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Epstein-Barr virus infection rapidly progressing to monoclonal lymphoproliferative disease in a child with selective
V Schuster1, H W Kreth, H K Müller-Hermelink
1Department of Paediatrics, University of Würzburg, Federal Republic of Germany.
Insights
A rare Epstein-Barr virus (EBV) infection led to fatal lymphoproliferation in a child due to a selective immunodeficiency. This case highlights the critical role of T-cell function in controlling EBV-driven B-cell cancers.
Area of Science:
- Immunology
- Virology
- Pediatric Oncology
Background:
- Epstein-Barr virus (EBV) is a common human herpesvirus associated with various lymphoproliferative disorders.
- Chronic active EBV infection (CAEBV) is a rare, severe condition characterized by persistent EBV replication and immune system dysregulation.
- Understanding the immunopathogenesis of EBV-associated lymphoproliferation is crucial for developing effective therapies.
Observation:
- A previously healthy 30-month-old boy presented with fever, hepatosplenomegaly, and lymphadenopathy, rapidly progressing despite treatment.
- EBV DNA was detected in bone marrow and lymph node biopsies, with evidence of chronic active EBV infection.
- Lymph node cells exhibited monoclonal immunoglobulin heavy chain gene rearrangements, indicating B-cell clonal expansion.
Findings:
- The patient displayed a selective immunodeficiency characterized by impaired T-cell cytotoxic function against EBV-infected B-cells and K562 target cells.
- Peripheral blood mononuclear cells failed to control the outgrowth of autologous EBV-infected B-cells.
- Despite increased CD8+ T-cells, functional assays revealed a profound defect in cell-mediated immunity.
Implications:
- This case underscores a critical link between T-cell dysfunction and the rapid development of EBV-associated monoclonal lymphoproliferation.
- The findings suggest that targeted immunotherapies aimed at restoring T-cell cytotoxicity may be beneficial in managing severe EBV-related disorders.
- Further research into the genetic and molecular basis of such selective immunodeficiencies is warranted to improve diagnostic and therapeutic strategies.
Abstract:
We report on a 30-month-old previously healthy Turkish boy who presented with fever, hepatosplenomegaly and generalized lymphadenopathy. He died 4 months after admission in spite of treatment with steroids, acycloguanosine and cyclophosphamide. Epstein-Barr virus (EBV) DNA was detected in the patient's bone marrow and in a lymph node biopsy. Cells from the lymph node biopsy showed monoclonal rearrangements of immunoglobulin heavy chain genes but no rearrangements of T-cell receptor beta-chain genes or immunoglobulin kappa chain genes. Serological data indicated chronic active EBV infection. There was a slight increase of CD8 positive cells in peripheral blood and a normal response to T-cell mitogens. However, T-cell lines established with interleukin 2 from lymph node biopsy completely failed to kill autologous EBV-transformed B-cells and K 562 target cells. Moreover, in regression tests the patient's peripheral blood mononuclear cells completely failed to limit outgrowth of autologous EBV infected B-cells. We conclude that the patient's selective immuno-deficiency had led to the rapid development of EBV-associated monoclonal lymphoproliferation.