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.

Characterization of the B-cell receptor repertoires in peanut allergic subjects undergoing oral immunotherapy

“…3). These results were supported by the reports that Ara h 2-or eggspecific IgA and IgG in serum were increased at as early as 7 days or 3 months after starting the OIT [21,30]. In addition, the CDR3 sequences reported as Ara h 2-specific IgA and IgG were not observed in our analysis (Supplementary Tables 4-6) [21].…”

Low-Dose Oral Immunotherapy Using Low-Egg-Allergen Cookies for Severe Egg-Allergic Children Reduces Allergy Severity and Affects Allergen-Specific Antibodies in Serum

“…Several authors have reported on serum biomarkers to predict clinical outcomes [13,14]. Allergen-specific IgG 4 is the most frequently used serum biomarker in studies of OIT because it could inhibit allergen IgE binding to B cells [15], and increased it when oral desensitization was induced [2][3][4][5][6][7][8]14].…”

“…Allergen-specific IgG 4 is the most frequently used serum biomarker in studies of OIT because it could inhibit allergen IgE binding to B cells [15], and increased it when oral desensitization was induced [2][3][4][5][6][7][8]14]. Wright et al [14] reported that the ratio of serum OM-specific IgG 4 /OM-specific IgE was significantly higher in the group that achieved sustained unresponsiveness whereas this was not the case for OVA. Our results are consistent with theirs.…”

Food Allergy

“…The majority of oral immunotherapy-treated patients become desensitized, which provides protection from reactions to unintentional ingestion of small amounts of food allergen. However, this initial desensitization is dependent upon regular intake of the dose [37•]. Allergic reactions are common, particularly during the build-up phase of oral immunotherapy, and this may be due to the higher dose than is used in other approaches outlined below.…”