Poor performance of anti-mitochondrial antibodies for the diagnosis of primary biliary cholangitis in female Colombian patients: A single-center study

Abstract

BACKGROUND Primary biliary cholangitis (PBC) is a serious disease that causes significant morbidity. PBC is confirmed with liver biopsy but autoantibodies are frequently used as proxies for diagnosis. The performance of autoantibodies for the diagnosis of PBC seems to vary widely across populations. AIM To assess the diagnostic performance of several autoantibodies for the diagnosis of PBC in Latin American individuals. METHODS We studied 85 female adult Colombians, 43 cases with biopsy-confirmed PBC and 42 controls in whom a liver biopsy ruled out PBC. Plasma anti-mitochondrial antibodies (AMAs), anti-smooth muscle antibodies (ASMAs) and anti-nuclear antibodies (ANAs), as well as total immunoglobulin (Ig) M and IgG were determined using immunofluorescence or enzyme-linked immunosorbent assay in all study participants within 1 year of the biopsy. For all variables, values analyzed were those closest to the date of the biopsy. Patients with viral or alcoholic hepatitis were excluded. RESULTS Mean age at diagnosis was 58.7 years for cases and 56.9 years for controls, and the body mass index was lower among cases. Most cases received ursodeoxycholic acid, while most controls received vitamin E. Sjögren syndrome and Hashimoto’s thyroiditis were the most frequent autoimmune comorbidities of PBC. The prevalence of AMA positivity among PBC cases was unexpectedly low. The sensitivity and specificity values were respectively 44.2% and 76.2% for AMA, 74.4% and 38.1% for ANA, 14.0% and 73.8% for ASMA, 26.7% and 80.0% for IgG, and 57.1% and 85.7% for IgM. The combination of positive AMA plus positive IgM had 91% positive predictive value for PBC. Among AMA-negative cases, the most prevalent antibodies were ANA (87.5%). In all, 62% of AMA-positive and 84.6% of IgM-positive individuals had fibrosis in their biopsy. CONCLUSION AMA positivity was very low among female Latin American patients with PBC. The performance of all antibodies was quite limited. These results highlight the urgent need for better PBC biomarkers.

Laboratory risk factors for coexistent primary biliary cholangitis in patients with Sjögren’s syndrome: a retrospective study

“…We found that the elevated IgM level was an independent risk factor for SS in patients with PBC, suggesting that clinicians should pay attention to IgM at an early stage of the disease. IgM is the primary immunoglobulin involved in the early immune response, and in patients with PBC, it is synthesized at high levels through T and B cell activation, reflected in higher serum concentrations [ 15 – 19 ]. Although there is a disorder in the peripheral B cell population of patients with SS [ 20 ], the abnormality of IgM mainly exists in the labial gland tissue [ 21 ], while immunological dysregulation in serum is related to IgG-producing clones rather than IgM-producing clones [ 22 ].…”

Diagnostic value of anti-mitochondrial antibody in patients with primary biliary cholangitis: A systemic review and meta-analysis

“…Despite the encouraging results, there was considerable variation in sensitivity (43.8%–100% for AMA detection, 52.0%–100% for M2 determination) and specificity (83.3%–100% for AMA detection, 76.5%–100% for M2 detection) across individual studies. [36–59] Heterogeneity is a potential problem in meta-analysis that can affect the validity of results in a systematic review and needs to be quantified. [60] Thus, we performed meta-regression based on the classification of sample size, ethnicity, study period, and detection assay for AMA and M2.…”