Ovomucoid epitope‐specific repertoire of IgE, IgG₄, IgG₁, IgA₁, and IgD antibodies in egg‐allergic children

Abstract

Background: Egg-white ovomucoid, that is, Gal d 1, is associated with IgE-mediated allergic reactions in most egg-allergic children. Epitope-specific IgE levels have been correlated with the severity of egg allergy, while emerging evidence suggests that other antibody isotypes (IgG 1 , IgG 4 , IgA , and IgD) may have a protective function; yet, their epitope-specific repertoires and associations with atopic comorbidities have not been studied. Methods: Bead-based epitope assay (BBEA) was used to quantitate the levels of epitope-specific (es)IgA, esIgE, esIgD, esIgG 1 , and esIgG 4 antibodies directed at 58 (15-mer) overlapping peptides, covering the entire sequence of ovomucoid, in plasma of 38 egg-allergic and 6 atopic children. Intraclass correlation (ICC) and coefficient of variation (CV) were used for the reliability assessment. The relationships across esIgs were evaluated using network analysis; linear and logistic regressions were used to compare groups based on egg allergy status and comorbidities. Results: BBEA had high reliability (ICC >0.75) and low variability (CV <20%) and could detect known IgE-binding epitopes. Egg-allergic children had lower esIgA 1 (P = .010) and esIgG 1 (P = .016) and higher esIgE (P < .001) and esIgD (P = .015) levels compared to the atopic controls. Interestingly, within the allergic group, children with higher esIgD had decreased odds of anaphylactic reactions (OR =0.48, P = .038). Network analysis identified most associations between esIgE with either esIgG 4 or esIgD; indicating that IgE-secreting plasma cells could originate from either sequential isotype switch from antigen-experienced intermediate isotypes or directly from the IgD + B cells. Conclusions: Collectively, these data point toward a contribution of epitope-specific antibody repertoires to the pathogenesis of egg allergy.

Predicting probability of tolerating discrete amounts of peanut protein in allergic children using epitope‐specific IgE antibody profiling

“…Individual ses‐IgE antibodies had strong pairwise correlation between themselves (median rho = 0.85 [0.76, 0.87]), as we have observed previously 25 . Of all ses‐IgEs, 61 (95%) were negatively correlated with CTDs (Figure 2C).…”

Identification of Seasonal Variations of Antibodies against PR-10-Specific Epitopes Can Be Improved Using Peptide-Phage Display

“…This highlights the need of biomarkers to distinguish AIT responders from nonresponders [5]. Methods enabling the identification of personalized epitope profiles might become crucial for predicting severity of allergy, as associations between the intensity of clinical symptoms and the IgE epitope diversity and proximity for milk, peanut, and egg allergy were reported [8, 14]. The establishment of biomarkers to predict AIT outcome is challenging, due to the variety of processes occurring during desensitization, involving not only changes in IgE or IgE-blocking antibody titers [15].…”

“…There is solid knowledge regarding the epitope-binding profile of IgE and IgE-blocking antibodies elicited during AIT, but limited to only a few patients [16]. Robust methods are needed to study larger numbers of patients, which is essential since every patient has not only a different profile with respect to epitopes but also antibodies targeting the same epitope are from different classes [14, 16]. We used an improved method for in silico analysis of allergen-specific epitope motifs during natural allergen exposure, such as birch pollen.…”

EAACIMolecular Allergology User's Guide 2.0

“…Subsequently, the presumed protective effects of epitope‐specific IgG1/4, IgA, and IgD immune responses in relation to epitope‐specific IgE were investigated in individuals with a history of chicken egg allergy. Collectively higher ovamucoid epitope‐specific IgE and IgD together with lower IgA and IgG antibody levels as measured with a bead‐based epitope Luminex assay compared with atopic controls were shown to be important contributors to the pathogenesis of egg allergy 139,140 (49‐50). In the most definitive study to date, predictive performance of a peanut bead‐based epitope Luminex assay was evaluated using sera from subjects in the noninterventional arm of the LEAP trial, CoFAR2, and POISED clinical studies that used a double‐blind placebo‐controlled food challenge to document peanut allergy status.…”