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Abstract：
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 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal 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%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and 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).
CONCLUSIONS: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem 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.
METHODS: Patients from 6 EoE centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastroesophageal 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%; and nonspecific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (interquartile range 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, and 62.2% year 6). Sequential RNA sequencing analyses revealed only 7 genes associated with this progression (with TSG6 and ALOX15 among the top 3 upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6 and 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).
CONCLUSIONS: Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes seem 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.
摘要：
背景：嗜酸细胞性食管炎（EoE）变种最近被表征为类似EoE的食管功能障碍症状，但没有明显的食管嗜酸性粒细胞增多。他们的病程和严重程度尚未确定。
方法：来自六个EoE中心的有食管功能障碍症状的患者，但包括食管活检中嗜酸性粒细胞峰值计数<15/hpf和至少一次随访没有胃食管反流病。临床,测定(免疫)-组织学和分子特征,并与EoE和健康对照进行比较。
结果：我们纳入了54例EoE变异型患者（EoE样食管炎53.7%；淋巴细胞性食管炎13.0%；非特异性食管炎33.3%）。在8例EoE样食管炎患者中，EoE的中位数为14个月（IQR3.6-37.6）。这种进展随着时间的推移而增加（第1年为17.6%，第3年为32.0%，第6年为62.2%）。序列RNA测序分析显示，只有7个与此进展相关的基因（TSG6和ALOX15在前三个上调基因中）与先前减弱的Th2途径上调。免疫染色证实了嗜酸性粒细胞相关蛋白（TSG6，ALOX15）的参与，并显示在进展期间GATA3阳性细胞的数量显着增加，表明Th1/Th2转换。从一个EoE变体（基线）到另一个变体（在随访期间）的转变为35.2％（中位观察时间为17.3个月）。
结论：EoE变异体转变为EoE提示存在疾病谱。似乎很少有基因与先前减弱的Th2信号的上调与EoE的进展有关。这些基因,包括GATA3作为Th1/Th2开关调节器，可能代表早期疾病发病机制的潜在治疗靶点。
方法：来自六个EoE中心的有食管功能障碍症状的患者，但包括食管活检中嗜酸性粒细胞峰值计数<15/hpf和至少一次随访没有胃食管反流病。临床,测定(免疫)-组织学和分子特征,并与EoE和健康对照进行比较。
结果：我们纳入了54例EoE变异型患者（EoE样食管炎53.7%；淋巴细胞性食管炎13.0%；非特异性食管炎33.3%）。在8例EoE样食管炎患者中，EoE的中位数为14个月（IQR3.6-37.6）。这种进展随着时间的推移而增加（第1年为17.6%，第3年为32.0%，第6年为62.2%）。序列RNA测序分析显示，只有7个与此进展相关的基因（TSG6和ALOX15在前三个上调基因中）与先前减弱的Th2途径上调。免疫染色证实了嗜酸性粒细胞相关蛋白（TSG6，ALOX15）的参与，并显示在进展期间GATA3阳性细胞的数量显着增加，表明Th1/Th2转换。从一个EoE变体（基线）到另一个变体（在随访期间）的转变为35.2％（中位观察时间为17.3个月）。
结论：EoE变异体转变为EoE提示存在疾病谱。似乎很少有基因与先前减弱的Th2信号的上调与EoE的进展有关。这些基因,包括GATA3作为Th1/Th2开关调节器，可能代表早期疾病发病机制的潜在治疗靶点。
