The incidence of acute graft-versus-host disease increases with Candida colonization depending the dectin-1 gene status.
Dectin-1 plays an important role in antifungal immunity. The dectin-1 Y238X polymorphism, which results in decreased Th17 responses, is associated with increased Candida colonization of stem cell transplantation (SCT) recipients. In this study we found no impact of the polymorphism on the incidence of graft-versus-host disease (GvHD), or on disease-free and overall survival in these SCT recipients. However, patients from patient-donor pairs bearing the wild-type allele who where colonized with Candida had a significant increased incidence of acute GvHD compared to non-colonized patients (OR=2.6, P=0.04). The fact that this was not the case in patients from pairs with the Y238X polymorphism (OR=1.2, ns) suggests that despite increased colonization defective dectin-1 signaling might have prevented an impact of Candida colonization on the incidence of acute GvHD to occur. These are the first human data showing a role for Candida in the pathogenesis of acute GvHD. The mechanism could involve C-type lectin receptor mediated Th17 responses.
van der Velden
Walter J F M
WJ
Department of Hematology, Radboud University Nijmegen Medical Center, HB Nijmegen, The Netherlands. w.vandervelden@hemat.umcn.nl
Plantinga
Theo S
TS
Feuth
Ton
T
Donnelly
J Peter
JP
Netea
Mihai G
MG
Blijlevens
Nicole M A
NM
D000293:Adolescent; D000328:Adult; D000368:Aged; D002175:Candida / Q000502:physiology; D002177:Candidiasis / Q000276:immunology*; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D020022:Genetic Predisposition to Disease; D006086:Graft vs Host Disease / Q000453:epidemiology* / Q000235:genetics / Q000382:microbiology; D006801:Humans; D015994:Incidence; D037181:Lectins, C-Type; D008297:Male; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D012307:Risk Factors; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D055815:Young Adult; D000099181:Dectin-1
D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1