title: Component-resolved analysis of IgA, IgE, and IgG4 during egg OIT identifies markers associated with sustained unresponsiveness.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.|Duke University Medical Center, Durham, NC, USA.
authors.forename: B L
authors.initials: BL
authors.lastname: Wright
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA. mike.kulis@unc.edu.
authors.forename: M
authors.initials: M
authors.lastname: Kulis
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Orgel
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: A W
authors.initials: AW
authors.lastname: Burks
authors.affiliation: The EMMES Corporation, Rockville, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Dawson
authors.affiliation: The EMMES Corporation, Rockville, MD, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Henning
authors.affiliation: University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock, AR, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Jones
authors.affiliation: Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: Wood
authors.affiliation: Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Sicherer
authors.affiliation: The EMMES Corporation, Rockville, MD, USA.
authors.forename: R W
authors.initials: RW
authors.lastname: Lindblad
authors.affiliation: The EMMES Corporation, Rockville, MD, USA.
authors.forename: D
authors.initials: D
authors.lastname: Stablein
authors.affiliation: National Jewish Health, Denver, CO, USA.
authors.forename: D Y M
authors.initials: DY
authors.lastname: Leung
authors.affiliation: University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: B P
authors.initials: BP
authors.lastname: Vickery
authors.affiliation: Icahn School of Medicine at Mt. Sinai, New York, NY, USA.
authors.forename: H A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D000284:Administration, Oral; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D015415:Biomarkers; D003888:Desensitization, Immunologic / Q000379:methods; D021181:Egg Hypersensitivity / Q000276:immunology* / Q000628:therapy*; D004531:Eggs / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008297:Male; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D000485:Allergens; D015415:Biomarkers; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007073:Immunoglobulin E
keywords: IgA; component testing; egg allergy; food allergy; oral immunotherapy