Department of Surgery, Klinikum Rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
Institute of Pathology, Technical University of Munich, Munich, Germany.
Dig Dis. 2020;38(5):398-407. doi: 10.1159/000505910. Epub 2020 Mar 20.
Crohn's disease (CD) is characterized by relapsing intestinal inflammation. The anti-inflammatory protein annexin A1 (ANXA1) has been linked to inflammatory processes in the gut.
To examine ANXA1 expression patterns in the inflamed intestine of patients with CD and associate ANXA1 expression capacity with disease characteristics.
Surgical specimens of patients with CD operated between 2003 and 2015 were examined. Immunohistochemistry and immunofluorescence were performed to delineate ANXA1 expression. Those with pronounced ANXA1 expression were included in further analysis by qPCR. ANXA1 mRNA expression ratio of the inflamed to non-inflamed tissue was determined and defined as expression capacity of the tissue. Depending on their expression capacity, patients were divided into 2 groups (ANXA1-low vs. ANXA1-high), which were associated with clinical characteristics.
Immunohistochemical ANXA1 expression was localized in inflamed regions of the intestine. In immunofluorescence, ANXA1 costained with myeloperoxidase as neutrophil marker, CD4 and CD8 as T cell marker but not CD20 as B cell marker or CD68 as macrophage marker. In qPCR, ANXA1 mRNA expression was upregulated by 20-fold in inflamed to noninflamed tissues. Patients with higher intrinsic ANXA1 expression capacity had significantly less severity of inflammation. Furthermore, the ANXA1-high group had significantly more locally restricted disease (p = 0.0070), more stricturating disease (p = 0.0037), and was less frequently treated by preoperative steroid therapy (p = 0.030).
ANXA1 expression was strongly associated with intestinal inflammation and expressed in T cells and neutrophils of the CD tissues. Patients with higher intrinsic ANXA1 expression capacity of the inflamed tissue presented milder inflammatory changes and indolent clinical course.
克罗恩病（CD）的特征是反复发作的肠道炎症。抗炎蛋白膜联蛋白 A1（ANXA1）与肠道中的炎症过程有关。
研究 CD 患者炎症肠道中 ANXA1 的表达模式，并将 ANXA1 的表达能力与疾病特征相关联。
对 2003 年至 2015 年间接受手术的 CD 患者的手术标本进行检查。进行免疫组织化学和免疫荧光染色以描绘 ANXA1 的表达。对表达明显的 ANXA1 的患者进行 qPCR 进一步分析。确定炎症组织与非炎症组织的 ANXA1 mRNA 表达比率，并将其定义为组织的表达能力。根据其表达能力，将患者分为 2 组（ANXA1-低与 ANXA1-高），并与临床特征相关联。
免疫组织化学 ANXA1 表达定位于肠道的炎症区域。在免疫荧光中，ANXA1 与髓过氧化物酶（作为中性粒细胞标志物）、CD4 和 CD8（作为 T 细胞标志物）共同染色，但不与 CD20（作为 B 细胞标志物）或 CD68（作为巨噬细胞标志物）共同染色。在 qPCR 中，炎症组织中 ANXA1 mRNA 的表达上调了 20 倍。具有更高内在 ANXA1 表达能力的患者炎症严重程度显著降低。此外，ANXA1-高组的局部受限疾病明显更多（p = 0.0070），狭窄性疾病更多（p = 0.0037），术前皮质类固醇治疗的频率也较低（p = 0.030）。
ANXA1 的表达与肠道炎症密切相关，并且在 CD 组织中的 T 细胞和中性粒细胞中表达。具有更高内在 ANXA1 表达能力的炎症组织的患者表现出较轻的炎症变化和较惰性的临床病程。
