Genetic variants of dectin1 and susceptibility to infections with Candidaspp.
Abstract number: O298
Plantinga T.S., Johnson M.D., van der Velden W., Rosentul D., Giamarellos-Bourboulis E.J., Ferwerda B., Smith P.B., Alexander B.D., Joosten L.A., van der Meer J., Donnelly P., Perfect J.R., Blijlevens N., Kullberg B.J., Netea M.G.
Objectives: Systemic and oropharyngeal candidiasis represent a cause of high morbidity especially in immunocompromised hosts, with risk varying significantly between individuals. Recognition of Candida albicans is mediated through pattern recognition receptors such as the b-glucan receptor dectin-1. We recently identified an early stopcodon single nucleotide polymorphism (SNP) Y238X in dectin-1 that is associated with the loss of b-glucan recognition (N Engl J Med. 2009;361:17607).
Methods: We assessed whether the presence of the dectin-1 Y238X SNP was associated with an increased susceptibility to Candida infections in several clinical settings: i. in 365 American and Dutch patients with candidaemia compared to 351 non-infected American and Dutch controls; ii. in 142 Dutch patients undergoing haematopoietic stem cell transplantation (HSCT); and iii. in 170 Greek HIV-infected patients.
Results: Dectin-1 Y238X SNP was strongly correlated with Candida colonization in HSCT patients: 34% of the individuals bearing the wild-type allele were colonized with Candida, compared to 85% of the individuals bearing the mutant allele (p < 0.005), necessitating more frequent use of fluconazole treatment (p < 0.01). Functional assays demonstrated a loss-of-function phenotype of the SNP, as shown by the decreased cytokine production by immune cells bearing this SNP. In contrast, the dectin-1 Y238X SNP did not influence susceptibility to candidaemia or that of oropharyngeal candidiasis in HIV-infected patients.
Conclusions: The dectin-1 Y238X SNP is non-redundant for the recognition of C. albicans, and influences mucosal Candida colonization. In contrast, lack of functional dectin-1 is not accompanied by an increased susceptibility to bloodstream Candida infections.
|Session name:||Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases|
|Location:||Vienna, Austria, 10 - 13 April 2010|
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