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Tijdschrift voor kindergeneeskunde

, Volume 70, Issue 4, pp 96–101 | Cite as

Serie wetensc happelijk onderzoek

Infecties met dna-virussen na stamceltransplantatie: virologische en immunologische diagnostiek en therapie
  • J. M. Vossen
  • M. J. D. van Tol
Artikelen
  • 11 Downloads

Samenvatting

Na allogene hemopoëtische stamceltransplantatie volgt een maandenlange periode van immuundeficiëntie bij de ontvanger. Deze immuundeficiëntie is zowel ernstiger als langer bij de ontvanger van een T-cel gedepleteerd transplantaat van een andere donor dan een hla-identieke broer of zuster. In het afgelopen decennium, waarin progressief meer transplantaties van dit type werden verricht, werd een sterke toename gezien van vaak dodelijk verlopende infecties met ebv en adenovirussen. Deze dna-virussen worden bij een immuuncompetent persoon in latente staat gehouden door specifieke T- en B-cellulaire immuunreacties. Omdat deze immuunreacties na een T-cel gedepleteerde transplantatie bij de ontvanger ontbreken en de de novo ontwikkeling ervan vele maanden in beslag neemt, leiden reactivaties c.q. infecties met die dna-virussen vaak tot een ernstige ziekte met dodelijke afloop.

Een van de onderzoekslijnen van de subafdeling ihoba (Immunologie/Hematologie/Oncologie/Beenmergtransplantatie/Auto-immuunziekten) richt zich op snelle en zeer gevoelige diagnostiek van virusreactivatie, op longitudinaal en specifiek meten van antivirale immunologische afweer en op tijdige antivirale therapie. Het onderzoek gebeurt in nauwe samenwerking met de afdeling Medische Virologie en met pediatrische transplantatiecentra in Nederland en andere landen van Europa.

In het kader van dit onderzoek worden nieuwe, uiterst gevoelige technieken, ontwikkeld voor diagnostiek, zoals rq-pcr (real-time quantitative polymerase chain reaction) en tetramere hla-peptidecomplexen voor het kwantificeren van virusspecifieke T-cellen, en specifieke therapieën, zoals monoklonale antistoffen en virusspecifieke cytotoxische T-cellen, uitgetest.

Summary

The recipient of an allogeneic haematopoietic stem cell graft suffers from an immune deficiency, which lasts several months after transplantation. The immune deficiency is more severe as well as prolonged following a graft from an other donor than an hla-identical sibling and after T-cell depletion of the graft. The latter type of transplantations has been performed with increasing frequency in the past decade. This coincided with an increasing number of frequently lethal infections with ebv and adenoviruses. These dna-viruses are kept in a state of latency by specific T- and B-cellular immune reactions, in case of an immunocompetent host. Because such immunological reactions are absent in the recipient shortly after a T-cell depleted graft, and because the recovery of these reactions from the outgrowth of precursor T- and B-cells of donor origin takes several months, dna-viruses get the opportunity to expand and cause severe infections.

Of the different research topics of the department of immunology, haemato-oncology, bone marrow transplantation and autoimmune diseases (ihoba) one focuses on rapid and sensitive virological diagnosis and on follow-up of specific antiviral immunity in the graft recipient. The aim of these longitudinal investigations is to administer pre-emptive antiviral treatment, if necessary. This research programme is carried out in close co-operation with the department of Medical Virology in Leiden and with paediatric transplant centres in the Netherlands and other countries of Europe. For this purpose a novel, extremely sensitive technique, i.e. a real-time quantitative polymerase chain reaction (rq-pcr) for the diagnosis of the viral (dna) load in plasma has been developed. Besides that, tetrameric hla-peptide complexes for the quantification of virus-specific T-cells in the blood of the host will be tested, and specific antiviral therapy, using monoclonal antibodies and virus-specific cytotoxic T-cells will be tried.

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Copyright information

© Bohn Stafleu van Loghum 2002

Authors and Affiliations

  • J. M. Vossen
    • 1
  • M. J. D. van Tol
  1. 1.

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