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Research Article Open access CC BY 4.0

CTLA4 Expression in Childhood Asthma and the Effect of Treatment with Inhaled Corticosteroid and Leukotriene Receptor Antagonist

Vojko Berce, Carina E. P. Kozmus, Uroš Potočnik

Annual Research & Review in Biology · pp. 1–13 · Published 22 Apr 2016

10.9734/ARRB/2016/24564

Abstract

Aims: Cytotoxic T lymphocyte antigen 4 (CTLA4), an important regulatory molecule in the process of antigen presentation, was previously associated with the pathogenesis of autoimmune diseases and asthma. Therefore, the goal of our study was to determine the expression of CTLA4 in asthmatics, and the effect of CTLA4 CT60 genotype and antiasthmatic treatment on CTLA4 expression. Study Design:  We analyzed a case-control cohort of 229 children with mild to moderate persistent asthma. Blood samples were collected before treatment from 229 asthmatics, with matching samples obtained 4-6 weeks after treatment with inhaled corticosteroid (ICS) in 69 subjects and after treatment with leukotriene receptor antagonist (LTRA) in 105 subjects. Place and Duration of Study: Department of Pediatric Medicine, General Hospital Murska Sobota and University Medical Centre Maribor between January 2008 and May 2012. Methodology: We measured and compared CTLA4 expression in blood leukocytes of healthy controls and children with persistent asthma by qPCR and determined CTLA4 CT60 genotype by High Resolution Melting analysis. We further analyzed how antiasthmatic treatment with ICS or LTRA affected CTLA4 expression. Results: Median relative expression of full length CTLA4 (flCTLA4) isoform in asthmatics was 0.440±0.425, compared to 1.000±0.738 in controls (corrected P<.0001), and of soluble CTLA4 (sCTLA4) isoform in asthmatics was 0.580±0.468 compared to 1.040±1.080 in controls (corrected P<.0001). After ICS therapy the median relative expression of sCTLA4 significantly increased only in asthmatics with A allele, from 0.400±0.258 to 0.710±0.608 (corrected P=.0146). On the other hand, after LTRA therapy the median relative expression of sCTLA4 decreased only in asthmatics with A allele from 0.450±0.410 to 0.300±0.300 (corrected P=0.0006). Conclusion: We show that CTLA4 expression is decreased in asthmatic subjects. ICS and LTRA treatments, dependent on CTLA4 CT60 genotype, caused opposite effects on sCTLA4 expression, suggesting both drugs differently affect molecular pathways of antigen presentation during their action.

Antigen presentation blood leukocytes CTLA4 isoforms CTLA4 CT60 polymorphism antiasthmatic treatment asthma pathogenesis.

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