The nature of the myenteric infiltrate in achalasia - An immunohistochemical analysis

Achalasia is an esophageal motor disorder characterized by abnormal relaxat ion of the lower esophageal sphincter and absence of progressive peristalsi s in the esophageal body. Previous studies evaluating esophagomyotomy acid esophageal resection specimens have shown the presence of myenteric inflamm ation to be a consistent and early pathologic change in patients with achal asia. 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 stare of T cell subpopulations (T IA-1 and granzyme B) in nine patients with clinically early achalasia who u nderwent esophagomyotomy and 13 patients with clinically endstage achalasia who underwent esophageal resection. The myenteric infiltrate in all nine e sophagomyotomy specimens was composed predominantly of T cells (CD3-positiv e), the majority of which also stained fur CD8. In five of nine specimens, the majority of CD8-positive cells stained for TIA-1. In the esophageal res ection specimens, the myenteric infiltrate was composed predominantly of CD 3-positive T cells in seven of 13 cases. In three cases, there was a predom inance of CD20-positive B cells, and in the remaining three cases there wer e relatively equal numbers of T and B cells. In eight of 13 cases, the majo rity of T cells stained for CD8. TIA-1 immunoreactivity was found in the ma jority of CD8-positive cells in nine of 13 cases. In all esophagomyotomy an d esophageal resection specimens studied, rare granzyme B-positive cells we re detected. In conclusion, the majority of myenteric inflammatory cells in patients with achalasia are CD3-positive T cells, most of which are also C D8-positive, although the relative percent age of such cells appears to dec rease with disease progression. Furthermore, many of the CD3-positive/CD8-p ositive myenteric lymphocytes also express TTA-1, suggesting they are resti ng 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 rema ins an enigma.