Early Stop Polymorphism in Human DECTIN-1 Is Associated with Increased Candida Colonization in Hematopoietic Stem Cell Transplant Recipients
TS Plantinga, WJFM Van Der Velden… - Clinical Infectious …, 2009 - academic.oup.com
TS Plantinga, WJFM Van Der Velden, B Ferwerda, AB Van Spriel, G Adema, T Feuth…
Clinical Infectious Diseases, 2009•academic.oup.comBackground. 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 …
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 …
Abstract
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.
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