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Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: Identification and characterization by radioimmunoassay and immunoblotting
Author(s) -
Manns Michael,
Gerken Guido,
Kyriatsoulis Apostolos,
Trautwein Christian,
Reske Konrad,
Zum Büschenfelde KarlHermann Meyer
Publication year - 1987
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840070517
Subject(s) - primary biliary cirrhosis , antibody , medicine , biliary cirrhosis , radioimmunoassay , pathology , cirrhosis , anti nuclear antibody , microbiology and biotechnology , immunology , gastroenterology , autoimmune disease , autoantibody , biology
Antimitochondrial antibodies from patients with primary biliary cirrhosis react with different mitochondrial polypeptides as demonstrated by Western blots. The IgG fractions of a patient with primary biliary cirrhosis Stage I reacting exclusively with a pair of polypeptides at 48,000 daltons (p 48) on Western blot and from a patient with Stage III primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with 125 I; two radio‐immunoassays were established detecting antimitochondrial antibodies against p 62 and p 48, respectively. Autologous sera blocked the assay, but the two reference sera did not block each other. Fourteen of 40 patients with primary biliary cirrhosis reacted with p 62, 6/40 with p 48 and 20 sera with both antigens. Sera from 200 patients with various hepatic and nonhepatic diseases were negative for anti‐p 62 and anti‐p 48. This collection of sera included 5 patients with nonhepatic autoimmune disorders, 3 with drug‐induced pseudo‐lupus syndrome and 2 with syphilis II, which were positive for antimitochondrial antibodies by immunofluo‐rescence. Mitochondrial autoantigens p 62 and p 48 were both localized on mitoplasts, presumably inner mitochondrial membranes; they were thermolabile, trypsin‐ and chymotrypsin‐sensitive, but resistant to DNAase, RNAase and neuraminidase treatments. In cesium chloride density gradients, p 62 floated at 1.28 gm per cm 3 and p 48 at 1.30 gm per cm 3 . Thus, radio‐immunoassays have been developed that specifically detect two distinct primary biliary cirrhosis‐specific subtypes of antimitochondrial antibodies: anti‐p 62 and anti‐p 48. All primary biliary cirrhosis sera were positive for at least one of these antimitochondrial antibodies subtypes. The reaction of antimitochondrial antibodies with mitochondrial antigens p 62 and p 48 is due to different autoantibody subtypes and not due to identical determinants on different polypeptides.