Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26

Sabrine Louhaichi; Mariem Salhi; Anissa Berraïes; Besma Hamdi; Jamel Ammar; Kamel Hamzaoui; Agnès Hamzaoui; Sabrine Louhaichi; Mariem Salhi; Anissa Berraïes; Besma Hamdi; Jamel Ammar; Kamel Hamzaoui; Agnès Hamzaoui

doi:10.3934/Allergy.2018.1.10

AIMS Allergy and Immunology

2018, Volume 2, Issue 1: 10-23. doi: 10.3934/Allergy.2018.1.10

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Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26

1.
Unit Research 12SP15 “Homeostasis and Molecular Dysfunction in the lung” Abderrahman Mami Hospital, Pavillon B, Ariana, Tunisia
2.
Université de Tunis El Manar, Faculty of Medicine of Tunis, Tunisia
3.
Division of Paediatric Respiratory Diseases, Pavillon B, A. Mami Hospital, Ariana, Tunisia

Received: 10 January 2018 Accepted: 07 March 2018 Published: 09 March 2018

Background: Asthma is an immunological disorder in which T helper 2 (Th2)-type cells and inflammatory cytokines have a prominent role in its pathogenesis. B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. Objective: In the present study of asthmatic patients we measured the soluble isoforms of BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) in induced sputum fluid with the aim to evaluate their utility as responsible for exacerbation. Methods: Eighty patients with asthma and 30 healthy controls (HC) were included in the study. Sputum fluid concentrations of sBTLA, sCTLA-4 and sPD-1 were measured with ELISA. Comparisons were made with Mann-Whitney U test and correlations with IL-17, IL-26 levels and FEV1 (%) were assessed with Spearman’s Rank correlation test. Results: sBTLA levels were significantly higher in the severe and moderate asthmatic patients compared to healthy controls. Significant differences were observed between severe and moderate asthmatics (p < 0.0001). No significant differences were found between mild asthmatics and healthy controls (p = 0.799). Soluble PD-1 levels were higher in severe and moderate asthmatic patients compared to HC and no significant difference was observed between these two asthmatic groups (p = 0.124). Mild asthmatics and control subjects expressed similar sPD-1 levels (p = 0.856). Soluble CTLA-4 was exclusively expressed in certain severe asthmatic patients. IL-17 inflammatory cytokine was significantly correlated with BTLA and sPD-1. IL-17 and IL-26 cytokines were highly expressed in sputum asthmatic groups compared to sputum from HC. Severe asthmatic group was characterized by the highest levels of both IL-17 and IL-26 mediators. Soluble BTLA correlates positively with IL-17 (r = 0.817; p < 0.0001) and IL-26 (r = 0.805; p < 0.0001) inflammatory cytokines. IL-17 and IL-26 levels were associated with the asthma clinical severity from severe to mild asthma (p < 0.0001). The inflammatory cytokines IL-17 and IL-26 were positively correlated with the percentages of macrophages, PNN and FEV1 (%). Conclusion: Here, we provide the first report on the increased expression of sBTLA and sPD-1 in induced sputum of severe asthmatics. IL-26 and IL-17 appeared as a novel proinflammatory axis. Both sBTLA and sPD-1 might be involved in the pathogenesis of asthma and were associated with a poor prognosis.
- severe asthma,
- induced sputum,
- sBTLA,
- sCTLA4,
- sPD-1,
- IL-17,
- IL-26
Citation: Sabrine Louhaichi, Mariem Salhi, Anissa Berraïes, Besma Hamdi, Jamel Ammar, Kamel Hamzaoui, Agnès Hamzaoui. Co-inhibitory receptors in female asthmatic patients: Correlation with IL-17 and IL-26[J]. AIMS Allergy and Immunology, 2018, 2(1): 10-23. doi: 10.3934/Allergy.2018.1.10

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Abstract

Background: Asthma is an immunological disorder in which T helper 2 (Th2)-type cells and inflammatory cytokines have a prominent role in its pathogenesis. B- and T-lymphocyte attenuator (BTLA), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed death 1 (PD-1) are co-inhibitory receptors that regulate T cell activation. Objective: In the present study of asthmatic patients we measured the soluble isoforms of BTLA (sBTLA), CTLA-4 (sCTLA-4) and PD-1 (sPD-1) in induced sputum fluid with the aim to evaluate their utility as responsible for exacerbation. Methods: Eighty patients with asthma and 30 healthy controls (HC) were included in the study. Sputum fluid concentrations of sBTLA, sCTLA-4 and sPD-1 were measured with ELISA. Comparisons were made with Mann-Whitney U test and correlations with IL-17, IL-26 levels and FEV1 (%) were assessed with Spearman’s Rank correlation test. Results: sBTLA levels were significantly higher in the severe and moderate asthmatic patients compared to healthy controls. Significant differences were observed between severe and moderate asthmatics (p < 0.0001). No significant differences were found between mild asthmatics and healthy controls (p = 0.799). Soluble PD-1 levels were higher in severe and moderate asthmatic patients compared to HC and no significant difference was observed between these two asthmatic groups (p = 0.124). Mild asthmatics and control subjects expressed similar sPD-1 levels (p = 0.856). Soluble CTLA-4 was exclusively expressed in certain severe asthmatic patients. IL-17 inflammatory cytokine was significantly correlated with BTLA and sPD-1. IL-17 and IL-26 cytokines were highly expressed in sputum asthmatic groups compared to sputum from HC. Severe asthmatic group was characterized by the highest levels of both IL-17 and IL-26 mediators. Soluble BTLA correlates positively with IL-17 (r = 0.817; p < 0.0001) and IL-26 (r = 0.805; p < 0.0001) inflammatory cytokines. IL-17 and IL-26 levels were associated with the asthma clinical severity from severe to mild asthma (p < 0.0001). The inflammatory cytokines IL-17 and IL-26 were positively correlated with the percentages of macrophages, PNN and FEV1 (%). Conclusion: Here, we provide the first report on the increased expression of sBTLA and sPD-1 in induced sputum of severe asthmatics. IL-26 and IL-17 appeared as a novel proinflammatory axis. Both sBTLA and sPD-1 might be involved in the pathogenesis of asthma and were associated with a poor prognosis.

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