title: 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.
abstract: 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.
authors.affiliation: Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Mezger
authors.forename: Michael
authors.initials: M
authors.lastname: Steffens
authors.forename: Melanie
authors.initials: M
authors.lastname: Beyer
authors.forename: Carolin
authors.initials: C
authors.lastname: Manger
authors.forename: Johannes
authors.initials: J
authors.lastname: Eberle
authors.forename: Mohammad-Reza
authors.initials: MR
authors.lastname: Toliat
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Wienker
authors.forename: Per
authors.initials: P
authors.lastname: Ljungman
authors.forename: Holger
authors.initials: H
authors.lastname: Hebart
authors.forename: Hans Jürgen
authors.initials: HJ
authors.lastname: Dornbusch
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: 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
chemical_list: C114753:CXCL10 protein, human; D054357:Chemokine CXCL10