Published ahead of print on March 16, 2006, doi:10.1164/rccm.200508-1271OC Am. J. Respir. Crit. Care Med., Volume 173, Number 12, June 2006, 1370-1376 A more recent version of this article appeared on June 15, 2006
Submitted on August 16, 2005 Chemokines Indicate Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis PatientsDominik Hartl1*,1 Children's Hospital of the Ludwig-Maximilians-University of Munich, Munich, Germany, 2 Children's Hospital of the Ludwig-Maximilians-University of Munich, Munich, Germany; Department of Pediatrics, University Hospital of Berne, Berne, Switzerland, 3 Department of Pneumology, University Hospital, Medical Center, Freiburg, Germany, 4 Clinical Cooperation Group "Pediatric Immune Regulation" of Childrens' Hospital of the Ludwig-Maximilians-University and GSF National Research Center for Environment and Health, Munich, Germany * To whom correspondence should be addressed. E-mail: dominic.hartl{at}med.uni-muenchen.de.
Rationale
Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a Th2 immune response. Mouse models suggest a critical role for the Th2 chemokines thymus- and activation-regulated chemokine (TARC) and macrophage-derived chemokine (MDC) in ABPA.
Objectives
To determine whether serum levels of TARC and MDC characterize ABPA in cystic fibrosis (CF) patients. Furthermore, to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in CF patients.
Methods
Levels of TARC and MDC and levels of Th1 (IL-12 and IFN- Key words: Allergic bronchopulmonary aspergillosis, ABPA, TARC, chemokines, cystic fibrosis
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) and Th2 (IL-4, IL-5 and IL-13) cytokines were analyzed in serum of 16 CF patients with ABPA, 6 non-CF asthmatic patients with ABPA, 13 CF patients colonized with A. fumigatus, 6 CF patients sensitized to A. fumigatus, 12 atopic CF patients and 13 non-CF atopic controls by ELISA. The longitudinal course of TARC, MDC and IgE levels was assessed during ABPA episodes.
Results
ABPA patients had significantly higher serum levels of TARC compared to the other patient groups, while cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in CF patients more clearly than IgE levels. In CF ABPA patients, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4.
Conclusions
Serum levels of TARC differentiate CF or asthma patients with ABPA from CF patients colonized with or sensitized to A. fumigatus, atopic CF patients and atopic controls. Longitudinally, levels of TARC clearly indicate ABPA exacerbations, suggesting TARC as a marker for identification and monitoring of ABPA in CF patients.
