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Target cells of Epstein-Barr-virus (EBV)-positive post-transplant lymphoproliferative disease: similarities to EBV-positive Hodgkin's lymphoma.
- Source :
-
Lancet (London, England) [Lancet] 2003 Jan 18; Vol. 361 (9353), pp. 217-23. - Publication Year :
- 2003
-
Abstract
- Background: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD) encompasses a histologically broad range of lesions, arising from the expanded pool of EBV-infected B cells in the immunocompromised host. Identification of the precise cellular origin of these tumours could clarify their pathogenesis.<br />Methods: Of 13 cases of EBV-positive cases of PTLD characterised by histological analysis, pattern of EBV gene expression, and clinical course, 11 had monoclonal or biclonal lesions in which we determined the progenitor B cell by immunoglobulin heavy chain (IgH) genotyping.<br />Results: Two tumours had a naive B cell genotype and two showed patterns of IgH somatic mutation typical of antigen-selected (post-germinal-centre) memory cells. All four arose early post-transplant and expressed the markers of EBV transformation--Epstein-Barr nuclear antigen (EBNA) 2 and latent membrane protein (LMP) 1. However, seven tumours, either of early or late onset and including some with downregulated EBNA 2 and LMP 1, arose from post-germinal cells with randomly mutated or sterile IgH genotypes usually incompatible with B-cell survival in vivo.<br />Interpretation: PTLD can arise from a broad range of target B cells and not only from the pool of antigen-selected memory cells that EBV generally colonises in immunocompetent individuals. Tumour development seems frequently associated with the EBV-induced rescue and expansion of B cells that have failed the physiological process of germinal centre selection into memory. This finding shows an unexpected connection between pathogenesis of PTLD and that of EBV-positive Hodgkin's lymphoma, another B-cell malignancy of atypical post-germinal-centre cell origin.
- Subjects :
- Amino Acid Sequence
Base Sequence
Genotype
Herpesvirus 4, Human pathogenicity
Humans
Lymphoproliferative Disorders pathology
Molecular Sequence Data
Herpesvirus 4, Human genetics
Hodgkin Disease virology
Lymphoproliferative Disorders virology
Organ Transplantation
Postoperative Complications virology
Subjects
Details
- Language :
- English
- ISSN :
- 0140-6736
- Volume :
- 361
- Issue :
- 9353
- Database :
- MEDLINE
- Journal :
- Lancet (London, England)
- Publication Type :
- Academic Journal
- Accession number :
- 12547545
- Full Text :
- https://doi.org/10.1016/S0140-6736(03)12271-4