Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID)

Monica G. Lawrence*, Thamiris V. Palacios-Kibler, Lisa J. Workman, Alexander J. Schuyler, John W. Steinke, Spencer C. Payne, Emily C. McGowan, James Patrie, Ramsay L. Fuleihan, Kathleen E. Sullivan, Patricia L. Lugar, Camellia L. Hernandez, Douglas E. Beakes, James W. Verbsky, Thomas A.E. Platts-Mills, Charlotte Cunningham-Rundles, John M. Routes, Larry Borish

*Corresponding author for this work

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9–5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6–85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalJournal of Clinical Immunology
Volume38
Issue number3
DOIs
StatePublished - Apr 1 2018

Fingerprint

Common Variable Immunodeficiency
Immunoglobulin E
Serum
Agammaglobulinemia
Passive Immunization
Immunoglobulin G
Allergens

Keywords

  • Common variable immunodeficiency
  • IgE
  • IgE deficiency
  • secondary hypogammaglobulinemia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Lawrence, M. G., Palacios-Kibler, T. V., Workman, L. J., Schuyler, A. J., Steinke, J. W., Payne, S. C., ... Borish, L. (2018). Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). Journal of Clinical Immunology, 38(3), 225-233. https://doi.org/10.1007/s10875-018-0476-0
Lawrence, Monica G. ; Palacios-Kibler, Thamiris V. ; Workman, Lisa J. ; Schuyler, Alexander J. ; Steinke, John W. ; Payne, Spencer C. ; McGowan, Emily C. ; Patrie, James ; Fuleihan, Ramsay L. ; Sullivan, Kathleen E. ; Lugar, Patricia L. ; Hernandez, Camellia L. ; Beakes, Douglas E. ; Verbsky, James W. ; Platts-Mills, Thomas A.E. ; Cunningham-Rundles, Charlotte ; Routes, John M. ; Borish, Larry. / Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). In: Journal of Clinical Immunology. 2018 ; Vol. 38, No. 3. pp. 225-233.
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abstract = "Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3{\%} (95{\%} CI, 1.9–5.7{\%}) of the general population. In contrast, an undetectable IgE occurs in 75.6{\%} (95{\%} CI, 65.6–85.7{\%}) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3{\%} of patients). IgE is > 2 IU/ml in 91.2{\%} of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5{\%} of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.",
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Lawrence, MG, Palacios-Kibler, TV, Workman, LJ, Schuyler, AJ, Steinke, JW, Payne, SC, McGowan, EC, Patrie, J, Fuleihan, RL, Sullivan, KE, Lugar, PL, Hernandez, CL, Beakes, DE, Verbsky, JW, Platts-Mills, TAE, Cunningham-Rundles, C, Routes, JM & Borish, L 2018, 'Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID)', Journal of Clinical Immunology, vol. 38, no. 3, pp. 225-233. https://doi.org/10.1007/s10875-018-0476-0

Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). / Lawrence, Monica G.; Palacios-Kibler, Thamiris V.; Workman, Lisa J.; Schuyler, Alexander J.; Steinke, John W.; Payne, Spencer C.; McGowan, Emily C.; Patrie, James; Fuleihan, Ramsay L.; Sullivan, Kathleen E.; Lugar, Patricia L.; Hernandez, Camellia L.; Beakes, Douglas E.; Verbsky, James W.; Platts-Mills, Thomas A.E.; Cunningham-Rundles, Charlotte; Routes, John M.; Borish, Larry.

In: Journal of Clinical Immunology, Vol. 38, No. 3, 01.04.2018, p. 225-233.

Research output: Contribution to journalArticle

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T1 - Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID)

AU - Lawrence, Monica G.

AU - Palacios-Kibler, Thamiris V.

AU - Workman, Lisa J.

AU - Schuyler, Alexander J.

AU - Steinke, John W.

AU - Payne, Spencer C.

AU - McGowan, Emily C.

AU - Patrie, James

AU - Fuleihan, Ramsay L.

AU - Sullivan, Kathleen E.

AU - Lugar, Patricia L.

AU - Hernandez, Camellia L.

AU - Beakes, Douglas E.

AU - Verbsky, James W.

AU - Platts-Mills, Thomas A.E.

AU - Cunningham-Rundles, Charlotte

AU - Routes, John M.

AU - Borish, Larry

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N2 - Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9–5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6–85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.

AB - Although small prior studies have suggested that IgE can be low in common variable immunodeficiency (CVID), the workup for patients with recurrent infections and suspected hypogammaglobulinemia does not include the routine measurement of serum IgE. We sought to test the hypothesis that low/undetectable serum IgE is characteristic of CVID by comparing the frequency of low/undetectable serum IgE in healthy controls and patients with CVID. We measured total serum IgE in a large multi-center cohort of patients with CVID (n = 354) and compared this to large population-based cohorts of children and adults. We further compared IgE levels in patients with CVID to those with other forms of humoral immunodeficiency, and in a subset, measured levels of allergen-specific serum IgE and IgG subclasses. Lastly, we evaluated for the presence of IgE in commercially available immunoglobulin replacement therapy (IgRT) products. An undetectable serum IgE (< 2 IU/ml) occurs in only 3.3% (95% CI, 1.9–5.7%) of the general population. In contrast, an undetectable IgE occurs in 75.6% (95% CI, 65.6–85.7%) of patients with CVID. Conversely, a high IgE (> 180 IU/ml) is very uncommon in CVID (0.3% of patients). IgE is > 2 IU/ml in 91.2% of patients with secondary hypogammaglobulinemia, and thus, an IgE < LLOD is suggestive of a primary humoral immunodeficiency. Allergen-specific IgE is not detectable in 96.5% of patients with CVID. Sufficient quantities of IgE to change the total serum IgE are not contained in IgRT. The IgG1/IgG4 ratio is increased in subjects with low IgE, regardless of whether they are controls or have CVID. These findings support the routine measurement of serum IgE in the workup of patients with hypogammaglobulinemia.

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Lawrence MG, Palacios-Kibler TV, Workman LJ, Schuyler AJ, Steinke JW, Payne SC et al. Low Serum IgE Is a Sensitive and Specific Marker for Common Variable Immunodeficiency (CVID). Journal of Clinical Immunology. 2018 Apr 1;38(3):225-233. https://doi.org/10.1007/s10875-018-0476-0