L Antunes1, A P Duarte de Souza2, P D de Araújo1, L A Pinto3, M H Jones3, R T Stein3, P M Pitrez4. 1. Laboratory of Clinical and Experimental Immunology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. 2. Laboratory of Clinical and Experimental Immunology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. Electronic address: ana.duarte@pucrs.br. 3. Laboratory of Respiratory Physiology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil. 4. Laboratory of Pediatric Respirology, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Infant Center, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil; Institute of Biomedical Research, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Brazil.
Abstract
BACKGROUND: Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in human asthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls. METHODS: Children with asthma (n=136) (non-severe and STRA) from a referral centre and healthy controls (n=40) were recruited. Peripheral blood mononuclear cells were isolated, stained with anti-CD3 and anti-iNKT (Vα24Jα18), and analysed through flow cytometry. Atopic status was defined by measuring specific IgE in serum. Airway inflammation was assessed by induced sputum. RESULTS: Children with asthma presented an increased frequency of CD3+iNKT+ cells (median 0.38% IQR 0.18-1.9), compared to healthy controls (median 0.26% IQR 0.10-0.43) (p=0.025). Children with STRA also showed an increased frequency of iNKT cells (1.5% IQR 1.05-2.73) compared to healthy controls and non-severe asthmatic children (0.35% IQR 0.15-1.6; p=0.002). The frequency of iNKT cells was not different between atopic and non-atopic children. In addition, iNKT cells were not associated with any inflammatory pattern of induced sputum studied. CONCLUSION: Our data suggests that iNKT cells play a role in paediatric asthma, which is also associated with the severity of disease, but independent of the atopic status.
BACKGROUND: Invariant natural killer T (iNKT) cells play complex functions in the immune system, releasing both Th1 and Th2 cytokines. The role of iNKT cells in humanasthma is still controversial and never described in severe therapy-resistant asthma in children. The objective of this work was to analyse iNKT frequency in peripheral blood of children with severe therapy-resistant asthma (STRA), compared to children with milder asthma and healthy controls. METHODS:Children with asthma (n=136) (non-severe and STRA) from a referral centre and healthy controls (n=40) were recruited. Peripheral blood mononuclear cells were isolated, stained with anti-CD3 and anti-iNKT (Vα24Jα18), and analysed through flow cytometry. Atopic status was defined by measuring specific IgE in serum. Airway inflammation was assessed by induced sputum. RESULTS:Children with asthma presented an increased frequency of CD3+iNKT+ cells (median 0.38% IQR 0.18-1.9), compared to healthy controls (median 0.26% IQR 0.10-0.43) (p=0.025). Children with STRA also showed an increased frequency of iNKT cells (1.5% IQR 1.05-2.73) compared to healthy controls and non-severe asthmatic children (0.35% IQR 0.15-1.6; p=0.002). The frequency of iNKT cells was not different between atopic and non-atopic children. In addition, iNKT cells were not associated with any inflammatory pattern of induced sputum studied. CONCLUSION: Our data suggests that iNKT cells play a role in paediatric asthma, which is also associated with the severity of disease, but independent of the atopic status.