Epstein–Barr virus, cytomegalovirus and BK polyomavirus burden in juvenile systemic lupus erythematosus: correlation with clinical and laboratory indices of disease activity

Objectives Clinical and laboratory investigations have revealed that Epstein–Barr virus (EBV) is involved in altered immunological response of systemic lupus erythematosus (SLE). Higher seroprevalence rates of anti-EBV antibodies and increased viral load are demonstrated in adult SLE patients. The prevalence of BK polyomavirus (BKV) reactivation is also suggested to be higher in SLE. Herein, we aimed to evaluate the immune response of children with SLE to EBV antigens in addition to EBV and BKV DNA. We also tried to evaluate whether these serological results differ from another connective tissue disease – juvenile systemic sclerosis (jSS) – and healthy individuals. Methods Serum levels of EBV early antigen diffuse (EA-D) IgG, EBV nuclear antigen-1 IgG, EBV viral capsid antigen (VCA), cytomegalovirus (CMV) IgG, EBV DNA, CMV DNA and urinary BKV DNA were evaluated in healthy controls and in patients with a diagnosis of juvenile SLE (jSLE) and jSS. Results A total of 70 jSLE patients, 14 jSS patients and 44 sex-matched healthy individuals were involved in the study. EBV VCA was positive in 84.2% of jSLE patients, 85.7% of jSS patients and 36.3% of healthy controls. EBV EA-D IgG positivity was significantly higher in jSLE patients compared to jSS patients and healthy controls (20% vs. 7.1% and 0%, p = 0.005). EBV VCA positivity was associated with malar rash and immunological disorder, but there was no statistical significance in other antibody positivity in terms of clinical and haemogram findings and autoantibody positivity. CMV DNA positivity was present in only 2.8% of jSLE patients. None of the jSS patients or the healthy controls had CMV DNA positivity. EBV DNA and BKV DNA were also negative in all three groups. Conclusion The results of our study assume a relationship between SLE and EBV, but we could not demonstrate an association between CMV and BKV. The negative DNA results in contrast to serological positivity can be interpreted as an altered and impaired immune system and increased viral susceptibility. These results suggest that EBV contributes to disease continuity, even if it does not directly cause development.

Download Full-text

FRI0157 EPSTEIN BARR VIRUS BLOOD REPLICATION INCREASES DURING ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.734 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 662.3-662

Author(s):

P. Breillat ◽

A. Mathian ◽

S. Burrel ◽

M. Hié ◽

J. Fadlallah ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Viral Load ◽

Disease Activity ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Systemic Lupus ◽

Sledai Score ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

Background:A role for Epstein Barr Virus (EBV) infection in Systemic Lupus Erythematosus (SLE) pathogenesis is highly suspected. The frequency of EBV seroprevalence and DNA detection in peripheral blood mononuclear cells are increased in SLE patients compared to healthy controls.Objectives:To analyse the relationship between EBV blood replication and SLE disease activity.Methods:Monocentric, observational and retrospective study of SLE patients (ACR or SLICC criteria) who have had a blood EBV DNA assessment using Polymerase Chain Reaction (artus® EBV Virus QS-RGQ assay) between 2012 and 2018. Exclusion criteria were: organ or bone marrow transplant, absence of EBV seroconversion and insufficient data. SLE clinical features, the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) flare index (SFI) and therapeutic regimen on the day of EBV DNA load assessment were recorded. A SELENA-SLEDAI score > 4 defined an active SLE. A blood EBV DNA load ≥125 IU/mL was defined as elevated.Results:A total of 105 patients (98 women and 7 men) were included in the study. At inclusion, median (quartiles) age and SLE duration were 34 (23.5-43) and 7 (2-14) years old, respectively. Treatment were hydroxychloroquine (HCQ) (n = 67; 64%), prednisone (n = 66; 63%) with an average (±Standard Deviation) dose of 11.3 (±16) mg/day and an immunosuppressant (n = 42; 40%). According to SFI, 57 SLE patients were experiencing a flare at the time of EBV assessment; flares were classified as severe and mild/moderate in 38 (36%) and 19 (18%) SLE patients, respectively. According to the SELENA-SLEDAI score, 60 patients (57%) were deemed active and 45 (43%) inactive. Main clinical manifestations were arthritis in 32 (30%) patients, constitutional symptoms (fever, weight loss, anorexia or lymphadenopathy) in 31 (30%), cutaneous involvement in 23 (22%), glomerulonephritis in 19 (18%), cytopenia in 14 (13%), neuropsychiatric involvement in 13 (12%) and serositis in 10 (16%). Blood EBV DNA was elevated in 54 (90%) of the 60 patients with active lupus versus 6 (13%) of the 45 patients with inactive SLE (p <10-4). It was increased in 34 (89%) of the 38 patients with severe flare, in 17 (89%) of the 19 patients with a mild/moderate flare (p = 1) and in 8 (17%) of the 48 patients without flare (p <10-4vs severe flare and p <10-4vs mild/moderate flare). EBV DNA load correlated with SELENA-SLEDAI score (r=0.58; p<0.0001). Elevated blood EBV DNA was not associated with HCQ, prednisone or immunosuppressant intakes. Eighteen patients with active SLE had a second assessment of blood EBV DNA load. For these patients, the median [range] of viral load was significantly higher during periods of active SLE (236 [0-2680] IU/mL) compared with periods with lower SELENA-SLEDAI score (0 [0-1537] IU/mL, p<10-4in paired analysis).Conclusion:Blood EBV viral load is dramatically increased in active phase of SLE, independently of the treatment. We were unable to demonstrate whether the replication of EBV was the cause or the consequence or just an epiphenomenon of the disease activity. Further studies are needed to study whether EBV viral load is linked with Interferons secretion or B lymphocyte activation.Disclosure of Interests:None declared

Download Full-text

Epstein–Barr Virus in Salivary Samples from Systemic Lupus Erythematosus Patients with Oral Lesions

Journal of Clinical Medicine ◽

10.3390/jcm10214995 ◽

2021 ◽

Vol 10 (21) ◽

pp. 4995

Author(s):

Alessio Buonavoglia ◽

Patrizia Leone ◽

Marcella Prete ◽

Antonio Giovanni Solimando ◽

Chiara Guastadisegno ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Oral Lesions ◽

Systemic Lupus ◽

Real Time Quantitative Pcr ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

In order to investigate the possible role of Epstein–Barr virus (EBV) in systemic lupus erythematosus (SLE) and its associated oral lesions, a pilot case–control study was performed. A total of 31 patients (18 females and 13 males) were enrolled in the study and divided into two groups: group A included 16 patients with diagnosis of SLE and group B included 15 healthy individuals. Salivary swab samples were collected and subjected to molecular screening by real-time quantitative PCR (qPCR) for the detection of EBV DNA. EBV DNA was significantly detected in 8/16 (50%) SLE patients and in 5/7 (71.4%) subjects with SLE-associated oral lesions. Since EBV is one of the most common viruses in the human population, it is difficult to understand if it is the causative agent of SLE or, vice versa, if SLE is able to trigger the reactivation of EBV. This study highlights a significant association between the presence of EBV and both SLE and SLE-related oral lesions and provides rationale for further investigation into the role of EBV in SLE pathogenesis.

Download Full-text

EBNA1 IgM-Based Discrimination Between Rheumatoid Arthritis Patients, Systemic Lupus Erythematosus Patients and Healthy Controls

Antibodies ◽

10.3390/antib8020035 ◽

2019 ◽

Vol 8 (2) ◽

pp. 35 ◽

Cited By ~ 1

Author(s):

Nicole Hartwig Trier ◽

Anette Holck Draborg ◽

Louise Sternbæk ◽

Lone Troelsen ◽

Janni Lisander Larsen ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Connective Tissue Diseases ◽

Nuclear Antigen ◽

Healthy Controls ◽

Systemic Lupus ◽

Barr Virus ◽

Epstein Barr

Epstein–Barr Virus (EBV) has been associated with development of rheumatic connective tissue diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) in genetically susceptible individuals. Diagnosis of RA and SLE relies on clinical criteria in combination with the presence of characteristic autoantibodies. In addition, antibodies to several EBV antigens have been shown to be elevated in patients with these diseases compared to healthy controls (HC). Here, we elaborated improved enzyme-linked immunosorbent assays for antibodies (IgM, IgA, IgG) to the EBV proteins Epstein-Barr Virus nuclear antigen (EBNA)1 and early antigen diffuse (EAD) in order to determine their potential diagnostic role. We showed that especially EBNA1 IgM distinguished RA from SLE and HCs and also distinguished SLE from HCs. EBNA1 IgA was almost as effective in differentiating RA from SLE and HC, while EAD IgG and IgA were able to discern SLE patients from RA patients and HCs. Collectively, these findings illustrate the potential diagnostic use of antibodies to EBV proteins to diagnose RA and to differentiate SLE from RA.

Download Full-text

Elevated Concentrations of Serum Immunoglobulin Free Light Chains in Systemic Lupus Erythematosus Patients in Relation to Disease Activity, Inflammatory Status, B Cell Activity and Epstein-Barr Virus Antibodies

PLoS ONE ◽

10.1371/journal.pone.0138753 ◽

2015 ◽

Vol 10 (9) ◽

pp. e0138753 ◽

Cited By ~ 13

Author(s):

Anette H. Draborg ◽

Magnus C. Lydolph ◽

Marie Westergaard ◽

Severin Olesen Larsen ◽

Christoffer T. Nielsen ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Cell Activity ◽

Light Chains ◽

Systemic Lupus ◽

Free Light Chains ◽

Barr Virus ◽

Inflammatory Status ◽

Epstein Barr

Download Full-text

Association of Epstein-Barr virus with systemic lupus erythematosus: Effect modification by race, age, and cytotoxic T lymphocyte-associated antigen 4 genotype

Arthritis & Rheumatism ◽

10.1002/art.20997 ◽

2005 ◽

Vol 52 (4) ◽

pp. 1148-1159 ◽

Cited By ~ 66

Author(s):

Christine G. Parks ◽

Glinda S. Cooper ◽

Lori L. Hudson ◽

Mary Anne Dooley ◽

Edward L. Treadwell ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Lymphocyte ◽

Lupus Erythematosus ◽

Epstein Barr Virus ◽

Cytotoxic T Lymphocyte ◽

Effect Modification ◽

Systemic Lupus ◽

Barr Virus ◽

Epstein Barr

Download Full-text

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

World Science ◽

10.31435/rsglobal_ws/31102020/7225 ◽

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.

Download Full-text