Allergic bronchopulmonary Aspergillosis patients’ serum can modulate Aspergillus-induced immune responses by increasing IL-6 and decreasing IL-5

Ref ID: 19366

Author:

K. L. Becker,1 K. Agarwal,2 M. G. Netea,3 S. N. Gaur,2
J. F. Meis,4 A. Chowdhary5 and F. L. van de Veerdonk3

Author address:

1Radboud University Nijmegen Medical Centre, the Netherlands;
2Department of Pulmonary Medicine, Vallabhbhai Patel Chest
Institute, University of Delhi, India; 3Department of Medicine,
Radboud University Nijmegen Medical Centre, the Netherlands;

Full conference title:

6th Trends in Medical Mycology 2013

Date: 11 October 2014

Abstract:

Objectives Allergic Bronchopulmonary Aspergillosis (ABPA) is a T
helper (Th) 2 mediated hypersensitivity reaction in the lung against
the species of the mould genus Aspergillus, most common of which is
A. fumigatus. It occurs most often in patients with asthma and cystic
fibrosis and has a high prevalence in India. We screened sera from
84 Indian patients with ABPA for cytokine and chemokine profiles
and performed functional stimulation assays to decipher the
immune-modulatory capacity of ABPA sera.
Methods 27 different cytokines were measured in the sera of 84
ABPA patients and 12 healthy controls (HC) from the same geo-
graphical area by a magnetic bead immunoassay. 17 ABPA patients
were treated with itraconazole whereas 67 did not receive antifungal
treatment. Peripheral blood mononuclear cells (PBMCs) of five
healthy volunteers were stimulated with Aspergillus conidia in the
presence of 40 individual ABPA sera and 12 HC sera. IL-6, TNFa, IL-
5, IL-13 and IFNc ELISA were performed on supernatants.
Results Cytokines derived from innate immune cells (IL-6, IL-1ra,
IL-12), Th2 cells (IL-4), Th1 cells (IFNc), hematopoietic cells (GM-
CSF, G-CSF) and the angiogenetic growth factor, VEGF were signifi-
cantly elevated in antifungal-naive ABPA sera compared to HC sera.
In contrast, TNFa or Eotaxin were not significantly different. Interest-
ingly, the concentrations of the elevated cytokines in ABPA sera
were at a normal level in all 17 patients treated with itraconazole.
Functional stimulation assays revealed a significantly higher Aspergillus
-induced IL-6 production in the presence of ABPA sera in all five
experiments with PBMCs from healthy volunteers, while Aspergillus-
induced TNFa was not modulated. IFNc was not modulated in these
functional assays, however IL-5 was significantly lower in 4 out of 5
PBMC experiments.
Conclusion We describe here in a large cohort of ABPA patients
that sera from patients with ABPA show an elevated proinflammato-
ry cytokine profile rather than the classical Th2 cytokine profile.
Increased serum concentrations could be restored to the level of
healthy controls through antifungal treatment with itraconazole,
suggesting a correlation of the fungal load with immune stimulation.
Moreover, the immunomodulatory capacity of sera from patients
with ABPA is characterised by increasing Aspergillus-induced IL-6
responses, but not TNF, and decreasing IL-5 production, which are
unexpected findings that need further investigation.

Abstract Number: NULL

Conference Year: 2013

Link to conference website: NULL

New link: NULL

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