Journal Article

Early Stop Polymorphism in Human DECTIN-1 Is Associated with Increased <i>Candida</i> Colonization in Hematopoietic Stem Cell Transplant Recipients

Theo S. Plantinga, Walter J. F. M. van der Velden, Bart Ferwerda, Annemiek B. van Spriel, Gosse Adema, Ton Feuth, J. Peter Donnelly, Gordon D. Brown, Bart-Jan Kullberg, Nicole M. A. Blijlevens and Mihai G. Netea

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 49, issue 5, pages 724-732
Published in print September 2009 | ISSN: 1058-4838
Published online September 2009 | e-ISSN: 1537-6591 | DOI: https://dx.doi.org/10.1086/604714
Early Stop Polymorphism in Human DECTIN-1 Is Associated with Increased Candida Colonization in Hematopoietic Stem Cell Transplant Recipients

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  • Infectious Diseases
  • Immunology
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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 1,3-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.

Journal Article.  4152 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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