Viral Capsid Antigen Research Articles

EBV Serology and Plasma EBV DNA Load as a Combined Tool for Nasopharyngeal Carcinoma (NPC) Diagnosis and Monitoring in Non-Endemic Regions

There is limited information regarding the clinical significance of Epstein-Barr virus (EBV) markers for nasopharyngeal carcinoma (NPC) diagnoses and monitoring in non-endemic areas. Low NPC incidence in non-endemic countries made it difficult to form a representative group of patients for research this issue. Moreover, NPC cases are often characterized into morphologically different tumor types based upon the geographic and ethnic variability. Since viral and serological markers reflect the different biological events accompanying the development of NPC, it is important to compare their clinical value in the context of different disease manifestations. The implementation of such a study in a non-endemic region is of particular interest, allowing the investigation of the potential impact of differences in the genetic and ethnic characteristics of the population, versus those in populations from endemic regions. In present study, we analyzed clinical significance of two EBV markers (serological and molecular) in large group (96 cases) of undifferentiated non-keratinizing carcinoma of nasopharyngeal type (UNPC) Russian patients. It has been shown that IgA/ VCA antibody titers elevated on patient's admission and being valuable markers for primary UNPC diagnosis do not allow to adequately assessing patients’ state after the treatment. In contrast to EBV serology, the plasma EBV DNA load was found to be valuable marker for clinical evaluation of UNPC patient’s state, such as remission and relapse. It was also shown that the concentration of viral DNA correlated with the UNPC patients' overall survival. The proposed study, conducted on UNPC patients from a non-endemic region, for the first time revealed a direct correlation between IgG/IgA antibody titers to EBV virus capsid antigen (VCA) and the levels of plasma EBV DNA load, and the absence of such correlation between plasma EBV DNA burden and serological responses to EBV. It has also been demonstrated that the combined assessment of plasma EBV DNA load and EBV-specific antibody titers provides a reliable approach to UNPC diagnosis, disease monitoring, and therapeutic response assessment.

FcγRIIb Expression Is Decreased on Naive and Marginal Zone-Like B Cells From Females With Multiple Sclerosis.

B cells are critical to the development of multiple sclerosis (MS), but the mechanisms by which they contribute to the disease are poorly defined. We hypothesised that the expression of CD32b (FcγRIIb), a receptor for the Fc region of IgG with inhibitory activities in B cells, is lower on B cell subsets from people with clinically isolated syndrome (CIS) or MS. CD32b expression was highest on post-naive IgM+ B cell subsets in healthy controls. For females with MS or CIS, significantly lower CD32b expression was identified on IgM+ B cell subsets, including naive and IgMhi MZ-like B cells, when compared with control females. Lower CD32b expression on these B cell subsets was associated with detectable anti-Epstein Barr Virus viral capsid antigen IgM antibodies, and higher serum levels of B cell activating factor. To investigate the effects of lower CD32b expression, B cells were polyclonally activated in the presence of IgG immune complexes, with or without a CD32b blocking antibody, and the expression of TNF and IL-10 in B cell subsets was assessed. The reduction of TNF but not IL-10 expression in controls mediated by IgG immune complexes was reversed by CD32b blockade in naive and IgMhi MZ-like B cells only. However, no consequence of lower CD32b expression on these cells from females with CIS or MS was detected. Our findings highlight a potential role for naive and marginal zone-like B cells in the immunopathogenesis of MS in females, which requires further investigation.

A three year Seroepidemiological and molecular study of Epstein -Barr virus infection among different age groups with hematological malignancies in a Tertiary care centre of North India ( 2017 -2019).

Purpose:Epstein-Barr virus (EBV) is a member of the family Gamma Herpes viridae and is usually implicated in malignancies like non-Hodgkin's lymphoma, Hodgkin's lymphoma and Burkitt's lymphoma. The present study was designed with the aim to estimate the seroprevalence of EBV in people with hematological malignancies and further follow up was planned by viral load quantitation by Real time PCR in positive cases.Methods:The current study was planned for a period of three years and a total of 272 serum samples were tested from patients with hematological malignancies namely; HL, NHL, ALL, CLL. Serological testing was performed for the presence of IgM and IgG antibodies against EBV viral capsid antigen. Sera of the patients found positive for IgM was further subjected to viral DNA extraction and Real Time Quantitative PCR was performed by a commercial kit.Results:The overall seropositivity rate was 89.2% for EBV IgG antibodies and 56.1% for IgM antibodies. The seroprevalence for anti-EBV VCA IgM was found to be highest in the age group <10 years (34.8%) and 11–22 years (20.4%). Of the 109 EBV positive strains by PCR, 27.3% were HL, 35.2% NHL, 24.3% ALL and 13.7% were CLL. The mean viral load was 68.7 × 107 copies/ml DNA.Conclusion:Our study showed a higher seroprevalence and a definite causal relationship of EBV in lymphoma patients. Young adults showed a higher risk of hematological malignancies as compared to elder population. This study can prove to be an essential guide and aid to the primary care physicians in identifying the possible risk factors and seroprevalence in various age groups of EBV malignancy patients for their proper follow up and referral to higher speciality centres.

Serologic markers of Epstein-Barr virus reactivation are associated with increased disease activity, inflammation, and interferon pathway activation in patients with systemic lupus erythematosus

SLE is a clinically heterogeneous disease characterized by an unpredictable relapsing-remitting disease course. Although the etiology and mechanisms of SLE flares remain elusive, Epstein-Barr virus (EBV) reactivation is implicated in SLE pathogenesis. This study examined the relationships between serological measures of EBV reactivation, disease activity, and interferon (IFN)-associated immune pathways in SLE patients. Sera from adult SLE patients (n = 175) and matched unaffected controls (n = 47) were collected and tested for antibodies against EBV-viral capsid antigen (EBV-VCA; IgG and IgA), EBV-early antigen (EBV-EA; IgG), cytomegalovirus (CMV; IgG), and herpes simplex virus (HSV-1; IgG). Serological evidence of EBV reactivation was more common in SLE patients compared to controls as demonstrated by seropositivity to EBV-EA IgG (39% vs 13%; p = 0.0011) and EBV-VCA IgA (37% vs 17%; p = 0.018). EBV-VCA, CMV1, and HSV-1 IgG seropositivity rates did not differ between SLE patients and controls. Furthermore, concentrations of EBV-VCA (IgG and IgA) and EBV-EA (IgG) were higher in SLE patients. SLE patients with high disease activity had increased concentrations of EBV-VCA IgA (mean ISR 1.34 vs. 0.97; p = 0.041) and EBV-EA IgG levels (mean ISR 1.38 vs. 0.90; p = 0.007) compared with those with lower disease activity. EBV reactivation was associated with enhanced levels of the IFN-associated molecule IP-10 (p < 0.001) and the soluble mediators BLyS (p < 0.001) and IL-10 (p = 0.0011). In addition, EBV-EA IgG responses were enriched in two previously defined patient clusters with robust expression of IFN and inflammatory or lymphoid and monocyte responses. Patients in these clusters were also more likely to have major organ involvement, such as renal disease. This study supports a possible role for EBV reactivation in SLE disease activity.

Infection Related Immunoglobulin-M Antibodies Cross Reactive with Human Leucocyte Antigens

Objective: The first required feature for the patients, who will undergo allotransplantation, is HLA compatibility between donor and the recipient. In this study, it was aimed to indicate whether IgM antibodies that are produced during acute infection phase affect crossmatch tests or not, in addition to hitches that can occur in HLA incompatible transplants. Methods: Eighty-two patients with acute infection due to only one infectious agent and high serum IgM antibody levels were involved in this study. The patients had no alloimmunization (blood transfusion, pregnancy, and/or previous transplants). Fifty-five healthy individuals were used as HLA antigen source in order to evaluate Ab-Ag lymphocytotoxicity reactions. Results: The infectious agent distribution in the sera samples were as 25.6% Anti-Epstein-Barr virus capsid antigen (EBV VCA), 14.6% Anti-Cytomegalovirus (CMV), 17.1% Anti-Toxoplasma, 11% Anti-Hepatitis A Virus (HAV), 7.3% Anti-Rubella, 7.3% Anti-Varicella zoster virus (VZV), 4.9% Anti-Brucella, 3.7% Anti-Mumps, 2.97% Anti-Parvovirus B19, 1.9% Anti-Herpes simplex virus (HSV)-1, and 3.7% Anti-HBc. IgM antibody and HLA antigen reactions were analyzed by lymphocytotoxicity method in terasaki plates using peripheral blood lymphocytes of 55 healthy individuals. Conclusion: In lymphocytotoxicity test, the distribution of reactions that IgM antibodies gave to HLA antigens without class I-II differentiation according to infections were identified as 50% Brucella, 50% VZV, 44.4% HAV, 41.7% CMV, 42.9% EBV, 35.7% Toxoplasma, and 33.3% Rubella.

Применение ультразвукового исследования в диагностике хронического лимфопролиферативного синдрома ЛОР-органов у детей младшего возраста

The aim of study was to assess the diagnostic value of ultrasound diagnostics of chronic lymphoproliferative syndrome in the young children. 88 children aged 2–3 years with pathology of the lymphadenoid ring of the pharynx, accompanied by regional cervical lymphadenitis, needing surgery were examined. Endoscopy of the nasopharynx, otomicroscopy, impedance, ultrasound examination of cervical and submandibular lymph nodes, abdominal organs, complete blood count with a manual differential, ELISA to determine specific IgM, IgG to cytomegalovirus (CMV) antigens, to human herpes virus type 6 (HCV-6) antigens, to nuclear, viral capsid and early antigens complex Epstein – Barr virus (EBV), PCR in scrapes from the oropharyngeal mucosa and blood were performed. The patients were divided into two groups: group I with pronounced lymphadenopathy (lymph nodes conglomerates 31×13 mm in size or multiple) (n = 32), group II with moderate lymphadenopathy (single symmetrical painless lymph nodes less than 16 mm in size) (n = 56). In the group I, the following were statistically significant more frequent: snore and sleep apnea (Fisher's exact test, p &lt; 0,001, odds ratio (OR) 13,00, 95% confidence interval (CI) 4,439–38,07); manifestations of asthenic vegetative and intoxication syndromes (p &lt; 0,001, OR 7,80, CI 2,248–27,06); ultrasound signs of hepatic splenic syndrome (p &lt; 0,001, OR 34,71, CI 7,185–167,7); serological markers of contamination and active stages EBV infection (p &lt; 0,001, OR 16,71, CI 4,673–55,27); markers of mixt EBV + CMV + HHV-6 infections (p &lt; 0,001, OR 16,20, CI 3,327–78,87), compared to the group II. Regional cervical lymphadenitis with lymph nodes diameter more than 16 mm on ultrasound was a sign of pronounced chronic lymphoproliferative syndrome in the young children, in which half were found to have markers of the EBV infection active stage. The development of pronounced cervical lymphadenitis is associated with hepatic splenic syndrome, usually caused by the herpesvirus infections reactivation.

1091. Incidence of Post-Transplant Lymphoproliferative Disorders among Epstein-Barr Virus Donor Positive, Recipient Negative Adult Solid Organ Transplant Recipients

BackgroundEpstein-Barr virus (EBV) donor positive (D+), recipient negative (R-) serostatus is a major risk factor for post-transplant lymphoproliferative disorder (PTLD) in adult solid organ transplant recipients (SOTR). Few studies have systematically characterized absolute organ transplant type-specific incidence, timing, and outcomes of PTLD in adult EBV D+R- SOTR.MethodsWe retrospectively assessed the incidence, timing, and associated morbidity and mortality of biopsy-confirmed PTLD (WHO classification) among consecutive adult SOTR between Jan 1, 2000 and Apr 30, 2018 at a single university center, and who had a minimum 2 years of follow-up. Antibodies to EBV (viral capsid antigen and nuclear antigen) were assessed in candidates and donors by FDA-cleared ELISA assay. Donors with unknown serology were considered seropositive based on the known prevalence of >93% seropositivity in this donor population.ResultsAmong 4,923 SOTR, prior to transplant, 4,770 (96.9%) were R+ (regardless of donor status), 144 (2.9%) were D+R-, and 9 (0.2%) were D-R-. PTLD incidence by last follow-up was higher among D+R- (15/144 [10.4%]) than R+ (61/4,770 [1.2 %]), P < 0.0001, and occurred earlier after transplant (median 9.6 months [IQR 6.1-34.2] versus 35.1 months [IQR 7.1-73.1]), P= 0.003, respectively. Among D+R-, incidence was higher among recipients of non-kidney versus kidney organs (13/89 [14.6%] vs. 2/55 [3.6%], P = 0.05, respectively). Incidence in rank order was: pancreas (2/9 [22.2%]), lung (6/29 [20.7 %]), heart (2/21 [9.5%]), and liver (3/30 [6.7%]). PTLD histopathology was monomorphic in 9/15 [60%] and EBV-encoded RNA-1 (EBER-1) positive in 12/12 evaluable cases. Outcomes among the 15 PTLD cases included: graft failure without transplant in 3 (20%), graft failure with re-transplant in 2 (13.3%), and death within 6 months in 3 (20%).Table 1: Characteristics of the EBV Donor seropositive, Recipient seronegative (D+R-) cohort Figure 1: Cumulative Incidence of PTLD among the EBV D+R- cohort (all organs) Figure 2: Incidence of PTLD among the D+R- cohort, stratified by organ transplant type ConclusionAlthough rare overall, we identified a specific subgroup of adult SOT patients (EBV D+R- non-kidney recipients) whose absolute PTLD incidence and associated morbidity and mortality are high, and who should be targeted for future mechanistic or therapeutic studies.Disclosures All Authors: No reported disclosures

The positivity rate of Epstein-Barr virus anti-viral capsid antigen IgG among children with infectious mononucleosis in Diyala-Iraq

Background: Epstein-Barr virus (EBV) is a double-stranded linear DNA human herpesvirus that is transmitted primarily through saliva during childhood. Although the majority of primary EBV infections are clinically asymptomatic, clinical cases are presented as infectious mononucleosis (IMN) syndrome. Objectives: This study was conducted to explore the rate of EBV anti-VCA IgG among children who were clinically suspected as having IMN in Diyala province. Subjects and methods: This is a cross sectional study that was carried out during 2018 in Diyala province- Iraq. A total of 370 blood samples were collected from 190 children under 15 years of age who were clinically suspected as having IMN, and 180 apparently healthy children as controls. The anti EBV VCA IgG antibodies were detected in serum using the VCA IgG ELISA kit (from Dia.Pro Diagnostic Bioprobes srl - Italy). Statistical analysis was carried out using the SPSS- version 25. A statistical significance was considered whenever the P value was ≤ 0.05. Results: The results showed that the IgG positivity rate among suspected IMN patients was insignificantly higher in the age group 10-14 years old children (80.8%, P = 0.364). In control subjects the highest positivity rate was in the age group of 1-4 years with a statistically significant difference (79.5%, P = 0.002). In suspected IMN patients, the age group of 10-14 years had the highest mean concentration ± SD of anti-VCA IgG (44.018 ± 38.644 arbitrary units per milliliter (arbU/ml)), while in controls, the highest value (38.018 ± 34.908 arbU/ml) was in the age group of 1-4 years, with insignificant difference in either group (P = 0.257 and 0.072, respectively). The results also showed that in both suspected IMN patients and control subjects, females showed higher IgG positivity rate (70.6%, and 75.5%) compared to males (64.8%, and 65.1%) with insignificant difference in both groups (P = 0.392 and 0.126, respectively). Similarly, the IgG mean concentration ± SD was insignificantly higher in females in both suspected IMN patients and control subjects (P = 0.447 and 0.256, respectively). 21 (87.5%) IgM positive suspected IMN patients were also IgG positive with a statistically significant association (P = 0.028). Conclusion: The positivity rate of anti-EBV VCA IgG among apparently healthy subjects in Diyala province was 70.6%, and the rate increases with age, with slight association with clinical suspicion of infectious mononucleosis.

Self-collected oral flocked swabs to measure prevalence of Epstein-Barr Virus antibodies and DNA amongst university students

Epstein-Barr Virus (EBV) exposure and illness is common in undergraduate university students and may affect academic achievement, social life, and quality of life. We designed a study to measure EBV exposure (EBV-IgG, either Epstein-Barr nuclear antigen 1 (EBNA-1)-IgG or viral capsid antigen (VCA)-IgG) and current viral shedding (EBV-DNA) using self-collected oral swabs among university undergraduate students. Of 184 students enrolled, 129 (70.1%) tested positive for EBV-IgG. Salivopositivity was associated with being in a current relationship, but not with enrollment year. Forty (21.7%) of the participants tested positive for EBV-DNA, which was associated with all symptom scores, including history of sore throat, fever, swollen glands, muscle weakness, and fatigue in the previous 6 months. Our findings suggest that noninvasive, self-collected oral flocked swabs are feasible and potentially valuable for measuring EBV IgG antibodies and DNA.

Primary Epstein-Barr Virus Infection in Healthy Children in Saudi Arabia: A Single Hospital-Based Study.

Primary Epstein-Barr virus (EBV) infection presents typically with features of infectious mononucleosis (IM) but it may present with atypical symptoms. We aim to evaluate the epidemiological, clinical and laboratory characteristics of primary EBV infection in children in western Saudi Arabia. A retrospective analysis of the electronic data of all children who were admitted to the hospital and were tested for EBV-viral capsid antigen (VCA) IgM in the period from 1 January 2018 to 31 December 2019. All data of the children with positive EBV-VCA IgM were collected. Patients were divided into two groups; IM and the non-typical presentations groups. Fort-two patients had positive EBV-VCA IgM; 71% had IM and 29% had non-typical presentations. IM was more common in early childhood (46.7%). The non-typical presentations were more in infants below 1 year (50%). Adolescents were less affected (6.7% and 16.7%, respectively). Time to diagnose EBV in the non-typical presentations group was longer than IM group; [3.4 (3.2-4.6) vs. 4.7 (4.1-5.5), p = 0.039]. The total leucocytes count was higher in the IM syndrome group compared to the non-typical presentation group [11 (10.3-17.7) vs. 5.5 (4.5-6.4), p < 0.0001]. Primary EBV infection in healthy children in Saudi Arabia occurs more frequently in the younger age groups. IM syndrome occurs more frequently in early childhood. The non-typical presentation occurs more frequently in infants. While adolescents are less commonly affected by primary EBV.

Lack of serologic association of human herpesvirus-8 (KSHV) in patients with monoclonal gammopathy of undetermined significance with and without progression to multiple myeloma

AbstractBecause human herpesvirus-8 (HHV-8) DNA has been found in multiple myeloma (MM) patients by polymerase chain reaction, it was suggested that HHV-8 may play a role in the transformation of monoclonal gammopathy of undetermined significance (MGUS) to MM. Therefore, 362 MGUS sera with and without progression to MM were tested for IgG antibody to HHV-8. Only 7.8% of the MGUS sera contained HHV-8 antibody to lytic proteins, and IgG antibody to HHV-8 latent antigen was even lower than lytic antibody (2.9%). No differences were observed in the distribution of antibody to HHV-8 in sera from MGUS patients who progressed to MM. The seroprevalences of HHV-8 in MGUS (7.8%), MM (5.4%), and healthy donors (5.9%) were similar, thus arguing for the lack of epidemiologic evidence of HHV-8 participation in the pathogenesis of MM. MGUS patients were immune competent in response to Epstein-Barr virus (EBV) infection because 97% contained antibody to EBV virus capsid antigen.

Monozygous twins with Epstein-Barr infection in the nasopharynx

The article describes a clinical case of monozygotic twins with hypertrophy of the organs of the lymphopharyngeal ring. The examination revealed IgG to the Epstein-Barr virus capsid antigen in both patients. One twin had Epstein-Barr virus DNA in the sample from the oropharynx. It was this child who had complaints typical of patients with adenoid vegetation, and he required surgical treatment (endoscopic shaver adenotomy and radio wave bilateral tonsillotomy). At the time of the initial examination and in the absence of complaints the second twin revealed no DNA of Epstein-Barr virus in the oropharynx. This patient was diagnosed with adenoids of 1-2 degree. Due to the complaints of the second twin that appeared during the following year of observation, with previously negative results on active Epstein-Barr virus markers served as the reason for a repeated specific laboratory examination. Epstein-Barr virus DNA was found in a sample from this child’s oropharynx. This case using the twin control method by partner enabled us to demonstrate the significance of Epstein-Barr virus in the pathogenesis and clinic manifestations of chronic diseases of the lympho-pharyngeal ring organs in children.

A combination of two ELISA tests for nasopharyngeal carcinoma screening in endemic areas based on a case-control study.

For populations with a high risk of nasopharyngeal carcinoma (NPC) in Guangdong province in southern China, mass screening is the first choice to prevent death from NPC. To improve the performance of NPC screening, we used a combination based on the IgA antibody against the Epstein-Barr virus (EBV) capsid antigen (VCA-IgA) and the IgA antibody against Epstein-Barr virus nuclear antigen 1 (EBNA1-IgA) to NPC screening by enzyme-linked immunosorbent assay (ELISA). A multiplication model was applied to measure the level of the combination. We evaluated the NPC screening effect of the markers.A case-control study was performed to assess the NPC screening effect of the markers. A total of 10,894 serum specimens were collected, including 554 samples from NPC patients and 10,340 samples from healthy controls. In the training stage, 640 subjects were randomly selected, including 320 NPC cases and 320 healthy controls. In the verification stage, 10,254 subjects were used to verify the NPC screening effect of the combination. Receiver operating characteristic (ROC) analysis was performed. In the verification stage, the combination achieved an sensitivity of 91.45%, a specificity of 93.45%, and an area under the ROC curve (AUC) of 0.978 (95% CI [0.968–0.987]). Compared with VCA-IgA and EBNA1-IgA individually, the combination had an improved screening performance. A probability (PROB) calculated by logistic regression model based on VCA-IgA and EBNA1-IgA was applied to NPC screening by ELISA in China. The AUC of the combination was a little bit larger than the PROB. There was a slight increase (3.13%) in the sensitivity of the combination compared to the sensitivity of the PROB, while the specificity was lower for the combination (92.50%) than for the PROB (95.94%). We successfully applied a combination of two ELISA tests based on VCA-IgA and EBNA1-IgA for NPC screening by using a multiplication model. The results suggested that the combination was effective and can be an option for NPC screening.

Serological Evidence for the Association Between Epstein-Barr Virus Infection and Sjögren's Syndrome.

BackgroundExposure to Epstein-Barr virus (EBV) infection has been hypothesized to be an important risk factor for multiple rheumatic diseases, but the serological evidence so far for its role in Sjögren’s syndrome (SjS) is not clearly established yet. This study aimed to assess the seroepidemiological associations of antibodies to EBV with SjS.MethodsA seroepidemiological study containing 119 patients with SjS and 65 healthy controls was first performed, in which the associations of SjS with four commonly studied EBV antibodies including IgM-anti-viral capsid antigen (anti-VCA) antibody, IgG-anti-VCA antibody, IgG-anti-early antigen (anti-EA) antibody, and IgG-anti-EBV nuclear antigen 1 (anti-EBNA1) antibody were evaluated. A systematic review and meta-analysis of eligible seroepidemiological studies was also carried out, and data syntheses were performed using random-effect meta-analysis.ResultsIn the case-control study, the patients with SjS had both a significantly higher prevalence of IgG-anti-EA antibody positivity (31.9% vs. 3.1%, P < 0.001) and high titers of IgG-anti-EA antibody (P < 0.001) than healthy controls. The titer of IgG-anti-VCA antibody was significantly increased in the patients with SjS compared with healthy controls (P < 0.001). IgG-anti-EA antibody seropositive patients with SjS had lower levels of both C3 (P = 0.002) and C4 (P = 0.02), and the titer of IgG-anti-EA antibody was inversely related to the levels of both C3 (r = -0.31, P < 0.001) and C4 (r = -0.20, P = 0.03). A total of 14 eligible studies on the serological associations between EBV infection and SjS were finally included into the meta-analysis, which suggested obvious associations of SjS with IgM-anti-VCA antibody [Odds ratio (OR) = 5.77, 95%CI 1.73–19.25, P = 0.004] and IgG-anti-EA antibody (OR = 9.97, 95%CI 4.58-21.67, P < 0.00001).ConclusionsThe findings from this study provide strong serological evidence for the association between EBV infection and SjS. SjS has obvious associations with IgM-anti-VCA antibody and IgG-anti-EA antibody. IgG-anti-EA antibody is linked to low levels of C3 and C4 in the patients with SjS, the significance of which needs to be addressed in further studies.

Prevalence of seropositivity of selected herpesviruses in patients with multiple sclerosis in the North of Jordan

BackgroundMultiple sclerosis (MS) is a neurological disease that is caused by an autoimmune response that results in the neuron’s demyelination in the central nervous system. The exact etiology of MS is not clear; however, several environmental and genetic factors are believed to participate in its initiation and development, including exposure to viruses. This study aims to investigate the association between the seropositivity and antibody titer of selected herpesviruses and MS in Jordanian MS patients.MethodIn this study, 55 MS patients and 40 age- and gender-matching apparently healthy volunteers were recruited from two main hospitals in the north of Jordan. MS patients were grouped into three types of MS based on the clinical presentation of the disease. Blood samples were collected from the participants and the IgG antibodies for human herpesvirus 6 (HHV-6), Epstein-Barr virus (EBV) nuclear antigen (EBNA), EBV viral capsid antigen (VCA) and varicella-zoster virus (VZV) were assayed by ELISA. The prevalence of seropositivity and the antibody level for each of the antibodies were compared between MS patients and controls and between the three types of MS.ResultsThere was no significant difference in the prevalence of seropositivity and in the levels of antibodies for HHV-6, EBNA and VCA between MS patients and controls and between the three types of MS. In contrast, the number of seropositive patients and the level of IgG antibodies for VZV were significantly higher in MS patients compared to the control.ConclusionThis study showed that patients with MS in the north of Jordan were more likely to be seropositive for VZV than the general population. Based on this finding, we recommend further studies to evaluate the seropositivity to VZV to be carried out in other parts of Jordan and the greater middle east to find out if there is a correlation between MS and previous infection with VZV.

Diagnostic value of serological and molecular biological tests for infectious mononucleosis by EBV in different age stages and course of the disease.

Epstein-Barr virus (EBV)-based serologic antibody and viral nucleic acid assays have been found to be feasible means to diagnose infectious mononucleosis (IM) caused by EBV in children. In this study, we will further explore theirdiagnostic value for IM by EBV in different age stages and over the course of the disease. A collection of 616 children from clinically suspected IM cases was studied. Indirect immunofluorescence (IIF) for EBV-specific antibody (Euroimmun) combined with plasma EB viral nucleic acid assay (real-time fluorescence quantitative polymerase chain reaction reverse-transcription polymerase chain reaction) were used as reference methods. The diagnostic efficiency of the peripheral blood routine test, serologic antibody test, and plasma EB viral nucleic acid assay for the diagnosis of IM was evaluated, respectively. The sensitivity, specificity, Youden' index and the area under curve (AUC) were 93.08%, 87.77%, 0.81 and 0.904 (95% confidence interval [CI]: 0.878-0.931) for the peripheral lymphocyte test (lymphocytosis > 5 × 109 /L), 98.27%, 91.13%, 0.89 and 0.947 (95% CI: 0.927-0.967) for the plasma EBV-DNA test, and 84.08%, 96.33%, 0.80 and 0.902 (95% CI: 0.874-0.930) for the EBV viral capsid antigen (VCA)-IgG avidity test. The plasma EBV-DNA test has ahigher diagnostic value than the VCA-IgG avidity test in children aged <6 years, especially aged <3 years; the peripheral lymphocyte test and plasma EBV-DNA test are suitable for the early stage of the disease, while the VCA-IgG avidity test for after 7 days of the disease. EBV antibody detection (IIF) should be combined with EBV nucleic acid detection in children age <6 years and the early stage of the disease.

Status of humoral and cellular immune markers in human T-cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers in northeastern Iran, Mashhad.

It is estimated that about 10-20 million peoples are infected with human T-cell leukemia virus type 1 (HTLV-1) around the world and suffered from HTLV-related diseases. The present study was aimed to evaluate the cellular immunity, T-cell activation, humoral immunity, and inflammatory response hallmarks which affect HTLV-1-associated disease progression. A total of 78 participants were included in the study, comprising 39 HTLV-1 asymptomatic careers (ACs) and 39 healthy controls. The HTLV-proviral load (PVL) was determined via real-time PCR technique, and anti-HTLV antibody, sIL2R, sCD30, Neoptrin, hs-CRP, IgE, anti-VCA, anti-EBNA, and anti-EA were assessed by ELISA method. Mean PVL in ACs was 352.7 ± 418.7 copies/104 PBMCs. A significant higher level of sIL-2R was observed in ACs (P < 0.0001). Anti-VCA antibody titer in ACs and healthy controls was 80.72 ± 105.95 and 156.05 ± 130.71, respectively (P = 0.007). Intriguingly, suppression in ACs immune response was not observed. Resultantly, HTLV-1 infection has no effect on the humoral immune response in ACs but greater T-cell activation and function cellular responses were detected. Finally, more studies on various immune markers in adult T-cell leukemia/lymphoma (ATLL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients are greatly needed to illuminate the association of ACs' immune status with the development of the related diseases.

S2555 Longstanding Hepatosplenomegaly in an Undiagnosed Sarcoidosis Patient

INTRODUCTION: Sarcoidosis, a multisystem granulomatous disease, typically affects the lungs and lymph nodes. Although there is hepatic involvement in approximately 66% of cases, the liver is rarely the cause of symptoms.We present a case of longstanding sarcoidosis in a young patient whose delayed diagnosis likely resulted in worsened portal hypertension and severe pancytopenia. CASE DESCRIPTION/METHODS: In 2015, a 25 year-old Panamanian woman was referred to Hepatology for elevated liver tests. Initial workup ruled out autoimmune hepatitis and viral hepatitis. She was lost to follow-up until 2017 when she saw a different hepatologist for elevated liver tests. As noted in Table 1, she developed significant cholestasis during that interval. Serologic studies for primary cholestatic liver disease were negative. Imaging showed hepatosplenomegaly but she was again lost to follow-up. In 2019, she presented to the Emergency Department with severe abdominal pain. Labs showed pancytopenia and computed tomography (CT) of the abdomen/pelvis showed hepatosplenomegaly. She was referred to Hematology/Oncology. Bone marrow biopsy was negative. She was again referred to Hepatology. She reported a chronic rash on her lower extremities, but was otherwise asymptomatic. Skin biopsy suggested erythema nodosum. Physical exam was notable for massive splenomegaly, confirmed by CT (Figure 1). Labs revealed pancytopenia and persistent cholestasis. An extensive workup for granulomatous diseases and systemic fungal, viral and mycobacterial infections was completed. Angiotensin converting enzyme (ACE) was markedly elevated (Table 1). Ultimately, liver biopsy was performed. Results confirmed granulomatous hepatitis. (Figure 2). After referral to the Sarcoidosis team, she was noted to have significantly elevated interleukin-2 (IL-2) level, consistent with the diagnosis. DISCUSSION: This case nicely illustrates the natural history of hepatic sarcoidosis. Our patient presented with a normal hematologic profile and mildly elevated liver tests, however she progressed to develop significant cholestasis, portal hypertension and pancytopenia. Earlier recognition and treatment may have hindered progression of portal hypertension. Sarcoidosis should be strongly considered in the diagnostic workup of elevated liver tests, especially in young patients who are at highest risk . In addition to ACE, absolute lymphocyte count and IL-2 level are highly sensitive for sarcoidosis and were also abnormal in our patient.Table 1.: Lab values from 2015-2020. Abbreviations: VCA: Viral Capsid Antigen; EBNA: Epstein-Barr Nuclear AntiigenFigure 1.: CT abdomen and Pelvis showing hepatosplenomegaly.Figure 2.: Liver biopsy pathology showing granulomatous hepatitis.

S1438 Epstein-Barr Virus Infection Masquerading as Cholestasis in a Patient With Gallstone Disease

INTRODUCTION: Epstein-Barr virus (EBV) induced infectious mononucleosis (IMN) is primarily a disease of adolescents and young adults. Hepatobiliary manifestations like acalculous cholecystitis, cholestasis and acute hepatitis are uncommon, and EBV infection will be of low suspicion when there is concomitant cholecystolithiasis. We report a case of EBV infection in an adult who presented with possible gallstone disease and cholestasis. CASE DESCRIPTION/METHODS: A 57-year-old woman with past medical history of migraine presented with fever, diffuse abdominal pain, nausea and vomiting of 6 days duration. She denied any sore throat. On examination she had scleral icterus, bilateral tender cervical and axillary lymphadenopathy and diffuse abdominal tenderness on palpation. Lab abnormalities noted were total bilirubin 4.7 mg/dl, direct bilirubin 2.6 mg/dl, AST 173 U/L, ALT 355 U/L, ALP 535 IU/L, GGT 349 U/L. Computed tomography (CT) of abdomen showed cholelithiasis with features of acute cholecystitis. She underwent Endoscopic ultrasound (EUS) and Endoscopic retrograde cholangiopancreatography (ERCP) with biliary sphincterotomy, balloon sweep with removal of sludge, and placement of a biliary stent, due to clinical suspicion of ascending cholangitis. Esophagogastroduodenoscopy showed erosive gastritis (Figure 1) and was biopsied. Liver chemistry remained unchanged despite this. Meanwhile peripheral smear showed polymorphous lymphocytes including a few atypical forms (Figure 2). Monospot test was positive, while HIV and acute hepatitis panel were negative. EBV early D Antibody and IgM antibodies to Viral capsid antigen were positive. The gastric biopsy demonstrated expansion of the lamina propria by atypical lymphoid infiltrates, and positive immunohistochemical studies for EBV (Figure 3). She was treated with antibiotics for her cholecystitis. She had significant clinical improvement at the time of her discharge at 7 days and laboratory improvement on follow up. An elective cholecystectomy has been arranged as an outpatient procedure. DISCUSSION: EBV can have gastrointestinal and hepatobiliary manifestations, but rarely the primary presentation. Superimposed cholecystolithiasis can sometimes necessitate invasive evaluation. EBV should be in the differential diagnosis in patients with generalized lymphadenopathy who have cholestasis, hepatitis or mixed pattern of liver injury, especially when the liver chemistry remains unchanged despite biliary decompression.Figure 1.: EGD showing erosive gastritis.Figure 2.: Peripheral smear demonstrated atypical lymphocytes.Figure 3.: Gastric biopsy showed lymphoid infiltrates in lamina propria and had positive immunohistochemical studies for EBV.

S2614 Cholestatic Hepatitis From Acute Epstein-Barr Virus Infection

INTRODUCTION: Primary Epstein-Barr Virus infection (EBV) presents as a triad of fever, posterior lymphadenopathy and pharyngitis. Hepatocellular involvement is limited to transient, mild, asymptomatic elevations of aminotransferases. Clinical manifestations of hepatitis are rarely the presenting feature of the disease and severe cholestasis is exceedingly rare. We present a patient with atypical presenting features found to have cholestatic hepatitis due to acute EBV infection. CASE DESCRIPTION/METHODS: A 38-year-old male with no medical history presented with right upper quadrant (RUQ) abdominal pain for 1 week associated with malaise, dyspnea, nausea, emesis, and fever to 38.8 degrees Celsius. His social history consisted of safe sex practices, no sick contacts, and no drug or alcohol use. On examination, he was afebrile and hemodynamically stable. There was no jaundice, scleral icterus or lymphadenopathy. There was mild tonsillar erythema without edema or exudate. He had RUQ and epigastric tenderness to palpation without notable hepatosplenomegaly. His labs showed no leukocytosis with elevated aspartate aminotransferase (AST) 234 IU/L, alanine aminotransferase (ALT) 383 IU/L, alkaline phosphatase 432 IU/L, and total and direct bilirubin of 3.4 and 1.6 mg/dL, respectively. ALT and AST peaked at 743 and 582 IU/L, respectively. HIV and hepatitis panel were negative. RUQ ultrasound showed normal gallbladder (GB) wall thickness of 2.7 mm with mild distention, trace pericholecystic fluid, and no biliary dilation. Magnetic resonance cholangiopancreatography showed mild hepatosplenomegaly, a normal GB and no biliary obstruction. Further workup revealed a positive Monospot with >160 units/ml of EBV antibodies to viral capsid antigen IgM and indeterminate EBV antibody to viral capsid antigen IgG, indicating acute EBV infection. DISCUSSION: EBV cholestasis is thought to be secondary to inflammation of the bile duct and direct damage to hepatic cells by autoantibody-mediated activation of free radicals. A literature review revealed that EBV has been reported to cause a hepatocellular pattern of elevated aminotransferases however cholestatic patterns are infrequently reported and thus may cause a diagnostic dilemma. The existing literature reports this phenomenon in pediatrics, adolescents, or patients in the second decade of life. Our case highlights the importance of including EBV infection in the differential diagnosis of cholestatic hepatitis at any age, particularly when no demonstrable cholecystitis is present.Table 1.: Liver and biliary marker trend throughout hospitalizationFigure 1.: Abdominal MRI demonstrating hepatomegaly and splenomegaly, measuring 15.1 cm anterior-posteriorly, and 13.9 cm craniocaudally.Figure 2.: Abdominal MRI demonstrating hepatosplenomegaly.