Immunoglobulin G4 in eosinophilic esophagitis : Immune complex formation and correlation with disease activity
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd..
BACKGROUND: Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co-localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits.
METHODS: This study included adult subjects with EoE (n = 13) and non-EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co-localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4-food protein interactions were confirmed with co-immunoprecipitation and mass spectrometry.
RESULTS: IgG4-CMP co-localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co-localization was also significantly higher in the active EoE group compared to non-EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil-derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain-14 in IgG4-enriched areas. Co-immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens.
CONCLUSION: These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
Allergy - 78(2023), 12 vom: 12. Dez., Seite 3193-3203 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Medernach, Jonathan G [VerfasserIn] |
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| Links: |
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| Themen: |
Allergens |
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| Anmerkungen: |
Date Completed 04.12.2023 Date Revised 15.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/all.15826 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 100 | 1 | |a Medernach, Jonathan G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Immunoglobulin G4 in eosinophilic esophagitis |b Immune complex formation and correlation with disease activity |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 15.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. | ||
| 520 | |a BACKGROUND: Recent studies have shown deposition of immunoglobulin G4 (IgG4) and food proteins in the esophageal mucosa of eosinophilic esophagitis (EoE) patients. Our aims were to assess whether co-localization of IgG4 and major cow's milk proteins (CMPs) was associated with EoE disease activity and to investigate the proteins enriched in proximity to IgG4 deposits | ||
| 520 | |a METHODS: This study included adult subjects with EoE (n = 13) and non-EoE controls (n = 5). Esophageal biopsies were immunofluorescence stained for IgG4 and CMPs. Co-localization in paired samples from active disease and remission was assessed and compared to controls. The proteome surrounding IgG4 deposits was evaluated by the novel technique, AutoSTOMP. IgG4-food protein interactions were confirmed with co-immunoprecipitation and mass spectrometry | ||
| 520 | |a RESULTS: IgG4-CMP co-localization was higher in the active EoE group compared to paired remission samples (Bos d 4, p = .02; Bos d 5, p = .002; Bos d 8, p = .002). Co-localization was also significantly higher in the active EoE group compared to non-EoE controls (Bos d 4, p = .0013; Bos d 5, p = .0007; Bos d 8, p = .0013). AutoSTOMP identified eosinophil-derived proteins (PRG 2 and 3, EPX, RNASE3) and calpain-14 in IgG4-enriched areas. Co-immunoprecipitation and mass spectrometry confirmed IgG4 binding to multiple food allergens | ||
| 520 | |a CONCLUSION: These findings further contribute to the understanding of the interaction of IgG4 with food antigens as it relates to EoE disease activity. These data strongly suggest the immune complex formation of IgG4 and major cow's milk proteins. These immune complexes may have a potential role in the pathophysiology of EoE by contributing to eosinophil activation and disease progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a eosinophilic esophagitis | |
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| 650 | 7 | |a Allergens |2 NLM | |
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| 700 | 1 | |a Li, Rung-Chi |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Xiao-Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Bocheng |e verfasserin |4 aut | |
| 700 | 1 | |a Noonan, Emily A |e verfasserin |4 aut | |
| 700 | 1 | |a Etter, Elaine F |e verfasserin |4 aut | |
| 700 | 1 | |a Raghavan, Shyam S |e verfasserin |4 aut | |
| 700 | 1 | |a Borish, Larry C |e verfasserin |4 aut | |
| 700 | 1 | |a Wilson, Jeffrey M |e verfasserin |4 aut | |
| 700 | 1 | |a Barnes, Barrett H |e verfasserin |4 aut | |
| 700 | 1 | |a Platts-Mills, Thomas A E |e verfasserin |4 aut | |
| 700 | 1 | |a Ewald, Sarah E |e verfasserin |4 aut | |
| 700 | 1 | |a Sauer, Bryan G |e verfasserin |4 aut | |
| 700 | 1 | |a McGowan, Emily C |e verfasserin |4 aut | |
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