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	N/A	Yes*
Case 2	Yes	1:300	No	Yes	-ve	-ve	+ve	1:40	Yes*
Case 3	Yes	1:320	Yes	Yes	-ve	-ve	-ve	N/A	No
Case 4	Yes	1:320	Yes	Yes	-ve	-ve	-ve	N/A	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.