The CD14 (\u2212159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

J J Nieto-Fontarigo,A Casas-Fernández,F J Salgado,F J González-Barcala,F J González-Barcala,F J González-Barcala,M Nogueira,M Á García-González,M J Cruz,M J Gómez-Conde,M E San-José,L Valdés-Cuadrado,L Valdés-Cuadrado,P Arias

doi:10.1038/s41598-018-20483-1

Abstract

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult Caucasians.

Highlights

During asthma attacks allergens trigger lung epithelial cells to release cytokines (e.g., Thymic stromal lymphopoietin (TSLP), Interleukin (IL)-33, IL-25) that activate innate leukocytes and drive the differentiation of allergen-specific T helper (TH)[2] lymphocytes[1]
forced expiratory volume in 1 second (FEV1) (%) and FEV1/Forced vital capacity (FVC) ratio (%) values are described in Table 1, showing decreased levels in moderate-severe allergic asthmatics (MSAA) compared to intermittent-mild allergic asthmatics (IMAA) (Table 1)
Since activation of eosinophils and macrophages has been associated to enhanced neuron-specific enolase (NSE) levels under some pathological conditions[26,27], we undertook the measurement of this enzyme in serum samples

Summary

Introduction

During asthma attacks allergens trigger lung epithelial cells to release cytokines (e.g., Thymic stromal lymphopoietin (TSLP), Interleukin (IL)-33, IL-25) that activate innate leukocytes and drive the differentiation of allergen-specific T helper (TH)[2] lymphocytes[1]. Different works have confirmed these results[18,19], while the C allele has been associated with high IgE levels, atopy and asthma[15,17,20]. Allergic asthma enhances the number of peripheral blood monocytes, but causes a reduction of mCD14 in these cells.

Results

Conclusion