Meta-Analysis of Antinuclear Antibodies in the Diagnosis of Antimitochondrial Antibody-Negative Primary Biliary Cholangitis

Abstract

Objective. The diagnostic value of antinuclear antibodies (ANAs) including anti-gp210 and anti-sp100 for primary biliary cholangitis/cirrhosis (PBC) has been widely reported. However, their diagnostic performances for antimitochondrial antibody- (AMA-) negative PBC were less well elucidated. Therefore, the aim of the current meta-analysis was to evaluate the diagnostic accuracy of ANAs in patients with AMA-negative PBC. Materials and Methods. Literature on the diagnostic value of biomarkers for AMA-negative PBC was systematically searched in PubMed, MEDLINE, EMBASE, and the Cochrane Library. The qualities of the retrieved studies were assessed by the Quality Assessment of Diagnostic Accuracy Studies-version 2 (QUADAS-2) scale. Pooled sensitivity and specificity of the biomarkers were calculated with random-effects models. The areas under the summary receiver operating characteristic (AUSROC) curves were used to evaluate the overall diagnostic performance of ANAs. Results. A total of 11 studies (400 AMA-negative PBC patients and 6217 controls) were finally included in the meta-analysis. ANAs had an overall sensitivity of 27% (95% CI: 20%, 35%) and specificity of 98% (95% CI: 97%, 99%). The pooled sensitivities for anti-gp210 and anti-sp100 were 23% (95% CI: 13%, 37%) and 25% (95% CI: 13%, 43%), respectively, and their specificities were 99% (95% CI: 97%, 100%) and 97% (95% CI: 93%, 98%), respectively. Conclusions. ANAs exhibited high specificity but low sensitivity and therefore could be used as reliable biomarkers to reduce the necessity of liver histology.

Analysis of Autoantibodies against Promyelocytic Leukemia Nuclear Body Components and Biochemical Parameters in Sera of Patients with Primary Biliary Cholangitis

“…The co-localization of Sp100 and PML in nuclear dots suggests association of both proteins in multi-subunit complexes. ANAs are a relevant tool for diagnosis of PBC, especially in AMA-negative patients, and their high specificity for PBC has been confirmed in several reports [ 22 , 28 , 29 ]. The existence of anti-Sp100 antibodies in PBC patients was related with a negative course of the disease [ 8 ].…”

“…Data from Western and Southern Europe also confirmed the importance of anti-Sp100 and anti-PML specific antibodies in PBC patients [ 17 , 21 , 24 , 27 , 33 ], similarly to studies from North America [ 23 ]. Meta-analyses evaluating the diagnostic accuracy of anti-Sp100 antibodies showed high specificity (but low sensitivity), with the possibility of using them as biomarkers in PBC [ 19 , 28 ]. The sensitivities for anti-Sp100 or anti-PML, as well as anti-Sp140 detected in our study are also low, despite being highly specific for PBC.…”

Primary Sclerosing Cholangitis and Primary Biliary Cirrhosis Overlap Syndrome: A Review

“… 23 ANA directed at anti-Sp100 or anti-gp210 are considered to be PBC-specific (specificity of over 95%), but have low sensitivity. 23 In a meta-analysis conducted by Zhang et al , 36 it was noted that for the diagnosis of PBC, anti-gp210 had a sensitivity and specificity of 23% and 99%, along with anti-sp100, which had a sensitivity and specificity of 25% and 97%, respectively. Each of the 11 studies included in the meta-analysis had different inclusion criteria for their control groups, which raises concern regarding its effect on the validity of the study.…”

“…Each of the 11 studies included in the meta-analysis had different inclusion criteria for their control groups, which raises concern regarding its effect on the validity of the study. 36 …”

Changes of Serum IgG Glycosylation Patterns in Primary Biliary Cholangitis Patients

“…Antinuclear antibodies (ANAs) are present in approximately 50% of PBC patients, and their prevalence in AMA-negative sera reached approximately 85% (13). In the ANA category, research has shown that antinuclear dot antibodies sp100 and antinuclear pore antibodies gp210 are specific biomarkers in PBC serum (9,14,15), and they can reduce AMA-negative cases by less than 5% in PBC (16). The sensitivity of anti-sp100 and anti-gp210 for PBC was reported to be approximately 25% (9,15).…”