Similar clinical outcome of AMA immunoblot-M2-negative compared to immunoblot-positive subjects over six years of follow-up

ABSTRACT

Background: The detection of anti-mitochondrial antibodies (AMA) is considered a hallmark in diagnosing primary biliary cholangitis (PBC). The most important AMA-subtype is AMA-M2 directed against the E2-subunit of pyruvate dehydrogenase. It is common clinical interpretation that lack of M2 due to immunoblotting (IB) indicates absence of specific auto-reactivity. We aimed to define whether M2-IB confirmation is linked to clinical outcomes.

Methods: Our cohort comprised 302 patients who tested positive for AMA with indirect immunofluorescence between 2006 and 2015. One hundred and eighty-four subjects (60.9%; male n = 29 [15.8%]) were tested M2-positive by confirmatory IB, whereas 118 subjects were IB-M2-negative (39.1%; male n = 25 [21.2%]). The natural history of 236 patients (78.1%) was evaluated by clinical follow-up (FU) assessing causes of death, leading health condition and response to PBC standard therapy if applicable.

Results: Mean time to FU was 6.8 years. Twenty-eight M2-positive patients (15.2% of 184) and 28 M2-negative patients (23.7% of 118) had died (p = 0.0958). Thirty-four M2-positives (18.5%) and 32 M2-negatives (27.1%) were not available for FU. According to the clinical course by the time of FU, subjects were allocated to one of four groups: a) 34 patients had known PBC with n = 16 having an adequate and 18 an inadequate treatment response, b) 1 de novo PBC was detected, c) 13 were AMA-positive without biochemical evidence of PBC and d) 9 subjects were tested AMA-negative at FU. These numbers were comparable to M2-positive subjects with similar long-term clinical outcome.

Conclusion: Our data suggest that the clinical value of confirmatory M2 immunoblotting in the diagnostic routine of PBC is overestimated as the clinical course appears not to be related to the test result.

KEYWORDS:

• PBC
• AMA
• biliary cholangitis
• anti-mitochondrial antibodies
• immunoblotting

Declaration of interest/other relationships

Authors have no conflicts of interest.

Reviewer disclosure

A reviewer of this manuscript has disclosed that they have been an investigator for a non-PBC clinical trial sponsored by Intercept (the manufacturer of an obeticholic acid, a licensed second-line drug for PBC). They have also received honoraria for CME lectures that were sponsored by Intercept-Canada. The other peer reviewers of this manuscript have no other relevant financial relationships or otherwise to disclose.

Authors’ contributions

SZ – Conceptualization, Formal Analysis, Visualization and Writing-Original Draft.

MS, AF, GS, GA, DN – Investigation and Writing- Review & Editing; BM, ML – Investigation, Resources and Writing- Review & Editing.

BP, CD – Resources and Writing-Review & Editing.

EA – Conceptualization, Methodology, Investigation, Project administration, Funding acquisition, Supervision and Writing- Original Draft and Review & Editing.

Additional information

Funding

The work was supported by the PMU Forschungsforderungsfonds (PMU-FFF) under Grant E-18/27/141-AIS; Intercept Pharmaceuticals under the Practice-to-Policy Health Awards Program.