Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 expression in monocyte-derived dendritic cells.
Patients after allogeneic stem-cell transplantation (alloSCT) have an increased risk for invasive aspergillosis (IA). Here, recipients of an allograft with IA (n=81) or without IA (n=58) were screened for 84 single nucleotide polymorphisms in 18 immune relevant genes. We found 3 markers in chemokine (C-X-C motif) ligand 10 (CXCL10, 4q21, 11,101 C>T, P=.007; 1642 C<G, P=.003; -1101 A<G, P=.001) significantly associated with an increased risk of developing IA. Furthermore, immature dendritic cells (iDCs) exposed to Aspergillus fumigatus germlings showed markedly higher CXCL10 expression, if carrying the wild type genotype, compared with the "CGAG" high risk haplotype. In addition, serum from patients with proven/probable IA showed increased serum levels of CXCL10, compared with immunocompromised patients without IA. Thus, polymorphisms in CXCL10 determine chemokine secretion by iDCs upon exposure to A fumigatus and most likely thereby genetically determine the risk of IA after alloSCT.
Mezger
Markus
M
Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II, Germany.
Steffens
Michael
M
Beyer
Melanie
M
Manger
Carolin
C
Eberle
Johannes
J
Toliat
Mohammad-Reza
MR
Wienker
Thomas F
TF
Ljungman
Per
P
Hebart
Holger
H
Dornbusch
Hans Jürgen
HJ
Einsele
Hermann
H
Loeffler
Juergen
J
D001228:Aspergillosis / Q000097:blood / Q000235:genetics* / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000097:blood / Q000235:genetics* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D019337:Hematologic Neoplasms / Q000097:blood / Q000235:genetics / Q000276:immunology; D006801:Humans; D008297:Male; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000276:immunology; D012307:Risk Factors; D033581:Stem Cell Transplantation; D014184:Transplantation, Homologous
C114753:CXCL10 protein, human; D054357:Chemokine CXCL10