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Published in: Journal of Clinical Immunology 3/2023

16-11-2022 | Immunodeficiency | Original Article

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

Authors: Katherine N. Weller, John C. McDonnell, Jeffrey M. Albert, Mendel E. Singer, Fred H. Hsieh

Published in: Journal of Clinical Immunology | Issue 3/2023

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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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Literature
1.
go back to reference Lynch NR, Hagel IA, Palenque ME, Di Prisco MC, Escudero JE, Alejandra Corao L, et al. Relationship between helminthic infection and IgE response in atopic and nonatopic children in a tropical environment. J Allergy Clin Immunol. 1998;101:217–21.CrossRefPubMed Lynch NR, Hagel IA, Palenque ME, Di Prisco MC, Escudero JE, Alejandra Corao L, et al. Relationship between helminthic infection and IgE response in atopic and nonatopic children in a tropical environment. J Allergy Clin Immunol. 1998;101:217–21.CrossRefPubMed
2.
go back to reference Smith JK, Krishnaswamy GH, Dykes R, Reynolds S, Berk SL. Clinical manifestations of IgE hypogammaglobulinemia. Ann Allergy Asthma Immunol. Am College Allergy, Asthma Immunol. 1997;78:313–8.CrossRef Smith JK, Krishnaswamy GH, Dykes R, Reynolds S, Berk SL. Clinical manifestations of IgE hypogammaglobulinemia. Ann Allergy Asthma Immunol. Am College Allergy, Asthma Immunol. 1997;78:313–8.CrossRef
3.
go back to reference Ammann AJ, Cain WA, Ishizaka K, Hong R, Good RA. Immunoglobulin E deficiency in ataxia-telangiectasia. N Engl J Med. 1969;281:469–72.CrossRefPubMed Ammann AJ, Cain WA, Ishizaka K, Hong R, Good RA. Immunoglobulin E deficiency in ataxia-telangiectasia. N Engl J Med. 1969;281:469–72.CrossRefPubMed
4.
go back to reference Schoettler J, Schleissner LA. Familial lgE deficiency associated sinopulmonary disease * with chest. The American College of Chest Physicians. 1989;96:516–21. Schoettler J, Schleissner LA. Familial lgE deficiency associated sinopulmonary disease * with chest. The American College of Chest Physicians. 1989;96:516–21.
5.
go back to reference Levy DA, Chen J. Healthy IgE-deficient person. N Engl J Med. 1970; Levy DA, Chen J. Healthy IgE-deficient person. N Engl J Med. 1970;
6.
go back to reference Levin TA, Ownby DR, Smith PH, Peterson EL, Williams LK, Ford J, et al. Relationship between extremely low total serum IgE levels and rhinosinusitis. Ann Allergy, Asthma Immunol Am College Allergy, Asthma Immunol. 2006;97:650–2.CrossRef Levin TA, Ownby DR, Smith PH, Peterson EL, Williams LK, Ford J, et al. Relationship between extremely low total serum IgE levels and rhinosinusitis. Ann Allergy, Asthma Immunol Am College Allergy, Asthma Immunol. 2006;97:650–2.CrossRef
7.
go back to reference Jensen-Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M, et al. AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy Eur. J. Allergy Clin. Immunol. 2008. p. 1255–66. Jensen-Jarolim E, Achatz G, Turner MC, Karagiannis S, Legrand F, Capron M, et al. AllergoOncology: the role of IgE-mediated allergy in cancer. Allergy Eur. J. Allergy Clin. Immunol. 2008. p. 1255–66.
8.
go back to reference Josephs DH, Corrigan CJ, Gould HJ, Karagiannis SN. Epidemiological associations of allergy, IgE and cancer. Clin Exp Allergy. 2013;43. Josephs DH, Corrigan CJ, Gould HJ, Karagiannis SN. Epidemiological associations of allergy, IgE and cancer. Clin Exp Allergy. 2013;43.
9.
go back to reference Cui Y, Hill AW. Atopy and specific cancer sites: a review of epidemiological studies. Clin Rev Allergy Immunol. 2016;51:338–52.CrossRefPubMed Cui Y, Hill AW. Atopy and specific cancer sites: a review of epidemiological studies. Clin Rev Allergy Immunol. 2016;51:338–52.CrossRefPubMed
10.
go back to reference Helby J, Bojesen SE, Nielsen SF, Nordestgaard BG. IgE and risk of cancer in 37 747 individuals from the general population. Ann Oncol Elsevier Masson SAS. 2015;26:1784–90.CrossRef Helby J, Bojesen SE, Nielsen SF, Nordestgaard BG. IgE and risk of cancer in 37 747 individuals from the general population. Ann Oncol Elsevier Masson SAS. 2015;26:1784–90.CrossRef
11.
go back to reference Wulaningsih W, Holmberg L, Garmo H, Karagiannis SN, Ahlstedt S, Malmstrom H, et al. Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival. Oncoimmunology. 2016;5. Wulaningsih W, Holmberg L, Garmo H, Karagiannis SN, Ahlstedt S, Malmstrom H, et al. Investigating the association between allergen-specific immunoglobulin E, cancer risk and survival. Oncoimmunology. 2016;5.
12.
go back to reference Crawford G, Hayes MD, Seoane RC, Ward S, Dalessandri T, Lai C, et al. Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response. Nat Immunol. Springer US; 2018;19:859–70. Crawford G, Hayes MD, Seoane RC, Ward S, Dalessandri T, Lai C, et al. Epithelial damage and tissue γδ T cells promote a unique tumor-protective IgE response. Nat Immunol. Springer US; 2018;19:859–70.
13.
go back to reference Nigro EA, Brini AT, Yenagi VA, Ferreira LM, Achatz-Straussberger G, Ambrosi A, et al. Cutting edge: IgE plays an active role in tumor immunosurveillance in mice. J Immunol. 2016;197:2583–8.CrossRefPubMed Nigro EA, Brini AT, Yenagi VA, Ferreira LM, Achatz-Straussberger G, Ambrosi A, et al. Cutting edge: IgE plays an active role in tumor immunosurveillance in mice. J Immunol. 2016;197:2583–8.CrossRefPubMed
14.
go back to reference Platzer B, Elpek KG, Cremasco V, Baker K, Stout MM, Schultz C, et al. IgE/FcεRI-mediated antigen cross-presentation by dendritic cells enhances anti-tumor immune responses. Cell Rep. 2015;10:1487–95.CrossRefPubMedPubMedCentral Platzer B, Elpek KG, Cremasco V, Baker K, Stout MM, Schultz C, et al. IgE/FcεRI-mediated antigen cross-presentation by dendritic cells enhances anti-tumor immune responses. Cell Rep. 2015;10:1487–95.CrossRefPubMedPubMedCentral
15.
go back to reference Magen E, Schlesinger M, David M, Ben-Zion I, Vardy D. Selective IgE deficiency, immune dysregulation, and autoimmunity. Allergy Asthma Proc United States. 2014;35:e27–33. Magen E, Schlesinger M, David M, Ben-Zion I, Vardy D. Selective IgE deficiency, immune dysregulation, and autoimmunity. Allergy Asthma Proc United States. 2014;35:e27–33.
16.
go back to reference Ferastraoaru D, Gross R, Rosenstreich D. Increased malignancy incidence in IgE deficient patients not due to concomitant common variable immunodeficiency. Ann Allergy, Asthma Immunol. 2017;119:267–73.CrossRefPubMed Ferastraoaru D, Gross R, Rosenstreich D. Increased malignancy incidence in IgE deficient patients not due to concomitant common variable immunodeficiency. Ann Allergy, Asthma Immunol. 2017;119:267–73.CrossRefPubMed
17.
go back to reference Ferastraoaru D, Rosenstreich D. IgE deficiency and prior diagnosis of malignancy: results of the 2005–2006 National Health and Nutrition Examination Survey. Ann Allergy, Asthma Immunol. 2018;121:613–8.CrossRefPubMed Ferastraoaru D, Rosenstreich D. IgE deficiency and prior diagnosis of malignancy: results of the 2005–2006 National Health and Nutrition Examination Survey. Ann Allergy, Asthma Immunol. 2018;121:613–8.CrossRefPubMed
18.
go back to reference Ferastraoaru D, Rosenstreich D. IgE deficiency is associated with high rates of new malignancies: results of a longitudinal cohort study. J Allergy Clin Immunol Pract Am Academy Allergy, Asthma Immunol. 2020;8:413–5. Ferastraoaru D, Rosenstreich D. IgE deficiency is associated with high rates of new malignancies: results of a longitudinal cohort study. J Allergy Clin Immunol Pract Am Academy Allergy, Asthma Immunol. 2020;8:413–5.
19.
go back to reference Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.CrossRefPubMed Zou G. A modified Poisson regression approach to prospective studies with binary data. Am J Epidemiol. 2004;159:702–6.CrossRefPubMed
20.
go back to reference Ferastraoaru D, Jordakieva G, Jensen-Jarolim E. The other side of the coin: IgE deficiency, a susceptibility factor for malignancy occurrence. World Allergy Organ J. 2021;14:100505 (Elsevier Inc).CrossRefPubMedPubMedCentral Ferastraoaru D, Jordakieva G, Jensen-Jarolim E. The other side of the coin: IgE deficiency, a susceptibility factor for malignancy occurrence. World Allergy Organ J. 2021;14:100505 (Elsevier Inc).CrossRefPubMedPubMedCentral
21.
go back to reference Jensen-Jarolim E, Bax HJ, Bianchini R, Capron M, Corrigan C, Castells M, et al. AllergoOncology – the impact of allergy in oncology: EAACI position paper. Allergy Eur J Allergy Clin Immunol. 2017;72:866–87.CrossRef Jensen-Jarolim E, Bax HJ, Bianchini R, Capron M, Corrigan C, Castells M, et al. AllergoOncology – the impact of allergy in oncology: EAACI position paper. Allergy Eur J Allergy Clin Immunol. 2017;72:866–87.CrossRef
22.
go back to reference Karagiannis P, Singer J, Hunt J, Gan SKE, Rudman SM, Mechtcheriakova D, et al. Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. Cancer Immunol Immunother. 2009;58:915–30.CrossRefPubMed Karagiannis P, Singer J, Hunt J, Gan SKE, Rudman SM, Mechtcheriakova D, et al. Characterisation of an engineered trastuzumab IgE antibody and effector cell mechanisms targeting HER2/neu-positive tumour cells. Cancer Immunol Immunother. 2009;58:915–30.CrossRefPubMed
23.
go back to reference Spillner E, Plum M, Blank S, Miehe M, Singer J, Braren I. Recombinant IgE antibody engineering to target EGFR. Cancer Immunol Immunother. 2012. p. 1565–73. Spillner E, Plum M, Blank S, Miehe M, Singer J, Braren I. Recombinant IgE antibody engineering to target EGFR. Cancer Immunol Immunother. 2012. p. 1565–73.
24.
go back to reference Pellizzari G, Hoskin C, Crescioli S, Mele S, Gotovina J, Chiaruttini G, et al. IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states. EBioMedicine The Authors. 2019;43:67–81.CrossRef Pellizzari G, Hoskin C, Crescioli S, Mele S, Gotovina J, Chiaruttini G, et al. IgE re-programs alternatively-activated human macrophages towards pro-inflammatory anti-tumoural states. EBioMedicine The Authors. 2019;43:67–81.CrossRef
26.
go back to reference Adcock IM. Cancers related to immunodeficiencies : Update and Perspectives. 2016;7:1–13 Adcock IM. Cancers related to immunodeficiencies : Update and Perspectives. 2016;7:1–13
Metadata
Title
Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study
Authors
Katherine N. Weller
John C. McDonnell
Jeffrey M. Albert
Mendel E. Singer
Fred H. Hsieh
Publication date
16-11-2022
Publisher
Springer US
Published in
Journal of Clinical Immunology / Issue 3/2023
Print ISSN: 0271-9142
Electronic ISSN: 1573-2592
DOI
https://doi.org/10.1007/s10875-022-01401-7

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