Related Experiment Videos
Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients with primary biliary cirrhosis
1Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan.
Abstract:
Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.
Insights
Antimitochondrial antibody (AMA) levels in primary biliary cirrhosis (PBC) correlate with the number of targeted inner mitochondrial membrane proteins. Lower antibody counts against M2 proteins may lead to false-negative AMA tests in PBC patients.
Area of Science:
- Immunology
- Hepatology
- Autoimmunity
Background:
- Antimitochondrial auto-antibodies (AMA) are characteristic of primary biliary cirrhosis (PBC).
- A discrepancy exists between AMA positivity and anti-M2 auto-antibody reactivity in PBC patients.
- The diagnostic significance of this discrepancy requires further investigation.
Purpose of the Study:
- To investigate the relationship between AMA titer and immunoreactivity to specific M2 proteins in PBC patients.
- To explore the reasons for AMA negativity in some PBC cases.
- To understand the factors influencing AMA titer in PBC.
Main Methods:
- Indirect immunofluorescence was used to determine AMA titer.
- Immunoblot analysis assessed immunoreactivity to four M2 proteins (70, 50, 47, and 40 kDa).
- Analysis included 129 patients with confirmed PBC.
Main Results:
- AMA positivity was observed in 88% of PBC patients.
- All patients exhibited anti-M2 auto-antibodies to at least one M2 protein.
- AMA-negative patients often had antibodies to only one M2 protein, while high-titer AMA patients recognized multiple M2 proteins.
- A significant correlation was found between AMA titer and the number of antibodies to M2 proteins (P < 0.01).
Conclusions:
- AMA titer in PBC is influenced by the breadth of the antibody response to M2 proteins, not just their immunogenicity.
- Reduced immunoreactivity to multiple M2 proteins may result in AMA-negative PBC.
- These findings clarify the discrepancy between AMA and anti-M2 antibody status in PBC.