Weinvestigatedthe specificity of various autoantibodies in antimitochondrial antibody (AMA)-negative patients with primary biliary cirrhosis (PBC). Weexamined sera from 144 patients with PBC, 17 of whomwere AMAnegative by indirect immunofluorescence. The AMAnegative group showed a significantly higher positivity for smooth muscle antibody, but not for antinuclear antibody, as compared with the AMA-positive group. IgG class anti-PDH by enzymelinked immunosorbent assay (ELISA) were detected in 13 % of the AMA-negative group. However, all PBC patients showed positive IgG, IgA, and/or IgM class anti-M2 to the four M2 proteins by immunoblotting. These results suggest that the detection of IgG and IgMclass anti-PDH and that of antibodies to the four M2proteins increases the positivity of this ELISA method, and that detection ofIgG, IgA, and IgM class anti-M2 to the four M2 proteins by immunoblotting is useful in diagnosing AMA-negative patients with PBC. (Internal Medicine 34: 496-501, 1995)
Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.
The mechanisms underlying isoniazid (INH)‐induced hepatitis were studied. INH‐induced hepatitis is known to occur due to the production of hepatotoxic metabolites in slow acetylators of INH, and hepatitis due to hypersensitivity reactions is also suspected to occur. The latter type of hepatitis was diagnosed by the presence of allergic reactions and a positive lymphocyte transformation test (LTT), while the former type was diagnosed by the absence of allergic symptoms and a negative LTT. Among 14 patients with INH‐induced hepatitis, nine had hepatitis due to abnormal metabolism of INH and five had hypersensitivity reactions. Comparison was made with a control group of 276 patients who had drug‐induced hepatic injury caused by hypersensitivity reactions to various other drugs. The metabolic group showed milder liver dysfunction than the control group. Hypersensitivity patients showed a disease state similar to the controls, and jaundice was more common in the hypersensitivity group than in the metabolic group. These findings suggest that there are two distinct disease states in patients with INH‐induced hepatitis, and that INH can cause mild liver damage due to abnormal handling of its metabolites or relatively severe hepatitis due to hypersensitivity reactions.
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