scholarly journals Effectiveness of treatment of patients with systemic autoimmune diseases on the background of reactivation of persistent Epstein-Barr virus infection

2021 ◽  
Vol 26 (3) ◽  
pp. 47-54
Author(s):  
K.O. Lishchuk-Yakymovych ◽  
I.H. Haiduchok ◽  
K.E. Ischeykin ◽  
V.V. Chopyak
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Study Data ◽  
Immunocompetent Cells ◽  
Epstein Barr Virus Infection ◽  
Inosine Pranobex ◽  
Systemic Autoimmune Diseases ◽  
Suppressor Activity ◽  
Ebv Infection ◽  
Epstein Barr

The article presents the study of effectiveness of inosine pranobex (IP) in patients with systemic autoimmune diseases (SAD) on the background of reactivation of persistent Epstein-Barr (EBV) infection. Among 380 patients with SAD (systemic lupus erythematosus, systemic vasculitides, rheumatoid arthritis, psoriasis), in 144 patients (37.9%) the reactivation of persistent EBV infection was detected through virus DNA identification using polymerase chain reaction (PCR) in three biological matrices (blood, saliva, scraping from the lesion site). 48 patients were receiving inosine pranobex at a dose of 50 mg/kg per day for three months. Treatment efficacy was controlled by studying the levels of expression of miR-146а, miR-155, miR EBV (BART-13 and BART-15), TLR9, the quantity of lymphocytes populations and subpopulations. After treatment, PCR results showed a decrease in viral replication in 66.7% of cases. The use of IP contributed to a significant decrease in the level of IgM, IgG specific antibodies, an increase in the level of expression of anti-inflammatory miR-146a, a decrease in the level of expression of pro-inflammatory miR-155 which may signify the strengthening of antiviral control. The study data demonstrated the decrease in the expression of miR EBV (BART-13 and BART-15) and TLR9 on the immunocompetent cells that can also be attributed to the criteria for IP effectiveness. The effectiveness of IP was also proved by the stabilization of cell mechanisms, namely the tendency to normalizing T and B cell populations, decrease in the number of natural killer cells and activated cells (CD25+, CD3+ HLA DR+). On the other hand, the number of lymphocytes with suppressor activity (CD4+25+) remained significantly high mitigating autoimmune aggression. The results of the study show that the use of IP for treating the acute phase of EBV infection contributed to the decrease of repliсative activity of the virus; suppressing the aggressiveness of autoimmune reactions. The decrease in the expression of miR EBV (BART-13 and BART-15) can be recommended as a criterion for the IP effectiveness; the decrease in the expression of TLR9 on immunocompetent cells –as a criterion for suppressing autoimmune reactions.

scholarly journals CYTOMEGALOVIRUS AND VIRUS EPSTEIN- BARR INFECTION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ITS DEPENDENCE ON GENDER AND AGE OF PATIENTS

World Science ◽  
2020 ◽  
Author(s):  
O. Abrahamovych ◽  
U. Abrahamovych ◽  
S. Guta ◽  
M. Farmaha ◽  
L. Kobak
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Epstein Barr Virus Infection ◽  
Cmv Infection ◽  
Systemic Lupus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr ◽  
Barr Virus Infection

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.  

scholarly journals Epstein-Barr Virus in Systemic Autoimmune Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Anette Holck Draborg ◽  
Karen Duus ◽  
Gunnar Houen
Keyword(s):  
Autoimmune Diseases ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Immune Escape ◽  
Connective Tissue Diseases ◽  
Systemic Autoimmune Diseases ◽  
Barr Virus ◽  
Epstein Barr ◽  
Genetic And Environmental Factors ◽  
Immune Escape Mechanisms

Systemic autoimmune diseases (SADs) are a group of connective tissue diseases with diverse, yet overlapping, symptoms and autoantibody development. The etiology behind SADs is not fully elucidated, but a number of genetic and environmental factors are known to influence the incidence of SADs. Recent findings link dysregulation of Epstein-Barr virus (EBV) with SAD development. EBV causes a persistent infection with a tight latency programme in memory B-cells, which enables evasion of the immune defence. A number of immune escape mechanisms and immune-modulating proteins have been described for EBV. These immune modulating functions make EBV a good candidate for initiation of autoimmune diseases and exacerbation of disease progression. This review focuses on systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Sjögren’s syndrome (SS) and sum up the existing data linking EBV with these diseases including elevated titres of EBV antibodies, reduced T-cell defence against EBV, and elevated EBV viral load. Together, these data suggest that uncontrolled EBV infection can develop diverse autoreactivities in genetic susceptible individuals with different manifestations depending on the genetic background and the site of reactivation.

scholarly journals COMPLAINTS OF THE PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS AND ACTIVE CYTOMEGALOVIRUS AND EPSTEIN-BARR VIRUS INFECTION; THEIR DIAGNOSTIC VALUE

2020 ◽  
Author(s):  
O. Abrahamovych ◽  
U. Abrahamovych ◽  
S. Guta ◽  
O. Synenkyi ◽  
V. Chemes
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Virus Infection ◽  
Lupus Erythematosus ◽  
Epstein Barr Virus ◽  
Diagnostic Value ◽  
Epstein Barr Virus Infection ◽  
Systemic Lupus ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Actuality. The infection with cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in the patients with systemic lupus erythematosus (SLE) is of particular interest to researchers. SLE is a chronic autoimmune disease of unknown etiology that is characterized by multisystemic lesions and is potentially life-threatening [1, 2, 3]. The severity of the problem is caused by the fact that active viral infection can change the manifestations of SLE, but these changes are not always specific, so primary care physicians have no reason to suspect active virus infection at the first stage of examination of SLE patients and prescribe expensive direct virological tests accordingly. It has not been definitively established yet which complaints are the most meaningful regarding the presence of active viral infection in patients with SLE.The purpose of the research was to study complaints in SLE patients with active cytomegalovirus and Epstein-Barr virus infection and determine their diagnostic value. Materials and methods. We randomly enrolled 120 SLE patients – 15 men (12.50%) and 105 women (87.50%) aged 18 to 69 years. All patients received treatment at the Rheumatology Department of Lviv Regional Clinical Hospital in 2014-2019. The diagnosis of SLE was established based on the diagnostic criteria of the American College of Rheumatologists (ACR, 1997). In addition, IgM and IgG antibodies to serum viruses were detected for the diagnosis of CMV and EBV infection. To confirm the presence of active viral infection, viruses were detected in media (CMV - urine, blood; EBV - oral mucosa, blood) by polymerase chain reaction, resulting in 28 patients with SLE (23.33%) detected active CMV infection, in 21 patients with SLE (17.50%) - active EBV infection and in 15 patients with SLE (12.5%) - a combination of active CMV and EBV infection. To achieve the purpose of the study, we identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value. We identified three steps: the first step was to analyze complaints in patients with SLE with active CMV infection and determine their diagnostic value, the second - in the analysis of complaints in patients with SLE with active EBV infection and clarify their diagnostic values and the third - in the analysis of complaints in patients with SLE with a combination of active CMV and EBV infection and clarification of their diagnostic value.Statistical analysis was performed by calculating the chances of establishing the phase of CMV and EBV infection in patients with SLE, using a separate feature - a marker that can be detected during the initial examination of the patient. The probable probability of active infection was determined using indicators of sensitivity, specificity and accuracy [4]. The actual material was processed on a personal computer in MS Excel and SPSS on the basis of conjugation tables with calculation of diagnostic value indicators. The association between active infection and a particular patient complaint was considered to be confirmed when the coefficient of association exceeded 0.5 (or 0.3 for the coefficient of contingency). Research results. It was found that in patients with SLE the presence of active cytomegalovirus infection among the main complaints significantly more often indicate the presence of myalgias (coefficient of association 0.79) or fever (0.51), or chills of the extremities (0.51), or arthralgia (coefficient of contingent 0.31). The presence of active virus Epstein - Barr infections are significantly more often evidenced by the presence of myalgias (coefficient of contingent 0.31) or sleep disorders (coefficient of association 0.84), or mood swings (0.74), or fever (0.61), or the appearance of new rashes (0.53). On the presence of a combination of active cytomegalovirus and virus Epstein - Barr infections significantly more often indicate complaints of sleep disturbances (coefficient of association 0.97) or mood swings (0.83), or a feeling of dryness in the eyes (0.51), or fever (0.50). Conclusions. The presence of active cytomegalovirus infection in patients with systemic lupus erythematosus among the main complaints often indicates the presence of myalgias or fever, or chills of the extremities, or arthralgia, the presence of active virus Epstein - Barr infection - myalgia or sleep disturbances, or mood swings, or fever, or the appearance of new rashes, the presence of their combination - sleep disturbances or mood swings, or a feeling of dryness in the eyes, or fever, which can be used in the diagnostic algorithm. The established patterns of complaints allow us to reasonably suspect in patients with systemic lupus erythematosus the presence of active cytomegalovirus and Epstein-Barr virus infection, the final verification of which requires the use of direct serological tests.

scholarly journals Epstein-Barr Virus and Systemic Autoimmune Diseases

2021 ◽  
Vol 11 ◽  
Author(s):  
Gunnar Houen ◽  
Nicole Hartwig Trier
Keyword(s):  
B Cells ◽  
Epithelial Cells ◽  
Autoimmune Diseases ◽  
Epstein Barr Virus ◽  
Cell Types ◽  
Human Beings ◽  
Systemic Autoimmune Diseases ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

Epstein-Barr Virus (EBV) is an extremely successful human herpes virus, which infects essentially all human beings at some time during their life span. EBV infection and the associated immune response results in production of antibodies (seroconversion), which occurs mainly during the first years of life, but may also happen during adolescence or later in life. Infection of adolescents can result in infectious mononucleosis, an acute serious condition characterized by massive lymphocytosis. Transmission of EBV mainly occurs through saliva but can rarely be spread through semen or blood, e.g. through organ transplantations and blood transfusions. EBV transmission through oral secretions results in infection of epithelial cells of the oropharynx. From the epithelial cells EBV can infect B cells, which are the major reservoir for the virus, but other cell types may also become infected. As a result, EBV can shuttle between different cell types, mainly B cells and epithelial cells. Moreover, since the virus can switch between a latent and a lytic life cycle, EBV has the ability to cause chronic relapsing/reactivating infections. Chronic or recurrent EBV infection of epithelial cells has been linked to systemic lupus erythematosus and Sjögren’s syndrome, whereas chronic/recurrent infection of B cells has been associated with rheumatoid arthritis, multiple sclerosis and other diseases. Accordingly, since EBV can shuttle between epithelial cells and B cells, the systemic autoimmune diseases often occur as overlapping syndromes with symptoms and characteristic autoantibodies (e.g. antinuclear antibodies and rheumatoid factors) reflecting epithelial and/or B cell infection.

scholarly journals DNA Damage Response and Oxidative Stress in Systemic Autoimmunity

2019 ◽  
Vol 21 (1) ◽  
pp. 55 ◽  
Author(s):  
Vassilis L. Souliotis ◽  
Nikolaos I. Vlachogiannis ◽  
Maria Pappa ◽  
Alexandra Argyriou ◽  
Panagiotis A. Ntouros ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Dna Damage ◽  
Autoimmune Diseases ◽  
Dna Damage Response ◽  
Lupus Erythematosus ◽  
Mononuclear Cells ◽  
Tissue Injury ◽  
Systemic Autoimmune Diseases ◽  
Damage Response

The DNA damage response and repair (DDR/R) network, a sum of hierarchically structured signaling pathways that recognize and repair DNA damage, and the immune response to endogenous and/or exogenous threats, act synergistically to enhance cellular defense. On the other hand, a deregulated interplay between these systems underlines inflammatory diseases including malignancies and chronic systemic autoimmune diseases, such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Patients with these diseases are characterized by aberrant immune response to self-antigens with widespread production of autoantibodies and multiple-tissue injury, as well as by the presence of increased oxidative stress. Recent data demonstrate accumulation of endogenous DNA damage in peripheral blood mononuclear cells from these patients, which is related to (a) augmented DNA damage formation, at least partly due to the induction of oxidative stress, and (b) epigenetically regulated functional abnormalities of fundamental DNA repair mechanisms. Because endogenous DNA damage accumulation has serious consequences for cellular health, including genomic instability and enhancement of an aberrant immune response, these results can be exploited for understanding pathogenesis and progression of systemic autoimmune diseases, as well as for the development of new treatments.

scholarly journals Acute Acalculous Cholecystitis: A Rare Presentation of Primary Epstein-Barr Virus Infection in Adults—Case Report and Review of the Literature

2017 ◽  
Vol 2017 ◽  
pp. 1-5 ◽  
Author(s):  
Zuhal Yesilbag ◽  
Asli Karadeniz ◽  
Fatih Oner Kaya
Keyword(s):  
Epstein Barr Virus ◽  
Conservative Therapy ◽  
Gastrointestinal Symptoms ◽  
Acalculous Cholecystitis ◽  
Acute Acalculous Cholecystitis ◽  
Epstein Barr Virus Infection ◽  
Rare Presentation ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

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.

scholarly journals Leucine-Rich Glioma-Inactivated Protein 1 Antibody-Positive Polyradiculopathy Associated with Epstein-Barr Virus Infection

2021 ◽  
pp. 549-554
Author(s):  
Berrin Pelit Uzunalimoğlu ◽  
Abdülhamit Sağlam ◽  
Büşra Şişman ◽  
Sefer Günaydın ◽  
Esen Gül Uzuner ◽  
...  
Keyword(s):  
Lymph Node ◽  
Motor Neurons ◽  
Epstein Barr Virus ◽  
Whole Body ◽  
Reactive Lymphoid Hyperplasia ◽  
Epstein Barr Virus Infection ◽  
Barr Virus ◽  
Ebv Infection ◽  
Cell Counts ◽  
Epstein Barr

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.

scholarly journals Tocilizumab for the Treatment of Rheumatoid Arthritis and Other Systemic Autoimmune Diseases: Current Perspectives and Future Directions

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Atsushi Ogata ◽  
Toshio Tanaka
Keyword(s):  
Rheumatoid Arthritis ◽  
Autoimmune Diseases ◽  
Host Defense ◽  
Lupus Erythematosus ◽  
Therapeutic Strategy ◽  
Case Reports ◽  
Systemic Autoimmune Diseases ◽  
Future Directions ◽  
Pilot Studies ◽  
Beneficial Effects

Interleukin (IL)-6 is a cytokine featuring redundancy and pleiotropic activity. While IL-6, when transiently produced, contributes to host defense against acute environmental stress, continuous dysregulated IL-6 production plays a significant pathological role in several systemic autoimmune diseases. In response to the expectation that IL-6 blockade would constitute a novel therapeutic strategy for the treatment of these diseases, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Clinical trials have verified the efficacy and the safety of tocilizumab for patients with rheumatoid arthritis, resulting in approval of this innovative biologic for the treatment of rheumatoid arthritis in more than 90 countries worldwide. Pathological analyses of the effect of IL-6 on the development of autoimmune diseases and a considerable number of case reports and pilot studies have also indicated the beneficial effects of this antibody on other systemic autoimmune diseases, including systemic lupus erythematosus, systemic sclerosis, polymyositis, and large-vessel vasculitis.

Transient Immunodeficiency During Asymptomatic Epstein-Barr Virus Infection

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 964-967
Author(s):  
THOMAS J. BOWEN ◽  
RALPH J. WEDGWOOD ◽  
HANS D. OCHS ◽  
WERNER HENLE
Keyword(s):  
Epstein Barr Virus ◽  
Mononuclear Cells ◽  
Epstein Barr Virus Infection ◽  
Peripheral Blood Mononuclear ◽  
Immunoglobulin Synthesis ◽  
Barr Virus ◽  
Ebv Infection ◽  
Epstein Barr

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.

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