Two different subtypes of antimitochondrial antibodies are associated with primary biliary cirrhosis: Identification and characterization by radioimmunoassay and immunoblotting
✍ Scribed by Professor Dr. Michael Manns; Guido Gerken; Apostolos Kyriatsoulis; Christian Trautwein; Konrad Reske; Karl-Hermann Meyer Zum Büschenfelde
- Publisher
- John Wiley and Sons
- Year
- 1987
- Tongue
- English
- Weight
- 880 KB
- Volume
- 7
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
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 a t 48,000 daltons (p 48) on Western blot and from a patient with Stage 111 primary biliary cirrhosis reacting exclusively with a single 62,000 dalton polypeptide (p 62) were labeled with lZ5I; two radioimmunoassays 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 pseudolupus syndrome and 2 with syphilis 11, which were positive for antimitochondrial antibodies by immunofluorescence. Mitochondria1 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 cm3 and p 48 at 1.30 gm per cm3. Thus, radioimmunoassays 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.