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Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients.
Clin Infect Dis. 2009 Sep 01; 49(5):724-32.CI

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-beta-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.

Authors+Show Affiliations

Departments of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19614557

Citation

Plantinga, Theo S., et al. "Early Stop Polymorphism in Human DECTIN-1 Is Associated With Increased Candida Colonization in Hematopoietic Stem Cell Transplant Recipients." Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, vol. 49, no. 5, 2009, pp. 724-32.
Plantinga TS, van der Velden WJ, Ferwerda B, et al. Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2009;49(5):724-32.
Plantinga, T. S., van der Velden, W. J., Ferwerda, B., van Spriel, A. B., Adema, G., Feuth, T., Donnelly, J. P., Brown, G. D., Kullberg, B. J., Blijlevens, N. M., & Netea, M. G. (2009). Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America, 49(5), 724-32. https://doi.org/10.1086/604714
Plantinga TS, et al. Early Stop Polymorphism in Human DECTIN-1 Is Associated With Increased Candida Colonization in Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2009 Sep 1;49(5):724-32. PubMed PMID: 19614557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early stop polymorphism in human DECTIN-1 is associated with increased candida colonization in hematopoietic stem cell transplant recipients. AU - Plantinga,Theo S, AU - van der Velden,Walter J F M, AU - Ferwerda,Bart, AU - van Spriel,Annemiek B, AU - Adema,Gosse, AU - Feuth,Ton, AU - Donnelly,J Peter, AU - Brown,Gordon D, AU - Kullberg,Bart-Jan, AU - Blijlevens,Nicole M A, AU - Netea,Mihai G, PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2009/9/30/medline SP - 724 EP - 32 JF - Clinical infectious diseases : an official publication of the Infectious Diseases Society of America JO - Clin. Infect. Dis. VL - 49 IS - 5 N2 - 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-beta-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. SN - 1537-6591 UR - https://www.unboundmedicine.com/medline/citation/19614557/Early_stop_polymorphism_in_human_DECTIN_1_is_associated_with_increased_candida_colonization_in_hematopoietic_stem_cell_transplant_recipients_ L2 - https://academic.oup.com/cid/article-lookup/doi/10.1086/604714 DB - PRIME DP - Unbound Medicine ER -