Sensitivity of AMA, however, although high, is limited. Investigators have reported patients who clinically, biochemically, and histologically have all the features of PBC despite consistently negative AMA testing both by immunofluorescence and with the most specific immunoblotting and immunoenzymatic techniques [38] [39] [40] [41] [42] . Overall, AMA seems to be negative in 5% of patients who otherwise have all the features typical for PBC [43] and an identical autoreactive CD4 T cell response to the critical autoantigen, PDC-E2 [44] . This small group of AMA-negative patients, however, may erroneously include patients with PBC-like symptoms induced by causes other than autoimmunity, such as patients with mutations in the ABCB4 (MDR3) gene [45] . These patients secrete reduced amounts of phospholipids into the bile, which is harmful to hepatocytes and cholangiocytes.