Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults

Background: Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited. Objective: We aimed to analyze the diagnostic value of very high IgE in adults. Methods: A retrospective nationwide study was conducted using the ele...

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Main Authors: Shay Nemet, MD, Daniel Elbirt, MD, Ramon Cohen, MD, Keren Mahlab-Guri, MD, Shira Bezalel-Rosenberg, MD, Ilan Asher, MD, Aviv Talmon, MD, Limor Rubin, MD, Yaarit Ribak, MD, Ruslan Sergienko, MHA, Udi Nussinovitch, MD, PhD, Yuval Tal, MD, PhD, Oded Shamriz, MD
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Journal of Allergy and Clinical Immunology: Global
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772829325000049
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author Shay Nemet, MD
Daniel Elbirt, MD
Ramon Cohen, MD
Keren Mahlab-Guri, MD
Shira Bezalel-Rosenberg, MD
Ilan Asher, MD
Aviv Talmon, MD
Limor Rubin, MD
Yaarit Ribak, MD
Ruslan Sergienko, MHA
Udi Nussinovitch, MD, PhD
Yuval Tal, MD, PhD
Oded Shamriz, MD
author_facet Shay Nemet, MD
Daniel Elbirt, MD
Ramon Cohen, MD
Keren Mahlab-Guri, MD
Shira Bezalel-Rosenberg, MD
Ilan Asher, MD
Aviv Talmon, MD
Limor Rubin, MD
Yaarit Ribak, MD
Ruslan Sergienko, MHA
Udi Nussinovitch, MD, PhD
Yuval Tal, MD, PhD
Oded Shamriz, MD
author_sort Shay Nemet, MD
collection DOAJ
description Background: Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited. Objective: We aimed to analyze the diagnostic value of very high IgE in adults. Methods: A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (P < .05). Results: The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, P < .001), eosinophilic disorders (0.42% vs 0.06%, P < .001), and IEI (0.35% vs 0.20%, P = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; P = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; P = .059). Risk of eosinophilic disorders was increased across all age groups (P < .001). Conclusions: Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.
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spelling doaj-art-a5663e8183be45cab0f22cf4f281f3622025-08-20T03:49:03ZengElsevierJournal of Allergy and Clinical Immunology: Global2772-82932025-05-014210040310.1016/j.jacig.2025.100403Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adultsShay Nemet, MD0Daniel Elbirt, MD1Ramon Cohen, MD2Keren Mahlab-Guri, MD3Shira Bezalel-Rosenberg, MD4Ilan Asher, MD5Aviv Talmon, MD6Limor Rubin, MD7Yaarit Ribak, MD8Ruslan Sergienko, MHA9Udi Nussinovitch, MD, PhD10Yuval Tal, MD, PhD11Oded Shamriz, MD12Allergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Kaplan Medical Center, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelDepartment of Health Policy and Management, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, IsraelDepartment of Cardiology, Edith Wolfson Medical Center, Holon, Israel; Faculty of Medicine, Tel Aviv University, Tel Aviv, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, IsraelAllergy and Clinical Immunology Unit, Department of Medicine, Hadassah Medical Organization, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel; Corresponding author: Oded Shamriz, MD, Allergy and Clinical Immunology Unit, Hadassah Medical Organization, Jerusalem, Israel.Background: Very high serum IgE (≥1000 IU/mL) is reported in atopic disorders. However, data on its significance in nonallergic disorders are limited. Objective: We aimed to analyze the diagnostic value of very high IgE in adults. Methods: A retrospective nationwide study was conducted using the electronic database of Clalit Health Services, covering adults (≥18 years) treated between 2002 and 2022. Subjects with IgE ≥ 1000 IU/mL were compared to the controls with IgE < 100 IU/mL across 3 age groups (18-30, 31-64, and ≥65 years). Outcomes included eosinophilic, autoimmune, autoinflammatory, and cardiovascular disorders (CVD), cancer, and inborn errors of immunity (IEI). A multivariable Cox regression model determined statistical significance (P < .05). Results: The study included 118,211 subjects: 110,116 controls and 8635 with very high IgE levels. Excluding insect sting and drug allergies, very high IgE was more common across all tested allergic disorders, with asthma showing the highest rate (64.49%). Univariable analysis showed higher prevalence of CVD (3.88% vs 2.72%, P < .001), eosinophilic disorders (0.42% vs 0.06%, P < .001), and IEI (0.35% vs 0.20%, P = .004) in the very high IgE group. Multivariable analysis revealed age-dependent significant results: higher CVD risk in ages 31-64 (hazard ratio = 1.249; 95% confidence interval, 1.054-1.481; P = .010) and borderline IEI association in ages 18-30 (hazard ratio = 1.802; 95% confidence interval, 0.978-3.321; P = .059). Risk of eosinophilic disorders was increased across all age groups (P < .001). Conclusions: Very high IgE level of ≥1000 IU/mL is associated with increased risks of CVD, IEI, and eosinophilic disorders. Physicians should consider further assessment for these conditions in nonallergic patients with very high IgE levels.http://www.sciencedirect.com/science/article/pii/S2772829325000049IgEvery high IgEimmunoglobulin Epopulation-based study
spellingShingle Shay Nemet, MD
Daniel Elbirt, MD
Ramon Cohen, MD
Keren Mahlab-Guri, MD
Shira Bezalel-Rosenberg, MD
Ilan Asher, MD
Aviv Talmon, MD
Limor Rubin, MD
Yaarit Ribak, MD
Ruslan Sergienko, MHA
Udi Nussinovitch, MD, PhD
Yuval Tal, MD, PhD
Oded Shamriz, MD
Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
Journal of Allergy and Clinical Immunology: Global
IgE
very high IgE
immunoglobulin E
population-based study
title Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
title_full Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
title_fullStr Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
title_full_unstemmed Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
title_short Clinical significance of very high IgE levels (≥1000 IU/mL): Population-based study of 118,211 adults
title_sort clinical significance of very high ige levels ≥1000 iu ml population based study of 118 211 adults
topic IgE
very high IgE
immunoglobulin E
population-based study
url http://www.sciencedirect.com/science/article/pii/S2772829325000049
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