Jianli Lin1,2,3, Nana Huang1,3, Jing Li2,3, Xiaoyu Liu1,3, Qing Xiong4, Chengshen Hu1, Desheng Chen1, Lvxin Guan1, Kexin Chang1, Dan Li1, Stephen Kwok-Wing Tsui4, Nanshan Zhong2,5, Zhigang Liu1,5, Ping-Chang Yang1,6,5. 1. State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University School of Medicine, Shenzhen, China. 2. State Key Laboratory of Respiratory Disease, National Clinical Center for Respiratory Diseases, Guangzhou Institute of Respiratory Diseases, First Affiliated Hospital, Guangzhou Medical University, Guangzhou, China. 3. These authors contributed equally to this work. 4. School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, China. 5. Nanshan Zhong, Zhigang Liu and Ping-Chang Yang contributed equally to this article as lead authors and supervised the work. 6. Guangdong Provincial Key Laboratory of Regional Immunity and Diseases, Shenzhen, China.
Abstract
BACKGROUND AND AIMS: Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. METHODS: Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. RESULTS: High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. CONCLUSIONS: HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.
BACKGROUND AND AIMS: Neutrophilic inflammation is a hallmark of some specific asthma phenotypes; its aetiology is not yet fully understood. House dust mite (HDM) is the most common factor in the pathogenesis of airway inflammation. This study aims to elucidate the role of cross-antibodies against HDM-derived factors in the development of neutrophilic inflammation in the airway. METHODS: Blood samples were collected from asthma patients with chronic neutrophilic asthma for analysis of HDM-specific cross-reactive antibodies. The role of an antibody against HDM-derived enolase (EnoAb) in the impairment of airway epithelial barrier function and induction of airway inflammation was assessed in a cell culture model and an animal model. RESULTS: High similarity (72%) of the enolase gene sequences was identified between HDM and human. Serum EnoAb was detected in patients with chronic neutrophilic asthma. The EnoAb bound to airway epithelial cells to form complexes with enolase, which activated complement, impaired airway epithelial barrier functions and induced neutrophilic inflammation in the airway tissues. CONCLUSIONS: HDM-derived enolase can induce specific cross-antibodies in humans, which induce neutrophilic inflammation in the airway.