Primary biliary cirrhosis (PBC) with positive anti-mitochondrial antibody (AMA) and negative M2 subfraction – a cautionary tale

Introduction: PBC is almost invariably associated with M2-AMA positivity. We report a series of 4 patients who presented with a PBC-like syndrome, with positive AMA and invariably elevated IgM, in whom the M2 sub-fraction was negative by immunoblot technique. Subsequent external testing for M2 by ELISA was positive Methods: A retrospective review was performed on 4 patients with cholestatic liver blood tests, with positive AMA and negative M2 sub-fractions by immunoblot. Clinical, biochemical and immunological data was analysed. Results: *Biopsy consistent with PBC AMA Titre IGM Cholestatic SMA LKM ANF Titre Liver Elevated LBT's Biopsy Case 1 Yes 1:320 Yes Yes -ve -ve -ve Yes* Case 2 Yes 1:300 No Yes -ve -ve +ve 1:40 Yes* Case 3 Yes 1:320 Yes Yes -ve -ve -ve No Case 4 Yes 1:320 Yes Yes -ve -ve -ve No Conclusions: ELISA assay for detection of M2 sub-fractions in anti-mitochondrial antibody positive patients with PBC-like syndrome is the most sensitive and reliable laboratory technique currently available. Analysis by ELISA should be undertaken in all patients with positive AMA but apparently negative M2 sub-fractions, in whom PBC is strongly suspected clinically.