Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness

Allergy. 2016 Nov;71(11):1552-1560. doi: 10.1111/all.12895. Epub 2016 Jun 13.

Abstract

Background: In a previously reported CoFAR study, 55 subjects with egg allergy underwent randomized, placebo-controlled egg oral immunotherapy (eOIT). Active treatment induced desensitization in most and sustained unresponsiveness (SU) in a smaller subset. We hypothesized that component-resolved analysis of IgE, IgG4, IgA, IgA1, and IgA2 may identify potential biomarkers of SU in OIT subjects.

Methods: Longitudinal samples for 51 egg-allergic subjects (37 active and 14 placebo) were available. Egg white (EW)-, ovalbumin (OVA)-, and ovomucoid (OVM)-specific levels of IgA, IgA1, and IgA2 were quantified by ELISA. IgE and IgG4 to these antigens were quantified using ImmunoCAP® . Clinical responders achieved SU to egg; all others were considered nonresponders. Between-group comparisons were made among active and placebo, as well as responders and nonresponders.

Results: No placebo subjects achieved responder status. Through month 48, among the 37 active subjects, baseline IgE-OVM was lower in responders (median 3.97 kU/l, n = 19) than in nonresponders (10.9 kU/l, n = 18, P = 0.010). Logistic regression analysis revealed that lower baseline IgE-EW (P = 0.038), IgE-OVM (P = 0.032), and a higher IgG4/IgE-OVM ratio (P = 0.013) were associated with clinical response. Relative increases in IgG4-EW, IgA-EW, and IgA2-EW were observed in responders (P = 0.024, 0.024, and 0.029, respectively). IgG4/IgE, IgA/IgE, and IgA2/IgE ratios for EW and IgA/IgE ratio for OVA were found to be significantly elevated among responders (P = 0.004, 0.009, 0.028, and 0.008, respectively).

Conclusions: Increased IgG4-EW, IgA-EW, and IgA2-EW during eOIT are associated with clinical response to eOIT. Lower pretreatment IgE-EW and IgE-OVM are also associated with SU. Future studies are needed to evaluate and validate these potential biomarkers.

Keywords: IgA; component testing; egg allergy; food allergy; oral immunotherapy.

Publication types

  • Clinical Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Administration, Oral
  • Allergens / administration & dosage
  • Allergens / immunology*
  • Biomarkers
  • Desensitization, Immunologic* / methods
  • Egg Hypersensitivity / immunology*
  • Egg Hypersensitivity / therapy*
  • Eggs / adverse effects*
  • Female
  • Humans
  • Immunoglobulin A / blood
  • Immunoglobulin A / immunology*
  • Immunoglobulin E / blood
  • Immunoglobulin E / immunology*
  • Immunoglobulin G / blood
  • Immunoglobulin G / immunology*
  • Male
  • Treatment Failure
  • Treatment Outcome

Substances

  • Allergens
  • Biomarkers
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin E