Detection of autoantibody to aldolase B in sera from patients with troglitazone-induced liver dysfunction.
Troglitazone is a thiazolidinedione antidiabetic agent with insulin-sensitizing activities that was withdrawn from the market in 2000 due to its association with idiosyncratic hepatotoxicity. To address the suspected autoantibody production associated with troglitazone, we investigated autoantibodies in sera from patients with type II diabetes mellitus with troglitazone-induced liver dysfunction. Two female patients (47- and 70-year-old) ceased taking troglitazone (400 mg/day) after 23.5 and 16 weeks, respectively, due to increased serum ALT. Using two-dimensional electrophoresis and amino acid sequence analyses, aldolase B was identified as an autoantigen that reacted with antibodies in sera from both patients. The titer of anti-aldolase B remained high for several weeks after stopping troglitazone administration. The mean reactivity of autoantibodies to aldolase B determined by ELISA with sera of patients with chronic hepatitis (n = 40) and liver cirrhosis (n = 40) was significantly higher (p < 0.05 and p < 0.001, respectively) than with sera of healthy subjects (n = 80). These findings suggest that liver injury may cause the appearance of autoantibodies to aldolase B which may then aggravate the hepatitis. In addition, the anti-aldolase B titer might indicate the severity of liver dysfunction.
Maniratanachote
Rawiwan
R
Division of Drug Metabolism, Faculty of Pharmaceutical Sciences, Kanazawa University, Kanazawa 920-1192, Japan.
Shibata
Ayaka
A
Kaneko
Shuichi
S
Yamamori
Ikuo
I
Wakasugi
Takanobu
T
Sawazaki
Takeshi
T
Katoh
Kanefusa
K
Tokudome
Shogo
S
Nakajima
Miki
M
Yokoi
Tsuyoshi
T
D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000201:enzymology / Q000209:etiology / Q000276:immunology; D002839:Chromans / Q000009:adverse effects* / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005634:Fructose-Bisphosphate Aldolase / Q000276:immunology*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D015151:Immunoblotting; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000201:enzymology / Q000276:immunology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013347:Subcellular Fractions / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D000077288:Troglitazone
D001323:Autoantibodies; D002839:Chromans; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000410:Alanine Transaminase; D005634:Fructose-Bisphosphate Aldolase; D000077288:Troglitazone