Retrospective Study
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 21, 2018; 24(3): 387-396
Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.387
Autoimmune liver disease-related autoantibodies in patients with biliary atresia
Shu-Yin Pang, Yu-Mei Dai, Rui-Zhong Zhang, Yi-Hao Chen, Xiao-Fang Peng, Jie Fu, Zheng-Rong Chen, Yun-Feng Liu, Li-Yuan Yang, Zhe Wen, Jia-Kang Yu, Hai-Ying Liu
Shu-Yin Pang, Yu-Mei Dai, Yi-Hao Chen, Yun-Feng Liu, Li-Yuan Yang, Hai-Ying Liu, Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
Rui-Zhong Zhang, Xiao-Fang Peng, Jie Fu, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
Zheng-Rong Chen, Department of Pathology, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
Zhe Wen, Jia-Kang Yu, Department of Neonatal Surgery, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong Province, China
Author contributions: Pang SY, Chen YH, Peng XF and Fu J performed the majority of experiments; Chen ZR reviewed the liver sections; Liu YF and Yang LY analyzed the data and contributed to editing of the manuscript; Wen Z and Yu JK collected all the clinical information; Pang SY, Dai YM, Zhang RZ and Liu HY designed the study and wrote the manuscript.
Supported by the Guangdong Provincial Science and Technology Planning Project, No. 2014A020212520; and the Guangzhou Science and Technology Project, No. 201707010014.
Institutional review board statement: The study protocol was approved by the Ethics Committee of Guangzhou Women and Children’s Medical Center, No. 2015090117.
Informed consent statement: Informed consent was obtained from the legal guardian of all patients prior to study enrolment.
Conflict-of-interest statement: The authors declare no conflict of interests related to this study.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Hai-Ying Liu, PhD, Chief Technician, Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, No. 9, Jinsui Road, Guangzhou 510623, Guangdong Province, China. xiangliuhaiying@aliyun.com
Telephone: +86-20-38076255 Fax: +86-20-38076255
Received: November 9, 2017
Peer-review started: November 9, 2017
First decision: November 30, 2017
Revised: December 14, 2017
Accepted: December 20, 2017
Article in press: December 20, 2017
Published online: January 21, 2018
Processing time: 71 Days and 5 Hours
Abstract
AIM

To investigate the prevalence and clinical significance of autoimmune liver disease (ALD)-related autoantibodies in patients with biliary atresia (BA).

METHODS

Sera of 124 BA patients and 140 age-matched non-BA controls were assayed for detection of the following autoantibodies: ALD profile and specific anti-nuclear antibodies (ANAs), by line-blot assay; ANA and anti-neutrophil cytoplasmic antibody (ANCA), by indirect immunofluorescence assay; specific ANCAs and anti-M2-3E, by enzyme linked immunosorbent assay. Associations of these autoantibodies with the clinical features of BA (i.e., cytomegalovirus infection, degree of liver fibrosis, and short-term prognosis of Kasai procedure) were evaluated by Spearman’s correlation coefficient.

RESULTS

The overall positive rate of serum autoantibodies in preoperative BA patients was 56.5%. ALD profile assay showed that the positive reaction to primary biliary cholangitis-related autoantibodies in BA patients was higher than that to autoimmune hepatitis-related autoantibodies. Among these autoantibodies, anti-BPO was detected more frequently in the BA patients than in the controls (14.8% vs 2.2%, P < 0.05). Accordingly, 32 (25.8%) of the 124 BA patients also showed a high positive reaction for anti-M2-3E. By comparison, the controls had a remarkably lower frequency of anti-M2-3E (P < 0.05), with 6/92 (8.6%) of patients with other liver diseases and 2/48 (4.2%) of healthy controls. The prevalence of ANA in BA patients was 11.3%, which was higher than that in disease controls (3.3%, P < 0.05), but the reactivity to specific ANAs was only 8.2%. The prevalence of ANCAs (ANCA or specific ANCAs) in BA patients was also remarkably higher than that in the healthy controls (37.9% vs 6.3%, P < 0.05), but showed no difference from that in patients with other cholestasis. ANCA positivity was closely associated with the occurrence of postoperative cholangitis (r = 0.61, P < 0.05), whereas none of the autoantibodies showed a correlation to cytomegalovirus infection or the stages of liver fibrosis.

CONCLUSION

High prevalence of autoantibodies in the BA developmental process strongly reveals the autoimmune-mediated pathogenesis. Serological ANCA positivity may be a useful predictive biomarker of postoperative cholangitis.

Keywords: Biliary atresia; Anti-nuclear antibody; Anti-neutrophilic cytoplasmic antibody; Autoimmune liver diseases; Autoantibodies

Core tip: The autoimmune-mediated pathogenesis of biliary atresia (BA) is not fully understood, and non-invasive diagnostic methods cannot clearly discriminate BA from other causes of neonatal cholestasis. We investigated the prevalence and clinical significance of autoimmune liver disease-related autoantibodies in BA patients. The overall positive rate of autoantibodies in BA was 56.5%. The data showed that frequent detection of autoantibodies in BA may strongly support the autoimmune-mediated pathogenesis. Interestingly, preoperative anti-neutrophil cytoplasmic antibody positivity was closely associated with prediction of cholangitis occurrence after Kasai portoenterostomy.