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The molecular characterization of fatal infectious mononucleosis
Myra J Wick1, Kristine P Woronzoff-Dashkoff, Ronald C McGlennen
1Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis 55455, USA.
Abstract:
We describe a retrospective study of 4 cases of sporadic fatal infectious mononucleosis (IM), 1 case of fatal IM, and 1 case of sporadic severe IM. Patients were 26 months to 17 years old; 3 were male. Five died of complications of IM. All 5 of these patients had the Epstein-Barr virus (EBV) present in examined tissue specimens; EBV was monoclonal in 3 patients and biclonal in 1. EBV clonality studies were not performed in the remaining patient. All 5 patients also had monoclonal gene rearrangements. The sixth patient survived despite a life-threatening clinical course; EBV was oligoclonal, and gene rearrangements were not detected. EBV clonality and gene rearrangement studies may be usefulfor predicting which patients with clinically aggressive IM are at highest risk for fatal outcome. Patients in whom IM has a fatal outcome are more likely to have monoclonal or biclonal EBV and immunoglobulin heavy chain or T-cell receptor gene rearrangements. In contrast, patients with nonfatal IM may lack monoclonal EBV and monoclonal rearrangements of the aforementioned genes. The reasons EBV induces a monoclonal proliferation only in some patients remain to be elucidated.
Insights
Fatal infectious mononucleosis (IM) cases often show monoclonal Epstein-Barr virus (EBV) and gene rearrangements. These markers may help predict fatal outcomes in aggressive IM, aiding early intervention for high-risk patients.
Area of Science:
- Virology
- Immunology
- Pathology
Background:
- Infectious mononucleosis (IM), a common viral illness, can rarely lead to severe or fatal outcomes.
- The Epstein-Barr virus (EBV) is the primary causative agent of IM.
- Understanding the viral and host genetic factors associated with severe IM is crucial for risk stratification.
Observation:
- A retrospective study analyzed 6 cases of severe or fatal infectious mononucleosis in patients aged 26 months to 17 years.
- Five of the six patients died from IM complications.
- Epstein-Barr virus (EBV) was detected in tissue specimens of all fatal cases.
Findings:
- Monoclonal or biclonal Epstein-Barr virus (EBV) and monoclonal gene rearrangements (immunoglobulin heavy chain or T-cell receptor) were observed in 5 of the 5 fatal IM cases.
- The single surviving patient with a severe clinical course had oligoclonal EBV and no detected gene rearrangements.
- EBV clonality and gene rearrangement status appear to correlate with fatal outcomes in clinically aggressive IM.
Implications:
- EBV clonality and gene rearrangement studies may serve as valuable biomarkers for predicting fatal outcomes in patients with aggressive infectious mononucleosis.
- Identifying patients at highest risk for fatal IM can guide clinical management and therapeutic strategies.
- Further research is needed to elucidate the mechanisms by which EBV induces monoclonal proliferation in a subset of patients.