A cross‐sectional study reveals a chronic low‐grade inflammation in achalasia

• Published in: Journal of gastroenterology and hepatology Vol. 38; no. 4; pp. 598 - 608
• Main Authors: Ma, Li‐Yun, Liu, Zu‐Qiang, Chen, Wei‐Feng, Yao, Lu, Zhong, Yun‐Shi, Zhang, Yi‐Qun, Ma, Li‐Li, Qin, Wen‐Zhen, Hu, Jian‐Wei, Cai, Ming‐Yan, Zhang, Zhen, Lin, Sheng‐Li, Hu, Hao, Zhou, Ping‐Hong, Li, Quan‐Lin
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01-04-2023
• Subjects: Achalasia; Autoimmune diseases; Blood Cell Count; CD8 antigen; CD8+ T cells; chronic inflammation; Cross-Sectional Studies; Esophageal Achalasia - pathology; Esophageal sphincter; Esophageal Sphincter, Lower - pathology; Flow cytometry; Globulins; Humans; Immune status; Immunofluorescence; Infiltration; Inflammation; Inflammation - pathology; Interleukin 6; Lymphocytes; Lymphocytes T; Manometry; Peripheral blood; Sequence analysis; Sphincter; transcriptome changes; Transcriptomes; transcriptome changes; CD8+ T cells; achalasia; chronic inflammation
• ISSN: 0815-9319; 1440-1746
• DOI: 10.1111/jgh.16091

Background and Aim
Immune‐mediated neuroinflammation has been proposed to underlie the loss of lower esophageal sphincter (LES) myenteric neurons in achalasia. However, the immune status and key pathogenic immune subpopulations remain unclear. This study aims to evaluate the inflammatory status of patients with achalasia and their correlation with clinical characteristics, and further explore the key pathogenic subpopulations.
Methods
We investigated the complete blood cell count and inflammatory markers in a large population of patients with achalasia (n = 341) and healthy controls (n = 80). The subpopulations of lymphocytes were analyzed by flow cytometry. Immunofluorescence was used to determine immune cell infiltration in the LES. Transcriptome changes of the key subpopulation were determined by RNA sequencing analysis.
Results
NLR, MLR, CRP, globulin, IL‐6 and IL‐10 were significantly elevated in patients with achalasia. MLR and globulin were positively correlated with disease duration. The absolute count and percentage of CD8+ T cells in peripheral blood and its infiltration around ganglion in the LES were significantly increased in achalasia. Transcriptome analysis indicated that CD8+ T cells were activated and proliferative. In addition to multiple inflammatory pathways, regulation of neuroinflammatory response pathway was also significantly up‐regulated in achalasia. GSEA analysis revealed a close association with autoimmune diseases.
Conclusions
Patients with achalasia suffered from chronic low‐grade inflammation with dysregulated immune cells and mediators associated with disease duration. CD8+ T cells might be the key pathogenic subpopulation of achalasia. Our results provide an important immune cell signature of the pathogenesis of achalasia.