TY - JOUR
T1 - Molecular, endoscopic, histologic, and circulating biomarker-based diagnosis of eosinophilic gastritis
T2 - Multi-site study
AU - Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR)
AU - Shoda, Tetsuo
AU - Wen, Ting
AU - Caldwell, Julie M.
AU - Collins, Margaret H.
AU - Besse, John A.
AU - Osswald, Garrett A.
AU - Abonia, J. Pablo
AU - Arva, Nicoleta C.
AU - Atkins, Dan
AU - Capocelli, Kelley E.
AU - Dellon, Evan S.
AU - Falk, Gary W.
AU - Gonsalves, Nirmala
AU - Gupta, Sandeep K.
AU - Hirano, Ikuo
AU - Mukkada, Vincent A.
AU - Putnam, Philip E.
AU - Sheridan, Rachel M.
AU - Rudman Spergel, Amanda K.
AU - Spergel, Jonathan M.
AU - Wechsler, Joshua B.
AU - Yang, Guang Yu
AU - Aceves, Seema S.
AU - Furuta, Glenn T.
AU - Rothenberg, Marc E.
PY - 2020/1
Y1 - 2020/1
N2 - Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. Objective: We aimed to develop tissue- and blood-based diagnostic platforms for EG. Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers–associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P <.0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P =.0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P <.0001), and (4) inversely correlated with gastric peak eosinophil levels (r = −0.83, P <.0001), periglandular circumferential collars (r = −0.73, P <.0001), and endoscopic nodularity (r = −0.45, P <.0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P <.0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P =.0002; serum: r = 0.54, P =.0015), and (3) inversely correlated with EGDP18 scores (plasma: r = −0.64, P =.0015; serum: r = −0.46, P =.0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P <.0001). Conclusion: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.
AB - Background: Eosinophilic gastritis (EG) is a clinicopathologic disorder with marked gastric eosinophilia and clinical symptoms. There is an unmet need among patients with EG for more precise diagnostic tools. Objective: We aimed to develop tissue- and blood-based diagnostic platforms for EG. Methods: Patients with EG and control subjects without EG were enrolled across 9 Consortium of Eosinophilic Gastrointestinal Disease Researchers–associated sites. An EG Diagnostic Panel (EGDP; gastric transcript subset) and EG blood biomarker panel (protein multiplex array) were analyzed. EGDP18 scores were derived from the expression of 18 highly dysregulated genes, and blood EG scores were derived from dysregulated cytokine/chemokine levels. Results: Gastric biopsy specimens and blood samples from 185 subjects (patients with EG, n = 74; control subjects without EG, n = 111) were analyzed. The EGDP (1) identified patients with active EG (P <.0001, area under the curve ≥ 0.95), (2) effectively monitored disease activity in longitudinal samples (P =.0078), (3) highly correlated in same-patient samples (antrum vs body, r = 0.85, P <.0001), and (4) inversely correlated with gastric peak eosinophil levels (r = −0.83, P <.0001), periglandular circumferential collars (r = −0.73, P <.0001), and endoscopic nodularity (r = −0.45, P <.0001). For blood-based platforms, eotaxin-3, thymus and activation-regulated chemokine, IL-5, and thymic stromal lymphopoietin levels were significantly increased. Blood EG scores (1) distinguished patients with EG from control subjects without EG (P <.0001, area under the curve ≥ 0.91), (2) correlated with gastric eosinophil levels (plasma: r = 0.72, P =.0002; serum: r = 0.54, P =.0015), and (3) inversely correlated with EGDP18 scores (plasma: r = −0.64, P =.0015; serum: r = −0.46, P =.0084). Plasma eotaxin-3 levels strongly associated with gastric CCL26 expression (r = 0.81, P <.0001). Conclusion: We developed tissue- and blood-based platforms for assessment of EG and uncovered robust associations between specific gastric molecular profiles and histologic and endoscopic features, providing insight and clinical readiness tools for this emerging rare disease.
KW - Biomarker
KW - diagnostic panel
KW - eosinophil
KW - eosinophilic gastritis
KW - transcriptome
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U2 - 10.1016/j.jaci.2019.11.007
DO - 10.1016/j.jaci.2019.11.007
M3 - Article
C2 - 31738990
AN - SCOPUS:85075817687
VL - 145
SP - 255
EP - 269
JO - Journal of Allergy and Clinical Immunology
JF - Journal of Allergy and Clinical Immunology
SN - 0091-6749
IS - 1
ER -