Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy

Benjamin L. Wright; Nielsen Q. Fernandez-Becker; Neeraja Kambham; Natasha Purington; Shu Cao; Dana Tupa; Wenming Zhang; Sayantani B. Sindher; Matthew A. Rank; Hirohito Kita; David A. Katzka; Kelly P. Shim; Bryan J. Bunning; Alfred D. Doyle; Elizabeth A. Jacobsen; Mindy Tsai; Scott D. Boyd; Monali Manohar; R. Sharon Chinthrajah

doi:10.1016/j.cgh.2020.05.019

Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy

Benjamin L. Wright, Nielsen Q. Fernandez-Becker, Neeraja Kambham, Natasha Purington, Shu Cao, Dana Tupa, Wenming Zhang, Sayantani B. Sindher, Matthew A. Rank, Hirohito Kita, David A. Katzka, Kelly P. Shim, Bryan J. Bunning, Alfred D. Doyle, Elizabeth A. Jacobsen, Mindy Tsai, Scott D. Boyd, Monali Manohar, R. Sharon Chinthrajah

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Abstract

Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. Results: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. Conclusions: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov

Original language	English (US)
Pages (from-to)	1151-1159.e14
Journal	Clinical Gastroenterology and Hepatology
Volume	19
Issue number	6
DOIs	https://doi.org/10.1016/j.cgh.2020.05.019
State	Published - Jun 2021

Keywords

EREFS
EoEHSS
Food Allergy
Inflammation

ASJC Scopus subject areas

Hepatology
Gastroenterology

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10.1016/j.cgh.2020.05.019

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Wright, B. L., Fernandez-Becker, N. Q., Kambham, N., Purington, N., Cao, S., Tupa, D., Zhang, W., Sindher, S. B., Rank, M. A., Kita, H., Katzka, D. A., Shim, K. P., Bunning, B. J., Doyle, A. D., Jacobsen, E. A., Tsai, M., Boyd, S. D., Manohar, M., & Chinthrajah, R. S. (2021). Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy. Clinical Gastroenterology and Hepatology, 19(6), 1151-1159.e14. https://doi.org/10.1016/j.cgh.2020.05.019

Wright, BL, Fernandez-Becker, NQ, Kambham, N, Purington, N, Cao, S, Tupa, D, Zhang, W, Sindher, SB, Rank, MA , Kita, H, Katzka, DA, Shim, KP, Bunning, BJ, Doyle, AD, Jacobsen, EA, Tsai, M, Boyd, SD, Manohar, M & Chinthrajah, RS 2021, 'Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy', Clinical Gastroenterology and Hepatology, vol. 19, no. 6, pp. 1151-1159.e14. https://doi.org/10.1016/j.cgh.2020.05.019

@article{67699fb1cce64eca9c26561ccbaff770,

title = "Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy",

abstract = "Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. Results: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. Conclusions: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov",

keywords = "EREFS, EoEHSS, Food Allergy, Inflammation",

author = "Wright, {Benjamin L.} and Fernandez-Becker, {Nielsen Q.} and Neeraja Kambham and Natasha Purington and Shu Cao and Dana Tupa and Wenming Zhang and Sindher, {Sayantani B.} and Rank, {Matthew A.} and Hirohito Kita and Katzka, {David A.} and Shim, {Kelly P.} and Bunning, {Bryan J.} and Doyle, {Alfred D.} and Jacobsen, {Elizabeth A.} and Mindy Tsai and Boyd, {Scott D.} and Monali Manohar and Chinthrajah, {R. Sharon}",

note = "Publisher Copyright: {\textcopyright} 2021 AGA Institute",

year = "2021",

month = jun,

doi = "10.1016/j.cgh.2020.05.019",

language = "English (US)",

volume = "19",

pages = "1151--1159.e14",

journal = "Clinical Gastroenterology and Hepatology",

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number = "6",

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TY - JOUR

T1 - Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy

AU - Wright, Benjamin L.

AU - Fernandez-Becker, Nielsen Q.

AU - Kambham, Neeraja

AU - Purington, Natasha

AU - Cao, Shu

AU - Tupa, Dana

AU - Zhang, Wenming

AU - Sindher, Sayantani B.

AU - Rank, Matthew A.

AU - Kita, Hirohito

AU - Katzka, David A.

AU - Shim, Kelly P.

AU - Bunning, Bryan J.

AU - Doyle, Alfred D.

AU - Jacobsen, Elizabeth A.

AU - Tsai, Mindy

AU - Boyd, Scott D.

AU - Manohar, Monali

AU - Chinthrajah, R. Sharon

PY - 2021/6

Y1 - 2021/6

N2 - Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. Results: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. Conclusions: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov

AB - Background & Aims: Gastrointestinal side effects are common during oral immunotherapy (OIT) and eosinophilic esophagitis (EoE) is a potential complication. We aimed to characterize eosinophilic gastrointestinal responses to peanut OIT, in which peanut protein is given orally, with incremental increases in dose over time. Methods: Twenty adults with IgE-mediated peanut allergy were randomly assigned to groups given peanut OIT (n = 15) or placebo (n = 5); 1 additional subject withdrew before randomization. Serial gastrointestinal biopsies were collected at baseline (n = 21, 0 weeks), following dose escalation (n = 10, 52 weeks), and during the maintenance phase (n = 11, 104 weeks). Endoscopic findings were characterized using the EoE endoscopic reference score. Biopsies were assessed for eosinophils per high-power field (eos/hpf) and other pathology features using EoE histologic scoring system scores. We performed immunohistochemical analyses of eosinophil peroxidase deposition, quantified using automated image analysis. Results: At baseline, no subjects reported current gastrointestinal symptoms. However, 3 of the 21 subjects (14%) had esophageal peak eosinophil counts ≥15 eos/hpf and all subjects had dilated intercellular spaces (DIS). OIT induced or exacerbated esophageal eosinophilia (EE) at 52 weeks in most subjects (peak eosinophil counts >5 eos/hpf in 6 of 7 patients [86%]; peak eosinophil counts ≥15 eos/hpf in 4 of 7 patients [57%]). One subject met clinicopathologic criteria for EoE and withdrew; no significant changes in esophageal peak eosinophil counts were observed in the placebo group. EE in the OIT group corresponded with significant increases in EoE histologic scoring system scores and deposition of eosinophil peroxidase. In 4 of 6 participants (67%), OIT-induced EE and gastrointestinal eosinophilia resolved by the end of the maintenance phase. Gastrointestinal symptoms were not clearly associated with EE or gastrointestinal eosinophilia. Conclusions: In this pilot study, we found that peanut OIT-induced EE and gastrointestinal eosinophilia are usually transient and are not always associated with gastrointestinal symptoms. Clinicaltrials.gov

KW - EREFS

KW - EoEHSS

KW - Food Allergy

KW - Inflammation

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SN - 1542-3565

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JF - Clinical Gastroenterology and Hepatology

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ER -

Gastrointestinal Eosinophil Responses in a Longitudinal, Randomized Trial of Peanut Oral Immunotherapy

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