Primary Infectious Mononucleosis Research Articles

Comparison of immune responses in children with infectious mononucleosis caused by Epstein-Barr virus at different infection stages.

Infectious mononucleosis (IM) is a common infectious disease in children mainly caused by Epstein-Barr virus (EBV) infection, followed by abnormal immune response, and resulting in serious complications. However, there are few clinical analyses of immune responses in children with IM at different stages. This study combined EBV serological test and EBV DNA test to diagnose the infection status of children with IM, and the infection status was divided into primary acute IM infection (AIM), primary late IM infection (LIM) and reactivation IM infection (RIM). The results revealed that the absolute numbers of leukocytes and CD8+ T lymphocytes in primary IM infection were significantly higher than those in reactivation infection, while the frequencies of CD4+ T lymphocytes and B cells were significantly lower than those in reactivation infection. In addition, the activities of ALT, AST, α-HBDH and LDH in liver function indicators in primary infection were significantly increased compared with reactivation infection. Similarly, the EBV DNA levels of the primary infection were significantly higher than that of the reactivation infection. There are differences in immune response at different stages of infection, which can provide guidance for effective treatment in children with IM infection.

Memory B cells producing somatically mutated antiphospholipid antibodies are present in healthy individuals

AbstractAntiphospholipid antibodies (aPLs) are associated with thrombosis and recurrent abortions during autoimmune pathologies, but they are also produced in healthy individuals and during infectious diseases. To analyze the possible links between physiologic and pathologic aPLs, it is of importance to characterize normal aPL production. We took advantage of the known tropism of Epstein-Barr virus (EBV) for B cells in general, and memory B cells in particular, during primary infectious mononucleosis (IMN) in 3 patients to get access to anticardiolipin (aCL)-producing B cells. Flow cytometry analysis of these cells showed that, depending on the patient, 10% to 60% of immunoglobulin M (IgM) aCL-producing B cells express the CD27 marker of memory B cells. Single cell sorting of aCL B cells, followed by single cell reverse transcription-polymerase chain reaction (RT-PCR) amplification of their immunoglobulin variable region genes, showed that some of these cells produce mutated forms of aCL antibodies, confirming their memory B-cell origin. Considering that, during primary IMN, EBV infects and expands already pre-existing memory B cells, we conclude that healthy individuals have a discrete pool of aCL memory cells able to produce mutated forms of antibodies. The implications of this new information are discussed in light of different hypotheses regarding the origin of aCL. (Blood. 2003;102:2459-2465)

Epstein-Barr Virus Induces Expression of the LPAM-1 Integrin in B Cells In Vitro and In Vivo.

Epstein-Barr virus (EBV) infects the oropharynx but, surprisingly, frequently induces B cell proliferation in the gut of immunosuppressed individuals. We found that EBV infection in vitro induces the expression of the LPAM-1 integrin on tonsillar B cells and increases it on peripheral blood cells. Similarly, LPAM-1 was induced in the tonsils of patients undergoing primary infectious mononucleosis. EBV-induced LPAM-1 bound to the MAdCAM-1 addressin, which allows B cell homing to the gastrointestinal mucosa-associated lymphoid tissue (GALT). Thus, we hypothesized that EBV-induced LPAM-1 could induce relocation of infected B cells from the tonsil to the GALT. In situ hybridization with an EBER-specific probe revealed the frequent presence of EBV-infected cells in the pericolic lymph nodes of healthy individuals. Relocation of infected B cells into the GALT would expand the EBV reservoir, possibly protecting it from T cells primed in the oropharynx, and explain why EBV induces lymphoid tumors in the gut.IMPORTANCE EBV causes tumors in multiple organs, particularly in the oro- and nasopharyngeal area but also in the digestive system. This virus enters the body in the oropharynx and establishes a chronic infection in this area. The observation that the virus causes tumors in the digestive system implies that the infected cells can move to this organ. We found that EBV infection induces the expression of integrin beta 7 (ITGB7), an integrin that associates with integrin alpha 4 to form the LPAM-1 dimer. LPAM-1 is key for homing of B cells to the gastrointestinal tract, suggesting that induction of this molecule is the mechanism through which EBV-infected cells enter this organ. In favor of this hypothesis, we could also detect EBV-infected cells in the lymph nodes adjacent to the colon and in the appendix.

The early diagnostic value of EBV-DNA load in plasma and PBMC for children's primary infectious mononucleosis

Objective To investigate the early diagnostic value of EBV-DNA load in Plasma and peripheral blood mononuclear cells (PBMCs) for Children's Primary Infectious Mononucleosis(IM). Methods The plasma and PBMCs samples were collected from children of 67 cases with primary IM (IM groups) and 75 healthy cases (H groups) during April, 2015 to March, 2016 in our hospital. The EBV-DNA load in PBMCs and plasma samples were quantified by Real-time PCR. Statistical differences between two groups were analyzed by using Mann-Whitney Test. Receiver operating characteristic curves (ROC) were analyzed to assess the early diagnostic value of EBV-DNA load for primary IM. Results Levels of EBV-DNA in the samples of plasma were significantly higher in the IM groups (median, 380 IU/ml) compared to the H groups (Z=-9.332, P<0.01), and levels of EBV-DNA in the PBMCs samples were also significantly higher (median, 2.51×105 IU/ml, Z=-9.194, P<0.01). According to ROC curve analysis, the AUC of EBV-DNA load in plasma was 0.908, the most appropriate cut-off value was 12.5 IU/ml (sensitivity: 83.6% and specificity: 94.7%), the AUC of EBV-DNA load in PBMCs was 0.944, the most appropriate cut-off value was 2.19×104 IU/ml (sensitivity: 89.6% and specificity: 82.7%), the AUC of combined testing(plasma and PBMCs) was 0.967(sensitivity: 98.3% and specificity: 99.0%). Conclusions Combined testing of plasma and PBMCs have better clinical value, it may be useful for the diagnosis of early stage of Children's Primary Infectious Mononucleosis.(Chin J Lab Med, 2017, 40: 443-446) Key words: Infectious Mononucleosis; Herpesvirus 4, human; DNA, viral; Viral load; Early diagnosis

Primary Epstein-Barr virus infection in a 40-day-old infant

Most cases of primary Epstein-Barr virus (EBV) infection during infancy and early childhood are mild or subclinical; therefore, the diagnosis of an EBV infection is not performed easily in this age group. Infectious mononucleosis (IM) is rarely reported during infancy. We report a 40-day-old infant with cervical node enlargement, cough, and coryza symptoms who was finally identified as having a case of primary IM based on the patient's clinical features and serological tests. © 2013 - IOS Press and the authors. All rights reserved.

What delay should there be between primary infectious mononucleosis and renal transplantation?

A 17-yr-old girl in end-stage renal failure was due to undergo living-related pre-emptive renal transplantation when she developed acute infectious mononucleosis (AIM) from Epstein-Barr virus (EBV). In view of the risk of post-transplant lymphoproliferative disorder (PTLD) we were unsure as to the optimal delay between AIM and renal transplantation. This report describes the process used to determine maturation of the immune response to EBV using a combination of serology, immunophenotyping and molecular viral load estimation. These tests showed that EBV had not been cleared and dialysis was instituted rather than proceed directly to transplantation. After EBV viral load became undetectable in the blood, living-related donor was successfully performed 13 months after AIM. With 42-month post-transplant follow up there has been no evidence of PTLD.

Epstein-Barr virus DNA in peripheral blood leukocytes of patients with posttransplant lymphoproliferative disease.

We tested the hypotheses that Epstein-Barr virus (EBV) DNA levels in peripheral blood leukocytes (PBL) of transplant recipients with posttransplant lymphoproliferative disease (PTLD) (1) exceed those of patients without PTLD, (2) rise with or before clinical detection of the disease, and (3) fall with effective therapy. Using the polymerase chain reaction (PCR) and an endpoint dilution technique, we compared EBV DNA levels in sequential specimens from 5 patients with PTLD, 16 solid organ transplant recipients without PTLD, and 5 young adults with primary infectious mononucleosis (IM), and in single specimens from 21 healthy seropositive subjects. EBV DNA levels in the first two groups rose with induction of immunosuppression despite prophylactic acyclovir. Markedly elevated levels of EBV DNA were seen in 4 of 5 patients with PTLD at or before clinical diagnosis. The peak levels in these patients exceeded those of transplant recipients without PTLD (P = 0.02) and healthy adults with IM (P = 0.02). EBV DNA levels fell dramatically with effective therapy. Four of 21 healthy seropositive subjects demonstrated low levels of EBV DNA, similar to levels seen late in the course of patients with IM. We conclude that a semiquantitative PCR assay for EBV DNA in PBL can assist in the detection of PTLD and in monitoring the effect of therapy.