Sulfite oxidase–a new antigen system in cryptogenic liver disorders?

In about 9% of patients with chronic liver disorders the etiology remains unknown (‘cryptogenic liver disease’), i.e. viral, metabolic or toxic processes are excluded, and typical autoimmune features as detected in autoimmune hepatitis or primary biliary cirrhosis such as antibodies to nuclei, actin, liver-pancreas antigen, liver-kidney microsomes or known mitochondrial proteins are absent. However, in former studies it was shown that some patients had antibodies against commercially available sulfite oxidase (SUOX) prepared from chicken liver (1).

Since this enzyme fraction was not available any more we wanted to confirm our previous results by testing patients’ sera against sulfite oxidase prepared by our own from chicken liver and recombinantly expressed in E. coli.

SUOX was isolated from chicken liver according to published methods, and also expression of the recombinant protein in E. coli was performed according to standard methods.

With sera from different patients with cryptogenic liver disorders at least three antibody patterns could be observed by Western blotting: 1) antibodies reacting with the recombinant SUOX and the SUOX prepared from chicken liver; 2) antibodies reacting with a pellet and supernatant of the preparation from chicken liver after acetone precipitation (ca. 65kDa) but not the recombinant antigen, 3) antibodies reacting only with the pellet after actone fractionation (ca. 15kDa) but not the recombinant SUOX.

These data indicate that at least a subgroup of patients with cryptogenic liver diseases may be characterized by new SUOX-associated antigen/antibody systems, indicating that they may comprise a new subclass of autoimmune liver disease. Further studies with respect to clinical relevance and antigen-structure (identification of the 65 and 15kD proteins, epitope-mapping etc.) have still to be performed.

Literatur: 1 Klein R. & Berg P.A. (1991) Anti-M4 antibodies in primary biliary cirrhosis react with sulphite oxidase, an enzyme of the mitochondrial inter-membrane space. Clin. Exp. Immunol. 84, 445.

Key words

antigen/antibody system - cryptogenic liver disease - sulfite oxidase