A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to EOE over Time.

Greuter, Thomas; Straumann, Alex; Fernández Marrero, Yuniel; Germic, Nina; Hosseini, Aref; Chanwangpong, Apinya; Yousefi, Shida; Simon, Dagmar; Collins, Margaret H; Bussmann, Christian; Chehade, Mirna; Dellon, Evan S; Furuta, Glenn T; Gonsalves, Nirmala; Hirano, Ikuo; Moawad, Fouad J; Biedermann, Luc; Safroneeva, Ekaterina; Schoepfer, Alain M and Simon, Hans-Uwe (2024). A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to EOE over Time. Clinical and translational gastroenterology, 15(4), e00664. Wolters Kluwer Health 10.14309/ctg.0000000000000664

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BACKGROUND

Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.

METHODS

Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastro-esophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)-histological and molecular features were determined and compared with EoE and healthy controls.

RESULTS

We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; non-specific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (IQR 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, 62.2% year 6). Sequential RNA sequencing analyses revealed only seven genes associated with this progression (with TSG6 and ALOX15 among the top three upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6, ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).

CONCLUSION

Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes appear to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Dermatology

UniBE Contributor:

Fernández Marrero, Yuniel, Germic, Nina, Hosseini, Aref, Chanwangpong, Apinya, Yousefi, Shida, Simon, Dagmar, Safroneeva, Ekaterina, Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

2155-384X

Publisher:

Wolters Kluwer Health

Language:

English

Submitter:

Pubmed Import

Date Deposited:

07 Feb 2024 07:43

Last Modified:

02 May 2024 13:25

Publisher DOI:

10.14309/ctg.0000000000000664

PubMed ID:

38318864

BORIS DOI:

10.48350/192642

URI:

https://boris.unibe.ch/id/eprint/192642

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