{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T10:10:05Z","timestamp":1764843005241,"version":"build-2065373602"},"reference-count":19,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T00:00:00Z","timestamp":1750204800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Elevated immunoglobulin G (IgG) levels are associated with worse lung function and disease severity in people with cystic fibrosis (PwCF). This study evaluated whether elevated IgG levels\u2014defined as values above the 97.5th percentile (Z-score \u2265 1.96 standard deviations above the mean)\u2014can predict progression to severe lung disease. Methods: A retrospective cohort study of children and adults with CF at a single-center clinic was performed. Patients with elevated baseline IgG Z-scores were compared to those with normal or low IgG levels. Progression to severe lung disease was defined as % predicted FEV1 &lt; 40%, referral for lung transplantation, or death. Kaplan\u2013Meier survival curves and Cox models were used to analyze clinical outcomes. A sensitivity analysis was conducted for patients aged 18 years or older. Results: Of 97 patients, 31 (31.9%) had elevated IgG levels. Progression to severe lung disease occurred in 14 (14.4%) patients, 12 (85.7%) of whom had elevated IgG. These patients were significantly older and had a higher prevalence of Pseudomonas aeruginosa colonization. Among adults, those with elevated IgG had lower baseline % predicted FEV1 and greater annual lung function decline. Elevated IgG was independently associated with progression to severe lung disease (adjusted hazard ratio [aHR]: 9.8; 95% CI: 1.9\u201348.6), even after adjusting for Pseudomonas colonization and annual % predicted FEV1 decline. Conclusions: Elevated IgG was associated with progression to severe lung disease in PwCF and correlated with older age, Pseudomonas colonization, and\u2014in adults\u2014lower baseline lung function and faster decline. These findings highlight elevated serum IgG as a meaningful prognostic biomarker for identifying high-risk PwCF who may benefit from closer monitoring and earlier intervention.<\/jats:p>","DOI":"10.3390\/jcm14124331","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T04:08:06Z","timestamp":1750219686000},"page":"4331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Elevated Immunoglobulin G as a Predictor of Progression to Severe Lung Disease in Cystic Fibrosis: A Longitudinal Cohort Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Ori","family":"Goldberg","sequence":"first","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Pediatric Pulmonary Service, Kaplan Medical Centre, Rehovot and the Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 7661041, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siwar","family":"Shekh-Yusuf","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6308-0181","authenticated-orcid":false,"given":"Miri","family":"Dotan","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moshe","family":"Heching","sequence":"additional","affiliation":[{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Pulmonary Institute, Rabin Medical Center, Petah Tikva 4941492, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eyal","family":"Jacobi","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meir","family":"Mei-Zahav","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"Blau","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huda","family":"Mussaffi","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4165-0144","authenticated-orcid":false,"given":"Dario","family":"Prais","sequence":"additional","affiliation":[{"name":"Pulmonary Institute, Schneider Children\u2019s Medical Center of Israel, Petach Tikva 4920235, Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0045-9380(85)90011-8","article-title":"Cystic fibrosis. 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