Epstein–Barr virus infection in primary immunodeficiency

2018 ◽  
Vol 5 (3) ◽  
pp. 65-85 ◽  
Author(s):  
Adi Ovadia ◽  
Ilan Dalal

Primary immunodeficiency (PID) is a group of genetic disorders which affects immune cell development, differentiation, and function. The affected individuals are highly susceptible to infection by a diverse array of pathogens. Epstein–Barr virus (EBV) infection is ubiquitous in humans and usually involves an asymptomatic or self-limiting clinical course. In rare cases, EBV can cause not only an acute infection but also a severe exaggerated immune response and lymphoproliferative disease. Furthermore, EBV infection in patients with PID can lead to immune dysregulation and increased risk of malignancies, in addition to the severe course of the acute infection. Recognition of the different genetic defects and their effect on immunological pathways provide us with fundamental insights into the pathophysiology of EBV infection and associated disease, and may lead to developing better targeted therapies in the future. Here, we review all of PIDs with an abnormal response to EBV disease. Statement of novelty: Here we provide a review of the current knowledge of all PIDs reported to be associated with abnormal response to EBV infection and associated disease, such as hemophagocytic lymphohistiocytosis.

2019 ◽  
Vol 12 (7) ◽  
pp. e229615 ◽  
Author(s):  
Haoran Peng ◽  
Tanna Lim ◽  
Jae Nam ◽  
Jin Lee

Epstein-Barr virus (EBV) infections frequently affect the liver and cause hepatitis. EBV is a well-known trigger of certain autoimmune diseases. There are few case reports showing the evidence of autoimmune hepatitis (AIH) following EBV infection. However, the diagnosis of AIH is very challenging in the setting of an acute infection. Here, we demonstrate a case of AIH following EBV infection in a patient ultimately recovered after receiving treatment for AIH.


2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Zuhal Yesilbag ◽  
Asli Karadeniz ◽  
Fatih Oner Kaya

Primary Epstein-Barr virus (EBV) infection is almost always a self-limited disease characterized by sore throat, fever, and lymphadenopathy. Hepatic involvement is usually characterized by mild elevations of aminotransferases and resolves spontaneously. Although isolated gallbladder wall thickness has been reported in these patients, acute acalculous cholecystitis is an atypical presentation of primary EBV infection. We presented a young women admitted with a 10-day history of fever, nausea, malaise who had jaundice and right upper quadrant tenderness on the physical examination. Based on diagnostic laboratory tests and abdominal ultrasonographic findings, cholestasis and acute acalculous cholecystitis were diagnosed. Serology performed for EBV revealed the acute EBV infection. Symptoms and clinical course gradually improved with the conservative therapy, and at the 1-month follow-up laboratory findings were normal. We reviewed 16 adult cases with EBV-associated AAC in the literature. Classic symptoms of EBV infection were not predominant and all cases experienced gastrointestinal symptoms. Only one patient underwent surgery and all other patients recovered with conservative therapy. The development of AAC should be kept in mind in patients with cholestatic hepatitis due to EBV infection to avoid unnecessary surgical therapy and overuse of antibiotics.


Author(s):  
O. Abrahamovych ◽  
U. Abrahamovych ◽  
S. Guta ◽  
M. Farmaha ◽  
L. Kobak

Introduction. Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by various manifestations and clinical course, many aspects of the etiology and pathogenesis of which remain unclear. Recently, the interest of researchers in studying the role of cytomegalovirus (CMV) and Epstein - Barr virus (EBV) has been growing in the occurrence and course of a number of human diseases due to their ability to affect almost all organs and systems of the body, causing the formation of latent, active or chronic infection, which can often cause temporary disability, disability or even death, however, for the patients with SLE, despite the possibility of approaching the difficult problem of diagnosis and treatment of this disease, this issue is given insufficient attention, as evidenced by isolated studies.The aim of the study. Detect cytomegalovirus and Epstein - Barr infection in patients with systemic lupus erythematosus and its dependence on gender and age of patients. Materials and methods of research. The study involved 120 patients (15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years with SLE, who were in the rheumatology department of the Communal Non-Commercial Enterprise of the Lviv Regional Council "Lviv Regional Clinical Hospital" in 2014-2019. To diagnose CMV and EBV infection by enzyme-linked immunosorbent assay, antibodies of IgM and IgG to viruses were detected in blood serum, and viruses were detected by polymerase chain reaction. According to the results of virus detection, formed groups of the patients, namely: patients with active CMV infection, active EBV, active CMV and EBV, without active CMV and EBV. All patients with SLE included in the study were subsequently stratified by age according to the classification of the World Health Organization (2015), according to which the following age limits were determined: young age, middle-aged, elderly, senile. Statistical analysis was performed on a personal computer in MS Excel and Statistica 6.0 using descriptive statistics. The frequency of cases of active CMV and EBV infection was calculated mathematically by the binomial coefficient of I. Newton. Research results and their discussion. We found in the vast majority of patients with SLE (117 patients, 97.50%) increase in the titer of specific antibodies to CMV. Only in 3 patients (2.50%) the titer of antibodies to this virus was within normal limits. Analyzing the frequency of EBV infection in patients with SLE, we recorded an increase in the titer of specific antibodies to the virus in 119 patients (99.17%). Among the examined patients with SLE in all (100.00%) found an increase in the titer of antibodies to CMV and / or EBV, of which 97.50% - infected with CMV and 97.17% - infected with EBV. The active phase of CMV and / or EBV infection was detected in 54.17%, of which 23.33% - active CMV infection, 17.50% - active EBV infection and 12.50% - a combination of active CMV and EBV infection simultaneously, which indicates a high frequency of CMV and EBV infection in patients with SLE and reflects the urgency of the problem of diagnosing herpesvirus infection in them. We found that activeCMV, EBV infections and their combinations are present only in women (64 patients, which is 60.96% of the total number of women with SLE), of which 28 patients (26.67%) there was only active CMV infection, in 21 patients (20.00%) - only active EBV infection and in 15 patients (14.29%) – combination of active CMV and EBV infection. 41 women (39.05%) and all (100.00%) men were not found to have active CMV and EBV infection, which indicates that men at the time of the survey were significantly more likely to have this infection in the integration phase. The most frequently active EBV infection was detected in patients with SLE of young age (17 cases, 24.64%), and in middle-aged patients 3 cases (6.52%) were recorded, which indicates a significant (p <0.05) difference in the frequency of cases of active EBV infection in patients of both groups. Only 1 case (20.00%) of active EBV infection was detected in elderly patients. Conclusions. All patients with systemic lupus erythematosus are infected - 97.50% with cytomegalovirus and 97.17% with Epstein-Barr virus infection, that was confirmed by the increased titer of antibodies to them. Among the mentioned patients 53.33% of them had the active phase of infection (23.33% - cytomegalovirus infection in the replication phase, 17.50% - the Epstein- Barr virus infection in the replication phase and 12.50% - their combination). The prevalence of active viral infection in patients with systemic lupus erythematosus depends on gender (active cytomegalovirus, active Epstein-Barr virus infection and their combination are significantly more common in women) and age - they are probably more common in young patients.  


2021 ◽  
pp. 549-554
Author(s):  
Berrin Pelit Uzunalimoğlu ◽  
Abdülhamit Sağlam ◽  
Büşra Şişman ◽  
Sefer Günaydın ◽  
Esen Gül Uzuner ◽  
...  

Epstein-Barr virus (EBV) has been associated with a plethora of neurological manifestations including polyneuropathy and polyradiculopathy. A 27-year-old man with a recent upper respiratory system infection presented with difficulty in walking. His neurological examination revealed reduced muscle strength in both proximal and distal lower limb muscles without sensory and autonomic signs. Needle electromyography showed abnormal spontaneous activity and reduced recruitment of motor units in muscles innervated by multiple lumbo-sacral roots. Cerebrospinal examination showed increased protein levels with normal cell counts. While spinal MRI was normal, whole-body CT and PET examination showed disseminated lymph node enlargement. Anti-EBV viral capsid antigen and anti-nuclear antigen IgG but not IgM was positive, whereas EBV PCR was negative in blood. Analysis of inguinal lymph node biopsy showed reactive lymphoid hyperplasia and EBV DNA. Leucine-rich glioma-inactivated protein 1 (LGI1) antibody was found in serum but not in CSF. All clinical, imaging, and electrophysiological findings improved following steroid and intravenous immunoglobulin treatment. These findings suggested the acute involvement of lumbo-sacral spinal roots and/or motor neurons. Purely motor polyradiculopathy has been reported in both EBV-positive and LGI1 antibody-positive patients, and EBV infection is known to precede different autoimmune manifestations. Whether EBV infection may trigger LGI1 autoimmunity and cause involvement of spinal motor roots and/or motor neurons needs to be further studied.


PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 964-967
Author(s):  
THOMAS J. BOWEN ◽  
RALPH J. WEDGWOOD ◽  
HANS D. OCHS ◽  
WERNER HENLE

In vivo and in vitro humoral and cellular immune responses were studied in a 2½-year-old girl immediately before, during, and after an asymptomatic infection with Epstein-Barr virus. During the acute EBV infection, the patient's peripheral blood mononuclear cells were deficient in immunoglobulin synthesis and suppressed the in vitro immunoglobulin synthesis of normal allogeneic cells. In vitro mitogen transformation of lymphocytes was reduced. In vivo antibody responses to the T cell-dependent antigens bacteriophage φX 174 and Keyhole limpet hemocyanin were markedly depressed. These studies suggest that suppressor cells induced during acute EBV infection not only suppress immunoglobulin synthesis in vitro, but also interfere with in vivo antibody synthesis.


Blood ◽  
1991 ◽  
Vol 77 (5) ◽  
pp. 1092-1095 ◽  
Author(s):  
A Neri ◽  
F Barriga ◽  
G Inghirami ◽  
DM Knowles ◽  
J Neequaye ◽  
...  

Abstract The Epstein-Barr virus (EBV) is associated with distinct forms of human lymphoid malignancies, including the endemic (eBL) and sporadic forms of Burkitt's lymphoma (sBL) and acquired immunodeficiency syndrome- associated non-Hodgkin lymphoma (AIDS-NHL). However, whether EBV has a pathogenetic role in these tumors or is a passenger virus has not been conclusively demonstrated. One element to distinguish between these two possibilities is to determine whether EBV infection has preceded and, thus, possibly contributed to clonal expansion, or whether infection has occurred after clonal expansion and thus is unlikely to contribute to pathogenesis. Toward this end we analyzed the structure of the heterogeneous genomic termini of EBV as markers of clonal infection in a panel of eBL (11 cases), sBL (9 cases), and AIDS-NHL (10 cases) biopsies. We show that EBV termini are uniformly clonal in sBL, eBL, and AIDS-NHL, strongly suggesting that EBV infection has preceded and, thus, most likely contributed to clonal expansion in these malignancies.


Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2722
Author(s):  
Fenggang Yu ◽  
Yanan Lu ◽  
Yingying Li ◽  
Yuji Uchio ◽  
Utomo Andi Pangnguriseng ◽  
...  

Epstein–Barr virus (EBV) is a human oncogenic virus that causes several types of tumor, such as Burkitt’s lymphoma and nasopharyngeal carcinoma (NPC). NPC tumor cells are clonal expansions of latently EBV-infected epithelial cells. However, the mechanisms by which EBV transforms the nasopharyngeal epithelium is hampered, because of the lack of good in vitro model to pursue oncogenic process. Our primary nasopharyngeal epithelial cell cultures developed pseudostratified epithelium at the air-liquid interface, which was susceptible to EBV infection. Using the highly sensitive RNA in situ hybridization technique, we detected viral infection in diverse cell types, including ciliated cells, goblet cells, and basal cells. EBV-encoded small RNA-positive cells were more frequently detected in the suprabasal layer than in the basal layer. We established the most physiologically relevant EBV infection model of nasopharyngeal epithelial cells. This model will advance our understanding of EBV pathogenesis in the development of NPC.


2017 ◽  
Vol 145 (16) ◽  
pp. 3405-3412 ◽  
Author(s):  
V. GARES ◽  
L. PANICO ◽  
R. CASTAGNE ◽  
C. DELPIERRE ◽  
M. KELLY-IRVING

SUMMARYEpstein-Barr virus (EBV) is a highly prevalent herpesvirus linked to infectious mononucleosis and several malignancies. This paper aims to study the association between children's early life social environment at 9 months and EBV infection at 3 years of age.MethodsWe used data on children included in the UK Millennium Cohort Study. We described the social environment using area-level and material factors as well as socioeconomic position (SEP) at 9 months. EBV was measured at 3 years of age (n = 12 457).ResultsLower rates of EBV infection were observed in children living in towns and rural areas compared with those living in cities. Lower SEP and overcrowding in the household increased the odds of being infected. Children whose parents were social tenants were more likely to be infected than homeowners. In the overall model, the strength of the association between material factors and EBV infection weakened.ConclusionsWe showed that early life material deprivation was associated with a higher risk of EBV infection among 3-year-olds. Children living in more deprived social conditions may be more likely to become EBV carriers at an earlier age.


1994 ◽  
Vol 180 (5) ◽  
pp. 1995-1998 ◽  
Author(s):  
K Ritter ◽  
R J Kühl ◽  
F Semrau ◽  
H Eiffert ◽  
H D Kratzin ◽  
...  

Antibodies directed against the autoantigen p26 were detected in sera from 32 patients with acute Epstein-Barr virus (EBV) infection and clinical symptoms of infectious mononucleosis. P26 has now been identified as the enzyme manganese superoxide dismutase (MnSOD) by comparison of the NH2-terminal amino acid sequence. Antibodies against MnSOD belong to the immunoglobulin class M. They are not detectable in sera of patients with other herpesvirus infections. In the 32 patients investigated, the rise and fall of the autoantibodies coincides with the clinical symptoms. In vitro, the autoantibodies were shown to inhibit the dismutation of superoxide radicals by blocking MnSOD. As presented in the discussion this effect may contribute to the pathogenesis of acute EBV infection.


2016 ◽  
Vol 70 (2) ◽  
pp. 120-125 ◽  
Author(s):  
Mohamed E Ateyah ◽  
Mona E Hashem ◽  
Mohamed Abdelsalam

ObjectiveAcute B lymphoblastic leukaemia (B-ALL) is the most common type of childhood malignancy worldwide but little is known of its origin. Recently, many studies showed both a high incidence of Epstein–Barr virus (EBV) infection and high levels of CD4+CD25+Foxp3+(Treg cells) in children with B-ALL. In our study, we investigated the possible relationship between EBV infection and the onset of B-ALL, and its relation to expression of CD4+, CD25high+Foxp3+ T regulatory cells.Subject and methodsWe analysed expression and mean fluorescence intensity (MFI) of Treg cells in peripheral blood of 45 children with B-ALL and in 40 apparently healthy children as a control, using flow cytometry. Serum anti-EBV viral capsid antigen (VCA) IgG, anti-EBV nuclear antigen (EBNA) IgG (for latent infection) and anti-EBV VCA IgM (for acute infection) were investigated using ELISA.ResultsAnalysis of the Treg cells population in patients and controls revealed that expression of CD4+ CD25high+ T lymphocytes was higher in patients than in controls (mean±SD 15.7±4.1 and 10.61±2.6 in patients and controls, respectively, and MFI of Foxp3 was 30.1±7.1 and 16.7±3.7 in patients and controls, respectively (p<0.001)). There was a high incidence of latent EBV infection in patients (31%) compared with controls (10%) while the incidence of acute infection was 12% in patients and 0% in the control group. To study the role of latent EBV infection in the pathogenesis of acute B-ALL, OR was calculated (OR=4.06, coefficient index 1.2–13.6).ConclusionsThese findings suggest a possible role for Treg cells and EBV in the pathogenesis of B-ALL. Further studies are needed on the possible mechanisms of tumour genesis related to Treg cells and EBV in children with B-ALL.


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