Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis.
BACKGROUND
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.


OBJECTIVE
To determine whether serum levels of TARC and MDC characterize ABPA in patients with cystic fibrosis (CF) and to examine longitudinally if levels of TARC and MDC indicate ABPA exacerbations in patients with CF.


METHODS
Levels of TARC and MDC and levels of Th1 (IL-12 and IFN-gamma) and Th2 (IL-4, IL-5, and IL-13) cytokines were analyzed in serum of 16 patients with CF with ABPA, six non-CF patients with asthma with ABPA, 13 patients with CF colonized with Aspergillus fumigatus, six patients with CF sensitized to A. fumigatus, 12 atopic patients with CF, and 13 non-CF atopic control subjects by ELISA. The longitudinal course of TARC, MDC, and IgE levels was assessed during ABPA episodes.


RESULTS
Patients with ABPA had significantly higher serum levels of TARC compared with the other patient groups. Cytokine levels did not differ among the patient groups. Longitudinally, levels of TARC indicated ABPA exacerbations in patients with CF more clearly than IgE levels. In patients with CF and ABPA, levels of TARC correlated positively with specific IgE to A. fumigatus and rAsp f4.


CONCLUSIONS
Serum levels of TARC differentiate patients with CF or patients with asthma with ABPA from patients with CF colonized with or sensitized to A. fumigatus, atopic patients with CF, and atopic control subjects. Longitudinally, levels of TARC indicate ABPA exacerbations, suggesting TARC as a marker for identification and monitoring of ABPA in patients with CF.
Hartl
Dominik
D
Department of Pediatrics, University Hospital of Berne, Switzerland. dominic.hartl@med.uni-muenchen.de
Latzin
Philipp
P
Zissel
Gernot
G
Krane
Markus
M
Krauss-Etschmann
Susanne
S
Griese
Matthias
M
D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000097:blood; D052179:Antigens, Plant; D001229:Aspergillosis, Allergic Bronchopulmonary / Q000097:blood / Q000175:diagnosis*; D001232:Aspergillus fumigatus / Q000276:immunology / Q000302:isolation & purification; D001249:Asthma / Q000097:blood / Q000150:complications; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC / Q000097:blood*; D002648:Child; D003550:Cystic Fibrosis / Q000150:complications*; D005260:Female; D005656:Fungal Proteins / Q000097:blood; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D018793:Interleukin-13 / Q000097:blood; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008137:Longitudinal Studies; D008264:Macrophages / Q000473:pathology*; D008297:Male; D013183:Sputum / Q000382:microbiology
D000485:Allergens; D052179:Antigens, Plant; C115316:Asp f 4 allergen; C106230:CCL17 protein, human; C515482:CCL22 protein, human; C515483:Ccl22 protein, mouse; D054414:Chemokine CCL17; D054422:Chemokine CCL22; D019742:Chemokines, CC; D005656:Fungal Proteins; D018793:Interleukin-13; D015848:Interleukin-5; D018664:Interleukin-12; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma