Autoantibodies associated with acute rejection after liver transplantationfor type-2 autoimmune hepatitis

Autoantibodies, markers of autoimmune diseases, can also be detected in chr onic allograft rejection. However, the appearance of these autoantibodies i n acute rejection after orthotopic liver transplantation has not yet been r eported, Liver-kidney-microsome type-1 (LKM-1) antibodies directed against the autoantigen cytochrome CYP2D6 define a group of patients with autoimmun e hepatitis type-2 (AIH-2), distinct from autoimmune hepatitis type-1 (AIH- 1) in which antinuclear antibodies and anti-smooth muscle antibodies (SMA) with actin specificity are present in patient sera. Autoantibodies were stu died by the quantitative CYP2D6 radioligand assay (RLA) that uses a radiola beled CYP2D6 as antigen, immunoblotting using recombinant CYP2D6 protein an d human liver microsomal and cytosolic fractions, and indirect immunofluore scence (IIF) using rat kidney-stomach-liver cryostat sections. In addition, the specificity of anti-SMA was detected by IIF on HEp2 cell line harveste d with colchicin. This report describes the time course of CYP2D6 antibodie s and the appearance of anti-SMA (without anti-actin, cytokeratin and vimen tin reactivity) associated with acute rejection during a 2-year follow-up, in a patient who underwent transplantation at end-stage type 2 autoimmune h epatitis. In addition, we report a new reactivity against an unknown 40-kDa protein using a rat cytosolic fraction. The detection of autoantibodies in sequential samples may be important to better predict rejection or relapse , and to establish adequate therapy.