Early stop polymorphism in human DECTIN-1 is associated with increased Candida 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, Mihai G Netea

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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.
Original languageEnglish
Pages (from-to)724-732
Number of pages9
JournalClinical Infectious Diseases
Volume49
Issue number5
DOIs
Publication statusPublished - 1 Sep 2009

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Hematopoietic Stem Cells
Candida
Hematopoietic Stem Cell Transplantation
Transplants
Candidemia
C-Type Lectins
Fluconazole
Immunocompromised Host
Hematologic Neoplasms
Fungi
Cytokines
Phenotype
Transplant Recipients
Incidence
Genes
dectin 1
Systemic candidiasis
Therapeutics

Keywords

  • adolescent
  • adult
  • aged
  • antifungal agents
  • Candida
  • candidiasis
  • female
  • fluconazole
  • hematopoietic stem cell transplantation
  • humans
  • immunocompromised host
  • male
  • membrane proteins
  • middle aged
  • nerve tissue proteins
  • opportunistic infections
  • polymorphism, genetic
  • retrospective studies
  • young adult

Cite this

Plantinga, T. S., van der Velden, W. J. F. M., Ferwerda, B., van Spriel, A. B., Adema, G., Feuth, T., ... 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, 49(5), 724-732. https://doi.org/10.1086/604714

Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients. / Plantinga, Theo S; van der Velden, Walter J F M; Ferwerda, Bart; van Spriel, Annemiek B; Adema, Gosse; Feuth, Ton; Donnelly, J Peter; Brown, Gordon D; Kullberg, Bart-Jan; Blijlevens, Nicole M A; Netea, Mihai G.

In: Clinical Infectious Diseases, Vol. 49, No. 5, 01.09.2009, p. 724-732.

Research output: Contribution to journalArticle

Plantinga, TS, van der Velden, WJFM, Ferwerda, B, van Spriel, AB, Adema, G, Feuth, T, Donnelly, JP, Brown, GD, Kullberg, B-J, Blijlevens, NMA & Netea, MG 2009, 'Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients', Clinical Infectious Diseases, vol. 49, no. 5, pp. 724-732. https://doi.org/10.1086/604714
Plantinga, Theo S ; van der Velden, Walter J F M ; Ferwerda, Bart ; van Spriel, Annemiek B ; Adema, Gosse ; Feuth, Ton ; Donnelly, J Peter ; Brown, Gordon D ; Kullberg, Bart-Jan ; Blijlevens, Nicole M A ; Netea, Mihai G. / Early stop polymorphism in human DECTIN-1 is associated with increased Candida colonization in hematopoietic stem cell transplant recipients. In: Clinical Infectious Diseases. 2009 ; Vol. 49, No. 5. pp. 724-732.
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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.",
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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 - 2009/9/1

Y1 - 2009/9/1

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.

AB - 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.

KW - adolescent

KW - adult

KW - aged

KW - antifungal agents

KW - Candida

KW - candidiasis

KW - female

KW - fluconazole

KW - hematopoietic stem cell transplantation

KW - humans

KW - immunocompromised host

KW - male

KW - membrane proteins

KW - middle aged

KW - nerve tissue proteins

KW - opportunistic infections

KW - polymorphism, genetic

KW - retrospective studies

KW - young adult

U2 - 10.1086/604714

DO - 10.1086/604714

M3 - Article

VL - 49

SP - 724

EP - 732

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 5

ER -