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Low serum IgE levels are a key indicator for common variable immunodeficiency (CVID), a primary humoral immunodeficiency. Routine IgE measurement can aid in diagnosing CVID in patients with recurrent infections and hypogammaglobulinemia.

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Area of Science:

  • Immunology
  • Clinical Medicine

Background:

  • Recurrent infections and hypogammaglobulinemia prompt investigation for immunodeficiencies.
  • Current diagnostic workups for suspected hypogammaglobulinemia do not routinely include serum IgE measurement.
  • Prior small studies suggested low IgE in common variable immunodeficiency (CVID).

Purpose of the Study:

  • To test the hypothesis that low/undetectable serum IgE is characteristic of CVID.
  • To compare the frequency of low/undetectable serum IgE in healthy controls and CVID patients.
  • To evaluate the utility of serum IgE in diagnosing primary humoral immunodeficiencies.

Main Methods:

  • Measured total serum IgE in a large multi-center cohort of CVID patients (n=354).
  • Compared IgE levels to large population-based cohorts of children and adults.
  • Compared IgE levels in CVID patients to those with other humoral immunodeficiencies.
  • Measured allergen-specific IgE and IgG subclasses in a subset of patients.
  • Evaluated for IgE presence in commercial immunoglobulin replacement therapy (IgRT) products.

Main Results:

  • Undetectable serum IgE (<2 IU/ml) occurs in 75.6% of CVID patients, versus 3.3% in the general population.
  • High IgE (>180 IU/ml) is rare in CVID (0.3%).
  • IgE < LLOD is suggestive of primary humoral immunodeficiency, unlike secondary hypogammaglobulinemia (91.2% have IgE >2 IU/ml).
  • Allergen-specific IgE is undetectable in 96.5% of CVID patients.
  • IgRT products do not contain significant IgE levels.
  • Increased IgG1/IgG4 ratio observed in subjects with low IgE, irrespective of CVID status.

Conclusions:

  • Low/undetectable serum IgE is highly characteristic of CVID.
  • Serum IgE measurement should be routinely included in the workup of hypogammaglobulinemia.
  • Distinguishing primary from secondary hypogammaglobulinemia can be aided by IgE levels.
  • The findings support IgE as a valuable biomarker for diagnosing CVID.