir or valganciclovir treatment. We claim here that it is important to consider the chronic human herpes virus infection in the differential diag­nosis of profoundly CD4+ T lymphocytopenia etiology, when human immunodeficiency virus is absent, in order to start effective treatment and to determine, in future studies, the impact of chronic human herpes virus infection in human beings’ health.


Sign in / Sign up

Export Citation Format

Share Document