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Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study

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Abstract

Purpose

The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects.

Methods

Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype.

Results

Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27–1.75) (hazard ratio 1.28, 95% CI 1.08–1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29–3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13–2.05).

Conclusion

Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular.

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Acknowledgements

The authors would like to acknowledge the efforts of Robert Burton, Business Intelligence at the Cleveland Clinic, for database analytics.

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Author notes

  1. Katherine N. Weller and John C. McDonnell contributed equally to this manuscript.

Authors and Affiliations

  1. Department of Allergy and Immunology, Respiratory Institute, Cleveland Clinic, 9500 Euclid Avenue/A90, Cleveland, OH, 44195, USA

    Katherine N. Weller, John C. McDonnell & Fred H. Hsieh

  2. Department of Population and Quantitative Health Sciences, Case Western Reserve School of Medicine, Cleveland, OH, USA

    John C. McDonnell, Jeffrey M. Albert & Mendel E. Singer

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  1. Katherine N. Weller
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Contributions

All authors have approved the final version to be published and are accountable for the work. Authors contributed to the following aspects of the manuscript as outlined:

KW: data acquisition, data analysis, and interpretation; contribution to the first draft and editing of the final draft

JM: data acquisition, statistical analyses, data analysis, and interpretation, contribution to the first draft and editing of the final draft

JA: data analysis, statistical analysis, interpretation of data, revisions for intellectual content

MS: data analysis, statistical analysis, interpretation of data, revisions for intellectual content

FH: IRB project approval, data acquisition, data analysis and interpretation, revisions of all drafts for intellectual content, editing of the final draft

Corresponding author

Correspondence to Fred H. Hsieh.

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This retrospective chart review was approved by the Cleveland Clinic Institutional Review Board (IRB).

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The authors declare no competing interests.

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Weller, K.N., McDonnell, J.C., Albert, J.M. et al. Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study. J Clin Immunol 43, 568–577 (2023). https://doi.org/10.1007/s10875-022-01401-7

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  • DOI: https://doi.org/10.1007/s10875-022-01401-7

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