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 Blood, 15 January 2008, Vol. 111, No. 2, pp. 534-536.
Prepublished online as a Blood First Edition Paper on October 23, 2007; DOI 10.1182/blood-2007-05-090928.

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CHEMOKINES, CYTOKINES, AND INTERLEUKINS

Brief Report

Polymorphisms in the chemokine (C-X-C motif) ligand 10 are associated with invasive aspergillosis after allogeneic stem-cell transplantation and influence CXCL10 epression in monocyte-derived dendritic cells

Markus Mezger1, Michael Steffens2, Melanie Beyer1, Carolin Manger1, Johannes Eberle1, Mohammad-Reza Toliat3, Thomas F. Wienker2, Per Ljungman4, Holger Hebart5, Hans Jürgen Dornbusch6, Hermann Einsele1, and Juergen Loeffler1

1 Julius-Maximilians-Universität Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany; 2 Institut für Medizinische Biometrie, Informatik, und Epidemiologie der Rheinischen Friedrich-Wilhelms-Universität, Bonn, Germany; 3 Cologne Centre for Genomics, Cologne, Germany; 4 Karolinska University Hospital/Huddinge, Stockholm, Sweden 5 Universitätsklinikum Tübingen, Medizinische Klinik II, Tübingen, Germany, and 6 Universitätsklinik für Kinder- und Jugendheilkunde, Graz, Austria

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.


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