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. 1980 Mar;39(3):599–606.

Preciitating antibodies to mitochondrial antigens in patients with primary biliary cirrhosis.

K Miyachi, R C Gupta, E R Dickson, E M Tan
PMCID: PMC1538130  PMID: 6769623

Abstract

Sera of patients with primary biliary cirrhosis (PBC) were examined for the presence of precipitating antibodies to sonicated rat liver mitochondrial (M) fraction. Three distinct precipitating systems observed in double immunodiffusion were identified and called M-A, M-B and M-C. Unsonicated mitochondria did not form precipitin lines. Precipitating system M-A was found in nineteen of twenty (95 percent) sera from PBC. The mitochondrial antigen of M-A system had the unusual property of being resistant to enzymatic digestion with deoxyribonuclease (DNase), ribonuclease (RNase) and trypsin under standard conditions. The titres of antibody to M-A antigen correlated (P less than 0.05) with titres of mitochondrial immunofluorescence staining on unfixed mouse kidney sections. Precipitating systems M-B and M-C were present in seven of twenty ribonuclease and trypsin but resistant to ribonuclease indicating that it could be DNA-protein complex. The M-C antigen was destroyed by trypsin suggesting its protein character, but it was difficult to determine if nucleic acids might also be associated with antigenicity. The antibodies to mitochondrial antigens were not present in normals (fifteen health adults), systemic lupus erythematosus (forty patients), rheumatoid arthritis (fifteen patients) and chronic liver diseases (fifteen patients). The antibodies did not show identity with antibodies to ribosomal ribonucleo-protein and other known nuclear antigens previously reported. The data confirm previous reports concerning the heterogeneity of mitochondrial antibodies present in sera of patients with PBC. The antibody to M-A antigen appeared to be a diagnostically useful immunological marker since it was present in the majority of patients with PBC.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alspaugh M. A., Tan E. M. Antibodies to cellular antigens in Sjögren's syndrome. J Clin Invest. 1975 May;55(5):1067–1073. doi: 10.1172/JCI108007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. BAGGENSTOSS A. H., FOULK W. T., BUTT H. R., BAHN R. C. THE PATHOLOGY OF PRIMARY BILIARY CIRRHOSIS WITH EMPHASIS ON HISTOGENESIS. Am J Clin Pathol. 1964 Sep;42:259–276. doi: 10.1093/ajcp/42.3.259. [DOI] [PubMed] [Google Scholar]
  3. Ben-Yoseph Y., Shapira E., Doniach D. Further purification of the mitochondrial inner membrane autoantigen reacting with primary biliary cirrhosis sera. Immunology. 1974 Feb;26(2):311–321. [PMC free article] [PubMed] [Google Scholar]
  4. Berg P. A., Roitt I. M., Doniach D., Cooper H. M. Mitochondrial antibodies in primary biliary cirrhosis. IV. Significance of membrane structure for the complement-fixing antigen. Immunology. 1969 Aug;17(2):281–293. [PMC free article] [PubMed] [Google Scholar]
  5. Bianchi F. B., Penfold P. L., Roitt I. M. Mitochondrial antibodies in primary biliary cirrhosis. V. Ultrastructural localization of the antigen to the inner mitochondrial membrane using a direct peroxidase conjugate. Br J Exp Pathol. 1973 Dec;54(6):652–657. [PMC free article] [PubMed] [Google Scholar]
  6. Doniach D. Autoimmunity in liver diseases. Prog Clin Immunol. 1972;1:45–70. [PubMed] [Google Scholar]
  7. Doniach D., Delhanty J., Lindqvist H. J., Catterall R. D. Mitochondrial and other tissue autoantibodies in patients with biological false positive reactions for syphilis. Clin Exp Immunol. 1970 Jun;6(6):871–884. [PMC free article] [PubMed] [Google Scholar]
  8. Doniach D., Lindqvist H. L., Berg P. A. Non-organ-specific cytoplasmic antibodies detected by immunofluorescence. Int Arch Allergy Appl Immunol. 1971;41(4):501–513. doi: 10.1159/000230545. [DOI] [PubMed] [Google Scholar]
  9. Gupta R. C., Dickson E. R., McDuffie F. C., Baggenstoss A. H. Circulating IgG complexes in primary biliary cirrhosis. A serial study in forty patients followed for two years. Clin Exp Immunol. 1978 Oct;34(1):19–27. [PMC free article] [PubMed] [Google Scholar]
  10. Klatskin G., Kantor F. S. Mitochondrial antibody in primary biliary cirrhosis and other diseases. Ann Intern Med. 1972 Oct;77(4):533–541. doi: 10.7326/0003-4819-77-4-533. [DOI] [PubMed] [Google Scholar]
  11. Kurata N., Tan E. M. Identification of antibodies to nuclear acidic antigens by counterimmunoelectrophoresis. Arthritis Rheum. 1976 May-Jun;19(3):574–580. doi: 10.1002/art.1780190309. [DOI] [PubMed] [Google Scholar]
  12. LITTLEFIELD J. W., KELLER E. B., GROSS J., ZAMECNIK P. C. Studies on cytoplasmic ribonucleoprotein particles from the liver of the rat. J Biol Chem. 1955 Nov;217(1):111–123. [PubMed] [Google Scholar]
  13. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  14. Labro M. T., Andrieu M. C., Weber M., Homberg J. C. A new pattern of non-organ- and non-species-specific anti-organelle antibody detected by immunofluorescence: the mitochondrial antibody number 5. Clin Exp Immunol. 1978 Mar;31(3):357–366. [PMC free article] [PubMed] [Google Scholar]
  15. Miyachi K., Tan E. M. Antibodies reacting with ribosomal ribonucleoprotein in connective tissue diseases. Arthritis Rheum. 1979 Jan;22(1):87–93. doi: 10.1002/art.1780220114. [DOI] [PubMed] [Google Scholar]
  16. Picazo J. J., Tan E. M. Specificities of antibodies to native DNA. Scand J Rheumatol Suppl. 1975;11:35–41. doi: 10.3109/03009747509095627. [DOI] [PubMed] [Google Scholar]
  17. Sayers T. J., Binder T., Berg P. A. Heterogeneity of anti-mitochondrial antibodies: characterization and separation of the antigen associated with the pseudolupus erythematosus syndrome. Clin Exp Immunol. 1979 Jul;37(1):68–75. [PMC free article] [PubMed] [Google Scholar]
  18. Sharp G. C., Irvin W. S., Tan E. M., Gould R. G., Holman H. R. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med. 1972 Feb;52(2):148–159. doi: 10.1016/0002-9343(72)90064-2. [DOI] [PubMed] [Google Scholar]
  19. Sherlock S., Scheuer P. J. The presentation and diagnosis of 100 patients with primary biliary cirrhosis. N Engl J Med. 1973 Sep 27;289(13):674–678. doi: 10.1056/NEJM197309272891306. [DOI] [PubMed] [Google Scholar]
  20. Soloway R. D., Summerskill W. H., Baggenstoss A. H., Geall M. G., Gitnićk G. L., Elveback I. R., Schoenfield L. J. Clinical, biochemical, and histological remission of severe chronic active liver disease: a controlled study of treatments and early prognosis. Gastroenterology. 1972 Nov;63(5):820–833. [PubMed] [Google Scholar]
  21. Swana G. T., Swana M. R., Bottazzo G. F., Doniach D. A human-specific mitochondrial antibody its importance in the identification of organ-specific reactions. Clin Exp Immunol. 1977 Jun;28(3):517–525. [PMC free article] [PubMed] [Google Scholar]
  22. Tan E. M. An immunologic precipitin system between soluble nucleoprotein and serum antibody in systemic lupus erythematosus. J Clin Invest. 1967 May;46(5):735–745. doi: 10.1172/JCI105574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. WALKER J. G., DONIACH D., ROITT I. M., SHERLOCK S. SEROLOGICAL TESTS IN DIAGNOSIS OF PRIMARY BILIARY CIRRHOSIS. Lancet. 1965 Apr 17;1(7390):827–831. doi: 10.1016/s0140-6736(65)91372-3. [DOI] [PubMed] [Google Scholar]
  24. Wright D. J., Doniach D., Lessof M. H., Turk J. L., Grimble A. S., Catterall R. D. New antibody in early syphilis. Lancet. 1970 Apr 11;1(7650):740–743. doi: 10.1016/s0140-6736(70)90972-4. [DOI] [PubMed] [Google Scholar]

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