{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:58:45Z","timestamp":1781636325152,"version":"3.54.5"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T00:00:00Z","timestamp":1771977600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":34,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>COPD is a disease of progressive and irreversible airflow obstruction, with exacerbations (AECOPD) often triggered by infection. Immunoglobulins play an important role in immune defense and immune regulation, however their role in COPD is poorly understood. Therefore, the purpose of our systematic review and meta-analysis was to assess serum, sputum, and bronchoalveolar lavage (BAL) levels of IgG, IgG subclasses, IgA, and IgM in COPD, and the association between immunoglobulins and key clinical outcomes.<\/jats:p>\n                  <jats:p>EMBASE and Ovid MEDLINE were searched from inception to April 2024. Study screening and extraction were completed by two independent reviewers. Non-randomized studies assessing immunoglobulin levels were included. Data was analyzed using RevMan 5.<\/jats:p>\n                  <jats:p>\n                    Our search identified 1897 studies; 36 were included in meta-analysis. Compared with healthy controls, individuals with COPD showed elevated secretory IgA levels (Standard Mean Difference (SMD) 1.68 [95% Confidence Interval (CI), 0.78, 2.59],\n                    <jats:italic>N<\/jats:italic>\n                    \u2009=\u20092). IgG2 was significantly lower in COPD compared to controls [SMD\u2009\u2212\u20090.91 (-1.24, -0.58)]. There was no significant SMD in other IgG subclasses, serum IgG, IgM, or BAL IgA. Serum IgG and subclass levels did not differ between stable and AECOPD (SMD 0.10 [-0.61, 0.81]).\n                  <\/jats:p>\n                  <jats:p>Compared to COPD with normal IgG, the COPD-low IgG group had increased risk of COPD admissions (OR 1.32 [95% CI, 1.11, 1.56]), lower FEV1\/FVC % (SMD\u2009\u2212\u20092.26[-3.3, -1.14] and FVC (SMD \u2212\u20090.31[-0.58, -0.05]). Systemic steroid use trended higher in COPD-low IgG (OR 2.32[0.94, 5.72]). There was no difference in 1-year mortality.<\/jats:p>\n                  <jats:p>In conclusion, serum IgG2 was lower in COPD and low IgG was associated with increased COPD-related admissions. These findings support further investigation of IgG as a potential biomarker and therapeutic target in COPD.<\/jats:p>","DOI":"10.1186\/s12931-026-03590-w","type":"journal-article","created":{"date-parts":[[2026,2,25]],"date-time":"2026-02-25T06:38:28Z","timestamp":1772001508000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Levels of immunoglobulin isotypes in serum and respiratory samples of patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis"],"prefix":"10.1186","volume":"27","author":[{"given":"Dana","family":"Unninayar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oluwafemi","family":"Segun-Ige","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luana Leticia Teixeira Nunes","family":"Porto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley","family":"Shea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald William","family":"Cameron","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juthaporn","family":"Cowan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,25]]},"reference":[{"key":"3590_CR1","unstructured":"2024 GOLD Report - Global Initiative for Chronic Obstructive Lung Disease - GOLD. https:\/\/goldcopd.org\/2024-gold-report\/. Accessed July 6. 2025."},{"issue":"JUN","key":"3590_CR2","doi-asserted-by":"publisher","first-page":"1041","DOI":"10.3389\/FMICB.2017.01041","volume":"8","author":"DE Morris","year":"2017","unstructured":"Morris DE, Cleary DW, Clarke SC. Secondary Bacterial Infections Associated with Influenza Pandemics. Front Microbiol. 2017;8(JUN):1041. https:\/\/doi.org\/10.3389\/FMICB.2017.01041.","journal-title":"Front Microbiol"},{"key":"3590_CR3","unstructured":"Cochrane Handbook for Systematic Reviews of Interventions | Cochrane. https:\/\/www.cochrane.org\/authors\/handbooks-and-manuals\/handbook. Accessed July 6. 2025."},{"key":"3590_CR4","unstructured":"PROSPERO. https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD42020192220. Accessed July 6, 2025."},{"key":"3590_CR5","unstructured":"Covidence - Better systematic review management. https:\/\/www.covidence.org\/#. Accessed July 6. 2025."},{"key":"3590_CR6","unstructured":"Risk of bias tools - ROBINS-I tool. https:\/\/www.riskofbias.info\/welcome\/home. Accessed July 6. 2025."},{"key":"3590_CR7","doi-asserted-by":"publisher","unstructured":"Hai CN, Ba TT, Duc TB, Xuan CH, Manh TV. Serum immunoglobulin levels in group E of chronic obstructive pulmonary disease: insights for clinical management and immunoglobulin therapy strategies. BMC Pulm Med. 2024;24(1). https:\/\/doi.org\/10.1186\/S12890-024-03185-5.","DOI":"10.1186\/S12890-024-03185-5"},{"key":"3590_CR8","doi-asserted-by":"publisher","unstructured":"Palikhe NS, Niven M, Fuhr D et al. Low immunoglobulin levels affect the course of COPD in hospitalized patients. Published online 2023. https:\/\/doi.org\/10.1186\/s13223-023-00762-x.","DOI":"10.1186\/s13223-023-00762-x"},{"key":"3590_CR9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0194924","author":"N Putcha","year":"2018","unstructured":"Putcha N, Paul GG, Azar A, et al. Lower serum IgA is associated with COPD exacerbation risk in SPIROMICS. Published online. 2018. https:\/\/doi.org\/10.1371\/journal.pone.0194924.","journal-title":"Published online"},{"key":"3590_CR10","unstructured":"Janeway\u2019s Immunobiology |, Kenneth M, Murphy C, Weaver, Leslie J. Berg | W. W. Norton & Company. https:\/\/wwnorton.com\/books\/9780393884890. Accessed July 6, 2025."},{"issue":"5","key":"3590_CR11","doi-asserted-by":"publisher","first-page":"592","DOI":"10.1164\/rccm.201802-0352OC","volume":"199","author":"MZ Ladjemi","year":"2019","unstructured":"Ladjemi MZ, Martin C, Lecocq M, et al. Increased IgA Expression in Lung Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease. Am J Respir Crit Care Med. 2019;199(5):592\u2013602. https:\/\/doi.org\/10.1164\/rccm.201802-0352OC.","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"3590_CR12","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1164\/RCCM.201311-1971OC","volume":"190","author":"ST Gohy","year":"2014","unstructured":"Gohy ST, Detry BR, Lecocq M, et al. Polymeric immunoglobulin receptor down-regulation in chronic obstructive pulmonary disease: Persistence in the cultured epithelium and role of transforming growth factor-\u03b2. Am J Respir Crit Care Med. 2014;190(5):509\u201321. https:\/\/doi.org\/10.1164\/RCCM.201311-1971OC.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"3590_CR13","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/J.ARCMED.2017.01.007","volume":"48","author":"Y Xiong","year":"2017","unstructured":"Xiong Y, Gao S, Luo G, et al. Increased Circulating Autoantibodies Levels of IgG, IgA, IgM Against Cytokeratin 18 and Cytokeratin 19 in Chronic Obstructive Pulmonary Disease. Arch Med Res. 2017;48(1):79\u201387. https:\/\/doi.org\/10.1016\/J.ARCMED.2017.01.007.","journal-title":"Arch Med Res"},{"issue":"4","key":"3590_CR14","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1016\/j.chest.2020.04.058","volume":"158","author":"FS Leitao Filho","year":"2020","unstructured":"Leitao Filho FS, Mattman A, Schellenberg R, et al. Serum IgG Levels and Risk of COPD Hospitalization: A Pooled Meta-analysis. Chest. 2020;158(4):1420\u201330. https:\/\/doi.org\/10.1016\/j.chest.2020.04.058.","journal-title":"Chest"},{"issue":"6","key":"3590_CR15","doi-asserted-by":"publisher","first-page":"500","DOI":"10.3390\/ARM90060056","volume":"90","author":"T Ba Ta","year":"2022","unstructured":"Ba Ta T, Tran Viet T, Xuan Nguyen K, et al. Changes in Serum Immunoglobulin G Subclasses during the Treatment of Patients with Chronic Obstructive Pulmonary Disease with Infectious Exacerbations. Adv Respir Med. 2022;90(6):500\u201310. https:\/\/doi.org\/10.3390\/ARM90060056.","journal-title":"Adv Respir Med"},{"key":"3590_CR16","unstructured":"Karnak D, Beder S, Kayacan O, Karaca L. IgG subclass levels in ELF in COPD. 2001; 31: 235\u201341."},{"issue":"11","key":"3590_CR17","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1016\/J.JAIP.2021.09.031","volume":"9","author":"AA Petrov","year":"2021","unstructured":"Petrov AA, Adatia A, Jolles S, Nair P, Azar A, Walter JE, Antibody Deficiency. Chronic Lung Disease, and Comorbid Conditions: A Case-Based Approach. J Allergy Clin Immunology: Pract. 2021;9(11):3899\u2013908. https:\/\/doi.org\/10.1016\/J.JAIP.2021.09.031.","journal-title":"J Allergy Clin Immunology: Pract"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12931-026-03590-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03590-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-026-03590-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:50:28Z","timestamp":1781635828000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12931-026-03590-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,25]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["3590"],"URL":"https:\/\/doi.org\/10.1186\/s12931-026-03590-w","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,25]]},"assertion":[{"value":"2 November 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Dr Cowan received honoraria from Takeda, Pfizer, AstraZeneca for consultancy work unrelated to the work presented in this manuscript. Dr Cowan holds a Research Chair Award from the Faculty of Medicine, University of Ottawa. Dr. Cameron received honoraria from CSL Behring and Takeda for consultancy work not related to the manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"151"}}