{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:01:40Z","timestamp":1787583700009,"version":"build-2736575974"},"reference-count":48,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011892","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8N0391"],"award-info":[{"award-number":["CMRPG8N0391"]}],"id":[{"id":"10.13039\/501100011892","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Objective: Ongoing debates focus on the role of human leukocyte antigen (HLA) class II expression in shaping clinical phenotypes of chronic inflammatory airway diseases. This study seeks to clarify the impact of class II HLA on chronic obstructive pulmonary disease (COPD) and asthma\u2013COPD overlap (ACO). Method: The expression levels of HLA-DQ\/DR in blood immune cells were analyzed in 116 participants: 41 with COPD, 37 with ACO, 20 with pure asthma, and 18 healthy subjects (HS). Results: In the COPD group, HLA-DR protein expression levels were significantly elevated on blood M2a monocytes (7695 \u00b1 3743 vs. 5391 \u00b1 3153 MFI, p = 0.026), helper T cells (2551 \u00b1 956 vs. 1836 \u00b1 531 MFI, adjusted p = 0.018), cytotoxic T cells (1591 \u00b1 531 vs. 1360 \u00b1 477 MFI, adjusted p = 0.036), and B cells (20,667 \u00b1 7985 vs. 15,694 \u00b1 2003 MFI, adjusted p = 0.031) compared to the HS group. Conversely, no significant changes were observed in the asthma group. In ACO patients, helper T cells showed increased HLA-DR protein expression (2416 \u00b1 914 MFI; adjusted p = 0.016) compared with the HS group. Higher levels of HLA-DR expression correlated with reduced pulmonary function, frequent exacerbations, and more severe symptoms. Following one year of treatment in 14 COPD and 16 ACO patients, HLA-DR protein expression on blood helper T cells, cytotoxic T cells, M2a monocytes, and neutrophils significantly declined (all p &lt; 0.05). In vitro experiments demonstrated that exposure of M2- or M1-polarized THP-1 cells to a stimulus mix containing cigarette smoke extract, house dust mite antigens, and lipopolysaccharide led to up-regulation of HLA-DR expression. This response was linked to increased apoptosis and reduced production of reactive oxygen species. Conclusions: Up-regulation of HLA-DR in COPD and ACO patients may represent a novel biomarker for assessing disease severity and treatment response. Additionally, it could serve as a useful tool to distinguish COPD and ACO from asthma.<\/jats:p>","DOI":"10.3390\/antiox14121507","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T08:46:52Z","timestamp":1765874812000},"page":"1507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Increased HLA-DR Expression on M2a Monocytes and Helper T Cells in Patients with COPD and Asthma\u2013COPD Overlap Contributes to Disease Severity via Apoptosis and ROS"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8695-5227","authenticated-orcid":false,"given":"Yung-Che","family":"Chen","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Graduate Institute of Clinical Medical Sciences, Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"},{"name":"Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Tung","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiu-Ping","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Yuan","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Division of Pulmonary and Critical Care Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801735, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-5954","authenticated-orcid":false,"given":"Yu-Ping","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Chien","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-9281","authenticated-orcid":false,"given":"Sum-Yee","family":"Leung","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Department of Respiratory Therapy, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7275-4675","authenticated-orcid":false,"given":"Chang-Chun","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Graduate Institute of Clinical Medical Sciences, Department of Medicine, College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Chih","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care Medicine, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan"},{"name":"Division of Pulmonary and Critical Care Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 801735, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"190185","DOI":"10.1183\/16000617.0185-2019","article-title":"Asthma-COPD overlap: Current understanding and the utility of experimental models","volume":"30","author":"Tu","year":"2021","journal-title":"Eur. 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