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

Clinical Trial

. 2016 Nov;71(11):1552-1560.

doi: 10.1111/all.12895. Epub 2016 Jun 13.

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Clinical Trial

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

B L Wright et al. Allergy. 2016 Nov.

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.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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Figures

FIGURE 1
FIGURE 1

Comparison of log transformed IgE-EW and IgE-OVM values between groups at baseline. Panel A depicts differences among groups for log IgE-EW. Panel B shows differences for log IgE-OVM. Statistical comparisons of baseline median values performed using exact 2-sided Wilcoxon unadjusted for multiplicity of tests.

FIGURE 2
FIGURE 2

Immunoglobulin trends for antigen-specific IgE, IgG4, IgA, IgA1, and IgA2 among groups. Responder status defined as passing a DBPCFC after at least 4 weeks off therapy at 22, 36 or 48 months. Graphs show logarithmic mean and SEM for each immunoglobulin measurement. Horizontal axis depicts time in months during the clinical trial.

FIGURE 3
FIGURE 3

Trends in endpoint-to-baseline log ratios between responders and non-responders. Graphs show logarithmic mean and SEM of endpoint-to-baseline ratios for serologic parameters with significant differences between responders and non-responders. Relative increases in the IgG4-EW (A), IgG4-OVM (B), IgA-EW (C), IgA2-EW (D), and the sum of IgG4-EW and IgA-EW (E) are depicted.

FIGURE 4
FIGURE 4

Log ratios of IgA, IgA1, IgA2 and IgG4 to IgE for EW, OVA and OVM in responders versus non-responders. Graphs show logarithmic mean and SE for ratios with significant differences between responders and non-responders. Ratios of IgG4:IgE, IgA:IgE, IgA2:IgE to EW and IgA:IgE to OVA have significant time by responder group interactions.

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