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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients
Clinical Infectious Diseases, Volume 49, No. 5, Year 2009
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Description
Background. Intensive treatment of hematological malignancies with hematopoietic stem cell transplantation (HSCT) is accompanied by a high incidence of opportunistic invasive fungal infection, but individual risk varies significantly. Dectin-1, a C-type lectin that recognizes l, 3-β-glucans from fungal pathogens, including Candida species, is involved in the initiation of the immune response against fungi. Methods. Screening for the DECTIN-1 Y238X polymorphism within a group of 142 patients undergoing HSCT was correlated with Candida colonization and candidemia. Furthermore, functional studies were performed on the consequences of the polymorphism. Results. Patients bearing the Y238X polymorphism in the DECTIN-1 gene were more likely to be colonized with Candida species, compared with patients bearing wild-type DECTIN-1, necessitating more frequent use of fluconazole in the prevention of systemic Candida infection. Functional assays demonstrated a loss-of-function phenotype of the polymorphism, as shown by the decreased cytokine production by immune cells bearing this polymorphism. Conclusions. The Y238X polymorphism is associated with increased oral and gastrointestinal colonization with Candida species. This suggests a crucial role played by dectin-1 in the mucosal antifungal mechanisms in immunocompromised hosts. The finding that DECTIN-1 polymorphisms rendered HSCT recipients at increased risk for fungal complications may contribute to the selection of high-risk patients who should be considered for antifungal prophylaxis to prevent systemic candidiasis. © 2009 by the Infectious Diseases Society of America. All right resserved.
Authors & Co-Authors
Plantinga, Theo S.
Netherlands, Nijmegen
Radboud University Medical Center
Van Der Velden, Walter J.F.M.
Netherlands, Nijmegen
Radboud University Medical Center
Ferwerda, Bart
Netherlands, Nijmegen
Radboud University Medical Center
Van Spriel, Annemiek B.
Netherlands, Nijmegen
Radboud University Medical Center
Adema, Gosse J.
Netherlands, Nijmegen
Radboud University Medical Center
Feuth, Ton
Netherlands, Nijmegen
Radboud University Medical Center
Peter Donnelly, J.
Netherlands, Nijmegen
Radboud University Medical Center
Brown, Gordon D.A.
South Africa, Cape Town
University of Cape Town
Kullberg, Bart Jan
Netherlands, Nijmegen
Radboud University Medical Center
Blijlevens, Nicole M.A.
Netherlands, Nijmegen
Radboud University Medical Center
Netea, Mihai Gheorghe
Netherlands, Nijmegen
Radboud University Medical Center
Statistics
Citations: 247
Authors: 11
Affiliations: 2
Identifiers
Doi:
10.1086/604714
ISSN:
10584838
Research Areas
Genetics And Genomics
Health System And Policy
Study Design
Cohort Study