Targets of antibodies to soluble liver antigen in patients with autoimmune hepatitis.

To the Editor: Antibodies to a cytosolic soluble liver antigen (SLA), originally detected by an inhibition ELISA using cytosolic liver fractions and proposed as marker of a third type of autoimmune hepatitis (AIH) negative for other autoantibodies, have been also reported in anti-nuclear and/or -smooth muscle antibody type 1 AIH, liver kidney microsomaltype 2 AIH, and autoimmune sclerosing cholangitis (1–3). Anti-SLA is specific for these autoimmune liver diseases, in which it is associated with a more severe disease course, whereas it is virtually absent in nonhepatic autoimmune disorders (1–3). The target of anti-SLA has recently been identified by several groups as a UGA serine tRNA-associated protein complex [tRNP], through the screening of cDNA libraries (4– 6). On the basis that not all of the antiSLA-positive sera identified by inhibition ELISA react with tRNP and referring to studies indicating that SLA is a mixture of distinct antigens, Ballot et al. (7 ) questioned the identity of tRNP as the molecular target of anti-SLA antibodies. These investigators set out to reassess the matter, using anti-SLA-positive sera against rat liver cytosolic fraction in oneand two-dimensional immunoblotting analyses. Through peptide mass fingerprint analysis after matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry, the authors identified four isoforms of -enolase, a cytosolic enzyme of 50 kDa, as the major target of anti-SLA-positive sera. Volkmann et al. (8 ) questioned their proposal on both technical and clinical grounds. In their reply to Volkmann et al. (8 ), Johanet et al. (9 ) restated that the question of what is the major target of SLA remains open. Because anti-SLA is a specific serologic marker for autoimmune liver diseases and because of the wide availability of assays based on the use of recombinant SLA/liver pancreas (LP) polypeptide, the knowledge of whether SLA/LP is the correct antigen is of considerable clinical relevance. Not only does anti-SLA positivity identify patients with autoimmune liver disease, it also predicts a more severe course of the disease (2, 3). We would like to make a comment and give some experimental data: