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In-depth proteomic profiles prior to symptom development in food protein-induced enterocolitis
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  • Yuzaburo Inoue,
  • Hironori Sato,
  • Masaki Ishikawa,
  • Yusuke Kawashima,
  • Hiroki Kawamura,
  • Mayumi Enseki,
  • Yuka Osaki,
  • Sachiko Kaburagi,
  • Masayuki Akashi,
  • Arisa Ito,
  • Eri Hayata,
  • Takeshi Yamamoto,
  • Taiji Nakano,
  • Soichiro Toda,
  • Yuki Okada,
  • Hiroaki Ito,
  • Daisuke Shigeta,
  • Yuki Tsumura,
  • Mariko Shimizu,
  • Minako Tomiita,
  • Yoshiyuki Yamada
Yuzaburo Inoue
Chiba University

Corresponding Author:[email protected]

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Hironori Sato
Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu Shoni Byotaigaku
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Masaki Ishikawa
Kazusa DNA Kenkyujo
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Yusuke Kawashima
Kazusa DNA Kenkyujo
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Hiroki Kawamura
Tokai University School of Medicine
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Mayumi Enseki
Tokai University School of Medicine
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Yuka Osaki
Keio University School of Medicine
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Sachiko Kaburagi
Keio University School of Medicine
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Masayuki Akashi
Keio University School of Medicine
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Arisa Ito
Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu Shoni Byotaigaku
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Eri Hayata
Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu Shoni Byotaigaku
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Takeshi Yamamoto
Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu Shoni Byotaigaku
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Taiji Nakano
Chiba Daigaku Daigakuin Igaku Kenkyuin Igakubu Shoni Byotaigaku
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Soichiro Toda
Kameda Sogo Byoin
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Yuki Okada
Kameda Sogo Byoin
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Hiroaki Ito
Kameda Sogo Byoin
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Daisuke Shigeta
Saku Iryo Center
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Yuki Tsumura
Keiyu Byoin
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Mariko Shimizu
Gunma Kenritsu Shoni Iryo Center
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Minako Tomiita
Chiba-ken Kodomo Byoin
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Yoshiyuki Yamada
Tokai University School of Medicine
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Abstract

not-yet-known not-yet-known not-yet-known unknown Background: The innate immune system is activated at the onset of food protein-induced enterocolitis syndrome (FPIES) symptoms. However, the precise mechanism through which this immune response is initiated remains unclear. Objective: We aimed to investigate the proteomic profile of FPIES during symptom development through in-depth serum and saliva proteomic analyses. Methods: We enrolled 17 patients with a previous diagnosis of egg yolk FPIES who underwent an oral food challenge test (OFC) with 5 g of heated egg yolk. Six patients showed positive OFC results, whereas 11 showed negative OFC results. Serum and saliva samples were collected before OFC and 1 and 2 h after ingestion. Serum was also collected at symptom onset. We analyzed serum and saliva peptides using data-independent acquisition-mass spectrometry and compared levels to identify protein groups and pathways important in FPIES symptom development. Results: We detected 4,138 and 7,202 proteins in the serum and saliva, respectively. The OFC-positive group exhibited 609 serum proteins with more than a two-fold change in expression 2 h after OFC, including proteasome subunits and neddylation-related proteins. We identified 304 proteins associated with symptom onset, including those related to the degradation response and neutrophil extracellular trap formation. Proteins related to neutrophil activation increased both in the serum and saliva, regardless of the onset of symptoms. Conclusion: Our findings suggest that changes in protein levels, including proteasome and neddylation-related proteins, may be involved in FPIES pathogenesis and warrant further investigation to address the growing clinical burden imposed by gastrointestinal allergies.