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

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, 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 non-responders. Between-group comparisons were made amongst active and placebo, as well as responders and non-responders.

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 non-responders (10.9 kU/L, n=18, p=0.010). Logistic regression analysis revealed 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 greater in responders (p= 0.024, 0.024, 0.029, respectively). Ratios of IgG4:IgE, IgA:IgE, IgA2:IgE for EW and IgA:IgE for OVA were significantly elevated among responders (p = 0.004, 0.009, 0.028, 0.008, respectively).

Conclusions

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