{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T14:09:07Z","timestamp":1780409347291,"version":"3.54.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T00:00:00Z","timestamp":1611273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002347","name":"Bundesministerium f\u00fcr Bildung und Forschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002347","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>In Cystic Fibrosis (CF), the airways are often colonized by opportunistic fungi. The most frequently detected mold is <jats:italic>Aspergillus fumigatus<\/jats:italic> (<jats:italic>Af<\/jats:italic>). <jats:italic>Af<\/jats:italic> diseases are associated with significant morbidity and mortality. The most common clinical picture caused by <jats:italic>Af<\/jats:italic> is allergic bronchopulmonary aspergillosis (ABPA), triggered by an immunological reaction against <jats:italic>Af<\/jats:italic>. <jats:italic>Af<\/jats:italic> bronchitis and invasive aspergillosis rarely occur in CF as a result of spore colonization and germination. Since pulmonary mycoses and exacerbations by other pathogens overlap in clinical, radiological, and immunological characteristics, diagnosis still remains a challenge. The search for reliable, widely available biomarkers for <jats:italic>Af<\/jats:italic> diseases is therefore still an important task today.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p><jats:italic>Af-<\/jats:italic>specific IgG m3 is broadly available. Sensitivity and specificity data are contradictory and differ depending on the study population. In our prospective study on pulmonary <jats:italic>Af<\/jats:italic> diseases in CF, we determined specific IgG m3 in order to test its suitability as a biomarker for acute <jats:italic>Af<\/jats:italic> diseases and as a follow-up parameter.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this prospective single center study, 109 patients with CF were screened from 2016 to 2019 for <jats:italic>Af<\/jats:italic>-associated diseases. According to diagnostic criteria, they were divided into four groups (control, bronchitis, ABPA, pneumonia). The groups were compared with respect to the level of <jats:italic>Af<\/jats:italic>-specific IgG (ImmunoCAP Gm3). We performed a receiver operating characteristic (ROC) curve analysis to determine cut-off, sensitivity and specificity. Twenty-one patients could be enrolled for a follow-up examination.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Of the 109 patients, 36 were classified as acute <jats:italic>Af<\/jats:italic>-disease (<jats:italic>Af<\/jats:italic> bronchitis, ABPA, <jats:italic>Af<\/jats:italic> pneumonia). Of these, 21 patients completed follow up-screening. The median <jats:italic>Af<\/jats:italic>-specific Gm3 was higher in the acute <jats:italic>Af<\/jats:italic>-disease groups. There was a significant difference in <jats:italic>Af<\/jats:italic>-specific IgG m3 compared to the control group without acute <jats:italic>Af<\/jats:italic>-disease. Overall, there was a large interindividual distribution of Gm3. A cut-off value of 78.05 mg\/L for Gm3 was calculated to discriminate controls and patients with ABPA\/pneumonia with a specificity of 75% and a sensitivity of 74.6%. The follow up examination of 21 patients showed a decrease of Gm3 in most patients without statistical significance due to the small number of follow up patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>Af\u00a0<\/jats:italic>specific IgG may be a useful biomarker for acute ABPA and\u00a0<jats:italic>Af\u00a0<\/jats:italic>pneumonia, but not for\u00a0<jats:italic>Af<\/jats:italic>\u00a0bronchitis in CF. However, due to the large interindividual variability of Gm3, it should only be interpreted alongside other biomarkers. Therefore, due to its broad availability, it could be suitable as a biomarker for ABPA and <jats:italic>Af<\/jats:italic> pneumonia in CF, if the results can be supported by a larger multicenter cohort.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2020.602836","type":"journal-article","created":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T04:34:34Z","timestamp":1611290074000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":13,"title":["Prospective Evaluation of Aspergillus fumigatus-Specific IgG in Patients With Cystic Fibrosis"],"prefix":"10.3389","volume":"10","author":[{"given":"Patience","family":"Eschenhagen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Grehn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Schwarz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1111\/myc.12541","article-title":"Role of Aspergillus fumigatus-specific IgG in diagnosis and monitoring treatment response in allergic bronchopulmonary aspergillosis","volume":"60","author":"Agarwal","year":"2017","journal-title":"Mycoses"},{"key":"B2","doi-asserted-by":"publisher","first-page":"924","DOI":"10.1099\/jmm.0.000991","article-title":"Serum IgE\u00a0and IgG reactivity to Aspergillus recombinant antigens in patients with\u00a0cystic fibrosis","volume":"68","author":"Alghamdi","year":"2019","journal-title":"J. Med. Microbiol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1378\/chest.09-1103","article-title":"The effect of chronic infection with Aspergillus fumigatus on lung function and hospitalization in patients with cystic fibrosis","volume":"137","author":"Amin","year":"2010","journal-title":"Chest"},{"key":"B4","doi-asserted-by":"publisher","first-page":"560","DOI":"10.1016\/j.jaci.2013.04.007","article-title":"Novel immunologic classification of aspergillosis in adult cystic fibrosis","volume":"132","author":"Baxter","year":"2013","journal-title":"J. Allergy Clin. Immunol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E197","DOI":"10.1111\/1469-0691.12133","article-title":"Performance of two Aspergillus IgG EIA assays compared with the precipitin test in chronic and allergic aspergillosis","volume":"19","author":"Baxter","year":"2013","journal-title":"Clin. Microbiol Infect."},{"key":"B6","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/S2213-2600(19)30337-6","article-title":"The future of cystic fibrosis care: a global perspective","volume":"8","author":"Bell","year":"2020","journal-title":"Lancet Respiratory Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1007\/s11046-017-0190-0","article-title":"Aspergillus Bronchitis in Patients with Cystic Fibrosis","volume":"183","author":"Brandt","year":"2018","journal-title":"Mycopathologia"},{"key":"B8","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1111\/j.1749-6632.2012.06816.x","article-title":"Aspergillus bronchitis without significant immunocompromise","volume":"1272","author":"Chrdle","year":"2012","journal-title":"Ann. N Y Acad. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1038\/nm.2715","article-title":"Cystic fibrosis: a mucosal immunodeficiency syndrome","volume":"18","author":"Cohen","year":"2012","journal-title":"Nat. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"S77","DOI":"10.3109\/13693786.2010.514301","article-title":"Serum markers for allergic bronchopulmonary aspergillosis in cystic fibrosis: State of the art and further challenges","author":"Delhaes","year":"2010","journal-title":"Med. Mycol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.150.6.7952609","article-title":"Development of Immune Responses to Aspergillus at an Early Age in Children with Cystic Fibrosis","volume":"150","author":"el-Dahr","year":"1994","journal-title":"Am. J. Respir. Crlt Care Med."},{"key":"B12","doi-asserted-by":"publisher","first-page":"632","DOI":"10.1097\/MCP.0000000000000106","article-title":"Aspergillus and cystic fibrosis: old disease - new classifications","volume":"20","author":"Felton","year":"2014","journal-title":"Curr. Opin. Pulm Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1330","DOI":"10.1128\/CVI.00200-10","article-title":"Recombinant allergens combined with biological markers in the diagnosis of allergic bronchopulmonary aspergillosis in cystic fibrosis patients","volume":"17","author":"Fricker-Hidalgo","year":"2010","journal-title":"Clin. Vaccine Immunol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.alit.2015.08.004","article-title":"Serological diagnosis of allergic bronchopulmonary mycosis: Progress and challenges","volume":"65","author":"Fukutomi","year":"2016","journal-title":"Allergol Int."},{"key":"B15","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1586\/14737159.9.2.157","article-title":"Allergic bronchopulmonary aspergillosis: the hunt for a diagnostic serological marker in cystic fibrosis patients","volume":"9","author":"Hafen GM","year":"2009","journal-title":"Expert Rev. Mol. Diagn"},{"key":"B16","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1016\/j.jcf.2018.01.008","article-title":"Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis","volume":"17","author":"Hong","year":"2018","journal-title":"J. Cystic Fibrosis Off. J. Eur. Cystic Fibrosis Soc."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1787","DOI":"10.1002\/ppul.24465","article-title":"An investigation into biomarkers for the diagnosis of ABPA and aspergillus disease in cystic fibrosis","volume":"54","author":"Keown","year":"2019","journal-title":"Pediatr. Pulmonol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1136\/thoraxjnl-2014-206291","article-title":"The clinical spectrum of pulmonary aspergillosis","volume":"70","author":"Kosmidis","year":"2015","journal-title":"Thorax"},{"key":"B19","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1183\/09059180.00001011","article-title":"Pulmonary aspergillosis: a clinical review","volume":"20","author":"Kousha","year":"2011","journal-title":"Eur. Respir. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"S189","DOI":"10.1080\/13693780500064763","article-title":"Aspergillus antigens: which are important","author":"Kurup","year":"2005","journal-title":"Med. Mycol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1183\/09031936.00078107","article-title":"Comparison of serum markers for allergic bronchopulmonary aspergillosis in cystic fibrosis","volume":"31","author":"Latzin","year":"2008","journal-title":"Eur. Respiratory J."},{"key":"B22","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1097\/MCP.0b013e328365ab74","article-title":"Fungal infections and treatment in cystic fibrosis","volume":"19","author":"Middleton","year":"2013","journal-title":"Curr. Opin. Pulm Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1097\/MCP.0b013e32833e24a6","article-title":"Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis","volume":"16","author":"Moss","year":"2010","journal-title":"Curr. Opin. Pulmonary Med."},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1164\/ajrccm.152.2.7633719","article-title":"Identification of allergic bronchopulmonary aspergillosis in cystic fibrosis patients by recombinant Aspergillus fumigatus I_a-specific serology","volume":"152","author":"Nikolaizik","year":"1995","journal-title":"Am. J. Respir. Crlt Care Med."},{"key":"B25","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1080\/13693780802609604","article-title":"Occurrence and relevance of filamentous fungi in respiratory secretions of patients with cystic fibrosis\u2013a review","volume":"47","author":"Pihet","year":"2009","journal-title":"Med. Mycol"},{"key":"B26","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s40629-019-0099-x","article-title":"Update of reference values for IgG antibodies against typical antigens of hypersensitivity pneumonitis","volume":"28","author":"Raulf","year":"2019","journal-title":"Allergo J. Int."},{"key":"B27","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1007\/s11046-017-0229-2","article-title":"Fungus-Specific CD4 T Cells as Specific Sensors for Identification of Pulmonary Fungal Infections","volume":"183","author":"Scheffold","year":"2018","journal-title":"Mycopathologia"},{"key":"B28","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1007\/s11046-017-0205-x","article-title":"Organization of Patient Management and Fungal Epidemiology in Cystic Fibrosis","volume":"183","author":"Schwarz","year":"2018","journal-title":"Mycopathologia"},{"key":"B29","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1007\/s11046-017-0199-4","article-title":"Invasive Pulmonary Fungal Infections in Cystic Fibrosis","volume":"183","author":"Schwarz","year":"2018","journal-title":"Mycopathologia"},{"key":"B30","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1111\/myc.12815","article-title":"Diagnostic cut-off of Aspergillus fumigatus-specific IgG in the diagnosis of chronic pulmonary aspergillosis","volume":"61","author":"Sehgal","year":"2018","journal-title":"Mycoses"},{"key":"B31","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1111\/myc.12987","article-title":"Efficiency of A fumigatus-specific IgG and galactomannan testing in the diagnosis of simple aspergilloma","volume":"62","author":"Sehgal","year":"2019","journal-title":"Mycoses"},{"key":"B32","doi-asserted-by":"publisher","first-page":"222","DOI":"10.1378\/chest.130.1.222","article-title":"Aspergillus Bronchitis in Cystic Fibrosis","volume":"130","author":"Shoseyov","year":"2006","journal-title":"Chest"},{"key":"B33","doi-asserted-by":"publisher","first-page":"670","DOI":"10.1183\/09031936.00119714","article-title":"A contemporary survival analysis of individuals with cystic fibrosis: a cohort study","volume":"45","author":"Stephenson","year":"2015","journal-title":"Eur. Respiratory J."},{"key":"B34","doi-asserted-by":"publisher","first-page":"S225","DOI":"10.1086\/376525","article-title":"Allergic Bronchopulmonary Aspergillosis in Cystic Fibrosis\u2014State of the Art: Cystic Fibrosis Foundation Consensus Conference","author":"Stevens","year":"2003","journal-title":"Clin. Infect. Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1785","DOI":"10.1373\/clinchem.2006.067546","article-title":"Quantification of IgG antibodies to Aspergillus fumigatus and pigeon antigens by ImmunoCAP technology: an alternative to the precipitation technique","volume":"52","author":"Van Hoeyveld","year":"2006","journal-title":"Clin. Chem."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.602836\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,22]],"date-time":"2021-01-22T04:34:36Z","timestamp":1611290076000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.602836\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,22]]},"references-count":35,"alternative-id":["10.3389\/fcimb.2020.602836"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2020.602836","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,22]]},"article-number":"602836"}}