Clark S B, Rice T W, Tubbs R R, Richter J E, Goldblum J R
Center for Swallowing and Esophageal Disease and the Department of Anatomic Pathology, The Cleveland Clinic Foundation, Ohio, USA.
Am J Surg Pathol. 2000 Aug;24(8):1153-8. doi: 10.1097/00000478-200008000-00014.
Achalasia is an esophageal motor disorder characterized by abnormal relaxation of the lower esophageal sphincter and absence of progressive peristalsis in the esophageal body. Previous studies evaluating esophagomyotomy and esophageal resection specimens have shown the presence of myenteric inflammation to be a consistent and early pathologic change in patients with achalasia. Thus, the goal of this study was to determine the immunohistochemical characteristics of the inflammatory infiltrate within the myenteric plexus in patients with clinically early and end-stage achalasia. Using formalin-fixed tissue, we analyzed the immunohistochemical features of the myenteric lymphocytes using antibodies that recognize B cells (CD20), T cells (CD3), T cell subsets (CD8), and the activation state of T cell subpopulations (TIA-1 and granzyme B) in nine patients with clinically early achalasia who underwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine esophagomyotomy specimens was composed predominantly of T cells (CD3-positive), the majority of which also stained for CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal resection specimens, the myenteric infiltrate was composed predominantly of CD3-positive T cells in seven of 13 cases. In three cases, there was a predominance of CD20-positive B cells, and in the remaining three cases there were relatively equal numbers of T and B cells. In eight of 13 cases, the majority of T cells stained for CD8. TIA-1 immunoreactivity was found in the majority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy and esophageal resection specimens studied, rare granzyme B-positive cells were detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also CD8-positive, although the relative percentage of such cells appears to decrease with disease progression. Furthermore, many of the CD3-positive/CD8-positive myenteric lymphocytes also express TIA-1, suggesting they are resting or activated cytotoxic T cells. The immunohistochemical demonstration of granzyme B in a subpopulation of these cells supports the contention that achalasia is an immune-mediated disease, although the inciting antigen remains an enigma.
贲门失弛缓症是一种食管运动障碍性疾病，其特征为食管下括约肌异常松弛以及食管体部缺乏进行性蠕动。既往评估食管肌层切开术和食管切除标本的研究表明，肌间神经丛炎症是贲门失弛缓症患者一致且早期出现的病理变化。因此，本研究的目的是确定临床早期和终末期贲门失弛缓症患者肌间神经丛内炎性浸润的免疫组化特征。我们使用福尔马林固定组织，通过识别B细胞（CD20）、T细胞（CD3）、T细胞亚群（CD8）以及T细胞亚群激活状态（TIA-1和颗粒酶B）的抗体，分析了9例接受食管肌层切开术的临床早期贲门失弛缓症患者和13例接受食管切除术的临床终末期贲门失弛缓症患者肌间淋巴细胞的免疫组化特征。所有9例食管肌层切开术标本中的肌间浸润主要由T细胞（CD3阳性）组成，其中大多数也呈CD8染色阳性。在9例标本中的5例中，大多数CD8阳性细胞呈TIA-1染色阳性。在食管切除标本中，13例中有7例的肌间浸润主要由CD3阳性T细胞组成。3例中CD20阳性B细胞占优势，其余3例中T细胞和B细胞数量相对相等。13例中有8例的大多数T细胞呈CD8染色阳性。13例中有9例的大多数CD8阳性细胞检测到TIA-1免疫反应性。在所有研究的食管肌层切开术和食管切除标本中，均检测到罕见的颗粒酶B阳性细胞。总之，贲门失弛缓症患者的大多数肌间炎性细胞为CD3阳性T细胞，其中大多数也为CD8阳性，尽管此类细胞的相对百分比似乎随疾病进展而降低。此外，许多CD3阳性/CD8阳性肌间淋巴细胞也表达TIA-1，提示它们是静止或活化的细胞毒性T细胞。这些细胞亚群中颗粒酶B的免疫组化显示支持贲门失弛缓症是一种免疫介导疾病的观点，尽管引发抗原仍然是个谜。
