AUTOANTIBODY AGAINST 70 KD HEAT-SHOCK PROTEIN IN PATIENTS WITH AUTOIMMUNE LIVER-DISEASES

Background/Aims: It has recently been suggested that heat shock protei ns are implicated in the pathogenesis and the pathophysiology of vario us immunological disorders, and the presence of antibodies against hea t shock proteins has been reported in several autoimmune diseases. Met hods: We investigated autoantibodies against the two major human heat shock proteins (hsp70 and hsp90) in sera from patients with primary bi liary cirrhosis and autoimmune hepatitis, the two major autoimmune liv er diseases. Reactivity with human heat shock proteins obtained from p hytohemagglutinin stimulated cells was investigated by immunoblots wit h sera at 1:20 dilution. Results: Reactivity with human hsp90 was not found in any sera from patients or normal controls, In contrast, react ivity with human hsp70 was found in 16 of 35 (45.7%) primary biliary c irrhosis patients and in 9 of 17 (52.9%) autoimmune hepatitis patients , but similar reactivity was found in only 2 of 15 patients with chron ic hepatitis B and 1 of 13 patients with chronic hepatitis C. All the normal controls showed a negative reaction, Two-dimensional immunoblot s and immunoabsorption experiments established that the autoantibody r ecognized only human hsc70 (73 kD/pI 5.5), a constitutive form of the hsp70 family. Conclusions: Although the pathological significance of t he autoantibody against hsc70 in these autoimmune liver diseases remai ns unknown, the serum autoantibody detected in primary biliary cirrhos is patients is closely related to clinical variables including serum t otal bilirubin, alanine aminotransferase, IgG, IgM, titers of antimito chondrial antibodies, and major symptoms (pruritus and/or icterus). Th ese observations may suggest that the anti-hsc70 antibody is an indica tor for the disease activity of primary biliary cirrhosis.