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Clinicopathological study of primary biliary cirrhosis negative for antimitochondrial antibodies
1Department of Pathology (II), Kanazawa University School of Medicine, Japan.
Abstract:
Primary biliary cirrhosis (PBC) is characterized by the occurrence of antimitochondrial antibodies (AMA) and the progressive destruction of intrahepatic bile ducts, followed by biliary cirrhosis. However, there are about 5% of PBC patients who show clinicopathological features of PBC but are negative for AMA. In this study, clinicopathological features, as well as antibody reactivity against recombinant (r)-mitochondrial polypeptides, were examined in 30 AMA negative PBC patients and 38 AMA positive PBC patients, in whom the presence of AMA had been determined by indirect immunofluorescence (IF). There were few differences in the clinical and serological features between both groups. Histopathologic features, including staging, bile duct lesions and granuloma, were also similar in both groups. Among the 30 IF-tested AMA negative patients, 29 were also negative against beef heart mitochondrial proteins, but 24 reacted to one or more of the following r-polypeptides, as determined by immunoblotting: E1 alpha of pyruvate dehydrogenase complex, the E2 subunit of pyruvate dehydrogenase complex, and the branched-chain 2-oxo-acid dehydrogenase complex. The remaining six AMA-negative patients were asymptomatic, and histologically resembled having stage 1 of the disease, with relatively mild lymphocytic piecemeal necrosis. One case was positive for anti-smooth muscle antibody. The other clinicopathological features of these patients were similar to those of other AMA negative patients. The present study found that a majority of the AMA-negative patients fulfilling other clinicopathological criteria of PBC, had features similar to the AMA-positive PBC patients, and that a majority of IF AMA-negative patients were positive for r-polypeptides of the 2-oxo-acid dehydrogenase complex. It seems that nearly all the AMA negative patients possess a broad spectrum of antibody profile of AMA, in addition to clinicopathological and serological features.
Insights
Most patients with primary biliary cirrhosis (PBC) negative for antimitochondrial antibodies (AMA) still show PBC features and react to specific mitochondrial proteins. This suggests a broader antibody profile in AMA-negative PBC patients.
Area of Science:
- Immunology
- Hepatology
- Autoimmunity
Background:
- Primary biliary cirrhosis (PBC) is an autoimmune liver disease characterized by antimitochondrial antibodies (AMA) and bile duct destruction.
- A subset of PBC patients (~5%) present with PBC features but lack AMA detectable by indirect immunofluorescence (IF).
- The clinical and immunological significance of AMA-negative PBC remains incompletely understood.
Purpose of the Study:
- To investigate the clinicopathological features of AMA-negative PBC patients.
- To examine antibody reactivity against recombinant (r)-mitochondrial polypeptides in AMA-negative PBC patients.
- To compare AMA-negative and AMA-positive PBC patient groups.
Main Methods:
- Clinicopathological data were collected from 30 AMA-negative and 38 AMA-positive PBC patients.
- AMA presence was confirmed by indirect immunofluorescence (IF).
- Antibody reactivity against specific recombinant mitochondrial polypeptides (E1 alpha of pyruvate dehydrogenase complex, E2 subunit of pyruvate dehydrogenase complex, branched-chain 2-oxo-acid dehydrogenase complex) was assessed by immunoblotting.
Main Results:
- AMA-negative and AMA-positive PBC groups showed minimal differences in clinical, serological, and histopathological features.
- Among 30 IF-tested AMA-negative PBC patients, 24 reacted to at least one recombinant mitochondrial polypeptide, primarily those of the 2-oxo-acid dehydrogenase complex.
- Six AMA-negative patients were asymptomatic with early-stage histological findings, one of whom had anti-smooth muscle antibody.
Conclusions:
- The majority of AMA-negative PBC patients exhibit clinicopathological and serological similarities to AMA-positive PBC patients.
- Most AMA-negative PBC patients demonstrate reactivity to specific recombinant mitochondrial polypeptides, particularly those of the 2-oxo-acid dehydrogenase complex.
- These findings suggest that AMA-negative PBC patients possess a broad spectrum of autoantibody profiles, aligning with the overall characteristics of PBC.