Food‐specific antibodies in oesophageal secretions: association with trigger foods in eosinophilic oesophagitis

Abstract

Summary Background Food antigens are clearly implicated in the induction and persistence of eosinophilic oesophagitis. Dietary elimination to identify triggers is tedious and expensive. Alternatives that can mitigate cost and improve patient quality of life during this process are needed. Aims To test the hypothesis that antibodies against foods that trigger eosinophilic oesophagitis are secreted into the oesophageal lumen where they can be collected by oesophageal brushings. Methods We evaluated food‐specific immune responses within brushings in 68 patients undergoing endoscopy (12 controls, 13 resolved eosinophilic oesophagitis and 43 active eosinophilic oesophagitis). Seventeen participants identified their trigger foods via food elimination diets. Immunoglobulin A and immunoglobulin G4 antibodies against the four most common eosinophilic oesophagitis food triggers were measured using the ImmunoCAP assay in the oesophageal brushings. Food‐specific antibody values were compared between active eosinophilic oesophagitis, resolved eosinophilic oesophagitis and controls. Results Patients with active eosinophilic oesophagitis (>15 eosinophils/hpf) demonstrated increased immunoglobulin A and immunoglobulin G4 levels to common eosinophilic oesophagitis triggers compared to controls (327 ± 380 vs 150 ± 130 for immunoglobulin A, and 1534 ± 3346 vs 178 ± 123 for immunoglobulin G4, P < 0.003). Specific trigger foods were associated with elevated immunoglobulin A and immunoglobulin G4 responses compared to foods that did not trigger oesophageal eosinophilia (733 ± 469 vs 142 ± 64, P < 0.001 immunoglobulin A and 2620 ± 3228 vs 526 ± 1050, P < 0.001 immunoglobulin G4). Conclusions Food‐specific antibodies are easily collected along the oesophageal lumen of eosinophilic oesophagitis patients. Further studies are needed to validate our preliminary findings to determine whether these antibodies can be used to guide elimination diet therapy.

Peripheral markers of allergen‐specific immune activation predict clinical allergy in eosinophilic esophagitis

“…Indeed, both disease activity and/or consumption of allergenic foods may influence total or antigen-specific IgG4 levels, as well as circulating memory T H 2cell responses. 21,22 Consistent with this, we found a higher degree of correlation between food-specific IgG4 levels and milk allergy when examining the subset of subjects that were consuming milk at the time of assay. Larger studies of the correlation between foodspecific IgG4 levels, clinical allergens, and disease activity in children are warranted.…”

“…Prior work has suggested that food-specific IgG4 levels in the serum and/or the esophagus may be a viable method to identify EoE-causal foods. [19][20][21][22] In our cohort, this approach had a relatively low sensitivity and specificity for distinguishing clinical EoE milk allergy. This could be due to the fact that we studied a pediatric cohort, assayed plasma antibody levels as opposed to those of esophageal tissue, or because most of the clinical EoE milk allergy subjects in this study were avoiding milk at the time of sample acquisition.…”

“…Events were gated by Lymphocytes, Live/Dead negative, CD8 − , CD19 − , CD3 + , CD4 + , CD45RA − , CD45RO + (Figure S2). As food-specific IgG4 levels have been shown to correlate with clinical EoE food allergy, 7,[19][20][21][22] we first examined total and milkspecific IgG4 levels in the plasma of control or clinical EoE milk allergy subjects. We did not observe a significant difference in total IgG4 levels (Figure 1A), but did observe a non-significant increase in milk-specific IgG4 levels in clinical EoE milk allergy subjects compared with controls (Figure 1B).…”

Eosinophils in Eosinophilic Esophagitis: The Road to Fibrostenosis is Paved With Good Intentions

“…Indeed, mice deficient for eosinophils have established that eosinophils support IgA production (50,88), which in turn, is secreted to the lumen to facilitate barrier function. Notably, food-specific IgA is increased in EoE (30). Finally, eosinophils expressing MHCII and CD80 have been identified in EoE subjects (191,192) and may present antigen to T cells.…”

“…For example, OIT induces food-specific IgA and IgG4 responses in saliva and peripheral blood (26,27). These markers are also increased in the saliva, biopsy homogenates and peripheral blood of patients with EoE (28)(29)(30). Importantly, food-specific IgA and IgG4 levels are associated with the development of sustained unresponsiveness to food challenge following OIT (27).…”