Published online Jan 21, 2018. doi: 10.3748/wjg.v24.i3.387
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
To investigate the prevalence and clinical significance of autoimmune liver disease (ALD)-related autoantibodies in patients with biliary atresia (BA).
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.
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.
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.
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.