Autonatibody against 70 kD heat shock protein in patients with autoimmune liver diseases

Abstract

Background/Aims: It has recently been suggested that heat shock proteins are implicated in the pathogenesis and the pathophysiology of various immunological disorders, and the presence of antibodies against heat shock proteins has been reported in several autoimmune diseases. Methods: We investigated autoantibodies against the two major human heat shock proteins (hsp70 and hsp90) in sera from patients with primary biliary cirrhosis and autoimmune hepatitis, the two major autoimmune liver diseases. Reactivity with human heat shock proteins obtained from phytohemagglutinin stimulated cells was investigated by immunoblots with sera at 1:20 dilution. Results: Reactivity with human hsp90 was not found in any sera from patients or normal controls. In contrast, reactivity with human hsp70 was found in 16 of 35 (45.7%) primary binary cirrhosis patients and in 9 of 17 (52.9%) autoimmune hepatitis patients, but similar reactivity was found in only 2 of 15 patients with chronic hepatitis B and 1 of 13 patients with chronic hepatitis C. All the normal controls showed a negative reaction. Two-dimensional immunoblots and immunoabsorption experiments established that the autoantibody recognized only human hsc70 (73 kD/pI 5.5), a constitutive form of the hsp70 family. Conclusions: Although the pathological significance of the autoantibody against hsc70 in these autoimmune liver diseases remains unknown, the serum autoantibody detected in primary biliary cirrhosis patients is closely related to clinical variables including serum total bilirubin, alanine aminotransferase, IgG, IgM, titers of antimitochondrial antibodies, and major symptoms (pruritus and/or icterus). These observations may suggest that the anti-hsc70 antibody is an indicator for the disease activity of primary biliary cirrhosis.