Esophageal type 2 cytokine expression heterogeneity in eosinophilic esophagitis in a multisite cohort

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:145

Article

Dunn, Julia L. M.¹  Shoda, Tetsuo¹  Caldwell, Julie M.¹  Wen, Ting¹  Aceves, Seema S.^2,3  Collins, Margaret H.¹⁶  Dellon, Evan S.^4,5  Falk, Gary W.⁶  Leung, John⁸  Martin, Lisa J.^9,10  Menard-Katcher, Paul¹¹  Rudman-Spergel, Amanda K.¹²  Spergel, Jonathan M.⁷  Wechsler, Joshua B.¹³  Yang, Guang-Yu¹⁴  Furuta, Glenn T.¹⁵  Rothenberg, Marc E.¹ 

[1] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Pediat,Div Allergy & Immunol, 3333 Burnet Ave, Cincinnati, OH 45229 USA

[2] Univ Calif San Diego, Div Allergy Immunol, San Diego, CA 92103 USA

[3] Rady Childrens Hosp, San Diego, CA USA

[4] Univ N Carolina, Sch Med, Ctr Esophageal Dis & Swallowing, Chapel Hill, NC 27515 USA

[5] Univ N Carolina, Sch Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27515 USA

[6] Hosp Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA

[7] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA

[8] Tufts Med Ctr, Div Gastroenterol, Boston, MA 02111 USA

[9] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH 45229 USA

[10] Univ Cincinnati, Coll Med, Cincinnati, OH 45229 USA

[11] Univ Colorado, Div Gastroenterol & Hepatol, Anschutz Med Campus, Boulder, CO 80309 USA

[12] NIAID, Allergy Asthma & Airway Biol Branch, Div Allergy Immunol & Transplantat, NIH, Rockville, MD USA

[13] Lurie Childrens Hosp Chicago, Div Gastroenterol Hepatol & Nutr, Chicago, IL USA

[14] Northwestern Univ Feinberg, Sch Med, Dept Pathol, Chicago, IL USA

[15] Univ Colorado, Sch Med, Gastrointestinal Eosinophil Dis Program, Childrens Hosp Colorado,Digest Hlth Inst, Aurora, CO USA

[16] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Dept Pediat,Div Pathol, Cincinnati, OH 45229 USA

关键词: Allergy;    cytokine;    eosinophil;    fibrosis;    IL-5;    IL-13;    inflammation;    precision medicine;    resolution;    T(H)2 cells;   

DOI  :  10.1016/j.jaci.2020.01.051

来源: Elsevier

【 摘 要 】

Background: There is strong evidence for a role of type 2 cytokines in the pathogenesis of eosinophilic esophagitis (EoE); however, heterogeneity in type 2 gene expression has not been examined. Objective: We examined type 2 immunity-associated gene expression in esophageal biopsy specimens, aiming to determine the degree of cytokine heterogeneity and its potential clinical significance. Methods: Patients (n = 312) were recruited from 10 sites associated with the Consortium of Eosinophilic Gastrointestinal Disease Researchers. In addition to histologic and endoscopic assessment, esophageal biopsy specimens were examined for expression of 96 genes within the EoE diagnostic panel. Results: Five subgroups of patients with active EoE were identified by unsupervised clustering based on expression of IL4, IL5, IL13, C-C motif chemokine ligand 26 (CCL26), thymic stromal lymphopoietin (TSLP), Charcot-Leyden crystal (CLC), C-C motif chemokine receptor 3 (CCR3), and CPA3. These groups differed in age (P<.02) and EoE diagnostic panel score (P < 1.08E-30) but not in eosinophil levels. The group V patients had the highest expression of IL5, TSLP, and CCL26 and genes associated with tissue remodeling, such as COL8A1, actin gamma-2 (ACTG2), and tetraspanin 12 (TSPAN12). IL5 and IL13 were highly expressed in group IV; however, groups IV and V differed in age (34 vs 14 years [P<.05]). Groups II and III, which exhibited intermediate expression of IL5 and CPA3, were differentiated by high TSLP and IL13 in group III. Conclusion: We observed heterogeneous type 2 gene expression among patients with active EoE. Type 2 gene overexpression was not directly proportional to disease features; this was especially true for tissue remodeling events. These findings highlight a clinical opportunity for leveraging molecular endotypes to implement personalized medicine in EoE.

【 授权许可】

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