嗜酸性粒细胞性胃炎(EG)是一种临床病理疾病,具有明显的胃嗜酸性粒细胞增多和临床症状。EG患者对更精确的诊断工具的需求尚未满足。
我们的目标是为EG开发基于组织和血液的诊断平台。
有EG的患者和没有EG的对照受试者被纳入9个嗜酸性粒细胞性胃肠道疾病研究人员相关的研究中心。分析了EG诊断组(EGDP;胃转录物子集)和EG血液生物标志物组(蛋白质多重阵列)。EGDP18评分来自18个高度失调的基因的表达,和血液EG评分来自失调的细胞因子/趋化因子水平。
来自185名受试者的胃活检标本和血液样本(EG患者,n=74;没有EG的对照组,n=111)进行了分析。EGDP(1)确定了活动性EG患者(P<0.0001,曲线下面积≥0.95),(2)有效监测纵向样本中的疾病活动(P=.0078),(3)在同一患者样本中高度相关(胃窦与身体,r=0.85,P<.0001),和(4)与胃峰嗜酸性粒细胞水平呈负相关(r=-0.83,P<0.0001),周围环状项圈(r=-0.73,P<0.0001),和内镜下结节(r=-0.45,P<0.0001)。对于基于血液的平台,eotaxin-3,胸腺和活化调节趋化因子,IL-5和胸腺基质淋巴细胞生成素水平显着升高。血液EG评分(1)区分EG患者与无EG的对照组(P<0.0001,曲线下面积≥0.91),(2)与胃嗜酸性粒细胞水平相关(血浆:r=0.72,P=.0002;血清:r=0.54,P=.0015),(3)与EGDP18评分呈负相关(血浆:r=-0.64,P=.0015;血清:r=-0.46,P=.0084)。血浆eotaxin-3水平与胃CCL26表达密切相关(r=0.81,P<0.0001)。
我们开发了基于组织和血液的平台,用于评估EG,并揭示了特定胃分子谱与组织学和内窥镜特征之间的强关联。为这种新兴的罕见疾病提供洞察力和临床准备工具。
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.
We aimed to develop tissue- and blood-based diagnostic platforms for EG.
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.
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).
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.