Hu YW, Tang P, Guo T, Wang ZF, Fang XC, Zhu LM, Fei GJ, Chen Y, Li XQ. Serum anti-enteric neuronal antibodies in patients with achalasia and their association with clinical profiles. World J Gastroenterol 2026; 32(36): 118689 [DOI: 10.3748/wjg.118689]
Corresponding Author of This Article
Xiao-Qing Li, MD, Professor, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. lixiaoqing20060417@126.com
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Gastroenterology & Hepatology
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Hu YW, Tang P, Guo T, Wang ZF, Fang XC, Zhu LM, Fei GJ, Chen Y, Li XQ. Serum anti-enteric neuronal antibodies in patients with achalasia and their association with clinical profiles. World J Gastroenterol 2026; 32(36): 118689 [DOI: 10.3748/wjg.118689]
World J Gastroenterol. Sep 28, 2026; 32(36): 118689 Published online Sep 28, 2026. doi: 10.3748/wjg.118689
Serum anti-enteric neuronal antibodies in patients with achalasia and their association with clinical profiles
Yao-Wen Hu, Pan Tang, Tao Guo, Zhi-Feng Wang, Xiu-Cai Fang, Li-Ming Zhu, Gui-Jun Fei, Yang Chen, Xiao-Qing Li
Yao-Wen Hu, Pan Tang, Tao Guo, Zhi-Feng Wang, Xiu-Cai Fang, Li-Ming Zhu, Gui-Jun Fei, Yang Chen, Xiao-Qing Li, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
Co-first authors: Yao-Wen Hu and Pan Tang.
Author contributions: Hu YW and Tang P contributed equally to this study, as they are co-first authors; Hu YW, Tang P, and Li XQ contributed to conceptualization and design; Hu YW, Tang P, Guo T, Wang ZF, Fang XC, Zhu LM, and Fei GJ contributed to data collection; Hu YW, Tang P, Guo T, Wang ZF, and Chen Y contributed to data analysis and interpretation; Li XQ conceived and supervised the study; and all authors contributed to manuscript drafting and revision and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81970476.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Peking Union Medical College Hospital (approval No. I-25PJ0734).
Clinical trial registration statement: The study was registered on the official website of clinical trials (https://clinicaltrials.gov, No. NCT07451301).
Informed consent statement: All participants provided written informed consent before enrolment in the study.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Data sharing statement: The datasets generated during and/or analyzed during the current study are available upon reasonable request from the corresponding author at lixiaoqing20060417@126.com.
Corresponding author: Xiao-Qing Li, MD, Professor, Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing 100730, China. lixiaoqing20060417@126.com
Received: January 19, 2026 Revised: March 10, 2026 Accepted: April 15, 2026 Published online: September 28, 2026 Processing time: 216 Days and 20.6 Hours
Abstract
BACKGROUND
Immune-mediated mechanisms are implicated in the pathogenesis of achalasia of cardia (AC), which is characterized by inflammation-driven degeneration of myenteric neurons. Circulating autoantibodies targeting the enteric nervous system may serve as potential biomarkers reflecting this underlying neurodegeneration. However, the clinical significance of anti-enteric neuronal antibodies (AENAs) in disease progression and treatment outcomes remains unexplored.
AIM
To evaluate the prevalence of AENA in AC and its correlation with clinical characteristics and treatment outcomes.
METHODS
This prospective cohort study included 97 patients with AC diagnosed according to the Chicago Classification version 4.0 and 98 age- and sex-matched healthy subjects (HS). Indirect immunofluorescence was used to detect AENA and antinuclear antibodies. Multivariable linear regression analyses were performed to explore associations between AENA intensity and clinical parameters in patients with AC.
RESULTS
The AENA-positive rate was significantly higher in patients with AC than HS (60.8% vs 25.5%, P < 0.001). AENA-positive patients had higher endoscopic CARS (contents, anatomy, resistance, and stasis) than AENA-negative patients (5.0 vs 4.0, P = 0.045), whereas Eckardt scores and manometric parameters did not differ between groups. Multivariable regression identified strong AENA positivity as independently associated with higher CARS (β = 0.95, 95% confidence interval: 0.37-1.53, P = 0.002), demonstrating a dose-response relationship (P for trend = 0.005). Patients with strong AENA intensity also exhibited greater barium column width and higher integrated relaxation pressure than those with moderate intensity. After peroral endoscopic myotomy and overlap weighting, AENA-positive patients had worse Eckardt scores at 1- and 6-month follow-up than AENA-negative patients (P = 0.031 and P = 0.005, respectively).
CONCLUSION
Serum AENA is prevalent in AC and correlates with disease severity in a dose-dependent manner and with early treatment response, potentially identifying patients with more severe disease characteristics and poorer outcomes.
Core Tip: Serum anti-enteric neuronal antibodies (AENA) are significantly more prevalent in patients with achalasia than in healthy subjects. This study identifies a novel dose-dependent association between AENA intensity and endoscopic disease severity, as assessed by the CARS (contents, anatomy, resistance, and stasis) score. Strong AENA positivity correlates with greater esophageal dilation and higher integrated relaxation pressure. Furthermore, AENA positivity is associated with less favorable symptomatic improvement after peroral endoscopic myotomy. These findings suggest that AENA status may serve as a valuable biomarker for identifying a more severe disease phenotype with poorer early treatment outcomes.
