Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1967 Aug 1;126(2):277–290. doi: 10.1084/jem.126.2.277

MITOCHONDRIAL ANTIBODIES IN PRIMARY BILIARY CIRRHOSIS

I. LOCALIZATION OF THE ANTIGEN TO MITOCHONDRIAL MEMBRANES

Peter A Berg 1, Deborah Doniach 1, Ivan M Roitt 1
PMCID: PMC2138313  PMID: 4165742

Abstract

The antigen reacting with complement-fixing antibodies in the sera of patients with primary biliary cirrhosis was localized predominantly in the mitochondrial fraction of tissue homogenates obtained by differential centrifugation. Purified mitochondrial preparations had a high content of the antigen whereas purified lysosomes failed to fix complement with PBC sera. Analysis of a number of fractionation experiments showed a high correlation between antigen content and the mitochondrial enzyme succinic dehydrogenase in all fractions. There was much poorer correlation with lysosomal and micrososomal enzyme markers. The patterns of staining obtained with a fluorescein conjugate of IgG from a PBC patient closely paralleled those obtained with a histochemical method for the demonstration of succinic dehydrogenase, further confirming the mitochondrial localization of the antigen. Staining was brightest in cells containing mitochondria with well-developed cristae. Studies on mitochondria fragmented by osmotic lysis, hexane, lysolecithin, and ultrasound suggest that the antigen is associated with the mitochondrial inner membranes.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. ASHERSON G. L. Antibodies against nuclear and cytoplasmic cell constituents in systemic lupus erythematosus and other diseases. Br J Exp Pathol. 1959 Jun;40(3):209–215. [PMC free article] [PubMed] [Google Scholar]
  2. BAUR S., ROITT I. M., DONIACH D. CHARACTERIZATION OF THE HUMAN GASTRIC PARIETAL CELL AUTO-ANTIGEN. Immunology. 1965 Jan;8:62–68. [PMC free article] [PubMed] [Google Scholar]
  3. Beaufay H., Jacques P., Baudhuin P., Sellinger O. Z., Berthet J., De Duve C. Tissue fractionation studies. 18. Resolution of mitochondrial fractions from rat liver into three distinct populations of cytoplasmic particles by means of density equilibration in various gradients. Biochem J. 1964 Jul;92(1):184–205. doi: 10.1042/bj0920184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. DE DUVE C., PRESSMAN B. C., GIANETTO R., WATTIAUX R., APPELMANS F. Tissue fractionation studies. 6. Intracellular distribution patterns of enzymes in rat-liver tissue. Biochem J. 1955 Aug;60(4):604–617. doi: 10.1042/bj0600604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. DEICHER H. R., HOLMAN H. R., KUNKEL H. G. Anti-cytoplasmic factors in the sera of patients with systemic lupus erythematosus and certain other diseases. Arthritis Rheum. 1960 Feb;3:1–15. doi: 10.1002/art.1780030102. [DOI] [PubMed] [Google Scholar]
  6. Doniach D., Roitt I. M., Walker J. G., Sherlock S. Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications. Clin Exp Immunol. 1966 Jul;1(3):237–262. [PMC free article] [PubMed] [Google Scholar]
  7. FABER V., IVERSEN K., NORUP G., ELLING P., POULSEN H. SEROLOGY IN HEPATIC CIRRHOSIS. Tijdschr Gastroenterol. 1964;7:245–252. doi: 10.1159/000387708. [DOI] [PubMed] [Google Scholar]
  8. Goudie R. B., Macsween R. N., Goldberg D. M. Serological and histological diagnosis of primary biliary cirrhosis. J Clin Pathol. 1966 Nov;19(6):527–538. doi: 10.1136/jcp.19.6.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kaplan M. H. Autoantibodies to heart and rheumatic fever: the induction of autoimmunity to heart by streptococcal antigen cross-reactive with heart. Ann N Y Acad Sci. 1965 Jun 30;124(2):904–915. doi: 10.1111/j.1749-6632.1965.tb19014.x. [DOI] [PubMed] [Google Scholar]
  10. Klion F. M., Schaffner F. Electron microscopic observations in primary biliary cirrhosis. Arch Pathol. 1966 Feb;81(2):152–161. [PubMed] [Google Scholar]
  11. 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]
  12. Lagercrantz R., Hammarström S., Perlmann P., Gustafsson B. E. Immunological studies in ulcerative colitis. 3. Incidence of antibodies to colon-antigen in ulcerative colitis and other gastro-intestinal diseases. Clin Exp Immunol. 1966 Jul;1(3):263–276. [PMC free article] [PubMed] [Google Scholar]
  13. MACKAY I. R., LARKIN L. The significance of the presence in human serum of complement-fixing antibodies to human tissue antigens. Australas Ann Med. 1958 Aug;7(3):251–258. doi: 10.1111/imj.1958.7.3.251. [DOI] [PubMed] [Google Scholar]
  14. MARKOWITZ A. S., LANGE C. F., Jr STREPTOCOCCAL RELATED GLOMERULONEPHRITIS. I. ISOLATION, IMMUNOCHEMISTRY AND COMPARATIVE CHEMISTRY OF SOLUBLE FRACTIONS FROM TYPE 12 NEPHRITOGENIC STREPTOCOCCI AND HUMAN GLOMERULI. J Immunol. 1964 Apr;92:565–575. [PubMed] [Google Scholar]
  15. NACHLAS M. M., TSOU K. C., DE SOUZA E., CHENG C. S., SELIGMAN A. M. Cytochemical demonstration of succinic dehydrogenase by the use of a new p-nitrophenyl substituted ditetrazole. J Histochem Cytochem. 1957 Jul;5(4):420–436. doi: 10.1177/5.4.420. [DOI] [PubMed] [Google Scholar]
  16. OGAWA K., BARRNETT R. J. ELECTRON HISTOCHEMICAL EXAMINATION OF OXIDATIVE ENZYMES AND MITOCHONDRIA. Nature. 1964 Aug 15;203:724–726. doi: 10.1038/203724a0. [DOI] [PubMed] [Google Scholar]
  17. PARONETTO F., SCHAFFNER F., MUTTER R. D., KNIFFEN J. C., POPPER H. CIRCULATING ANTIBODIES TO BILE DUCTULAR CELLS IN VARIOUS LIVER DISEASES. JAMA. 1964 Feb 15;187:503–506. doi: 10.1001/jama.1964.03060200035006. [DOI] [PubMed] [Google Scholar]
  18. PARONETTO F., SCHAFFNER F., POPPER H. IMMUNOCYTOCHEMICAL AND SEROLOGIC OBSERVATIONS IN PRIMARY BILIARY CIRRHOSIS. N Engl J Med. 1964 Nov 26;271:1123–1128. doi: 10.1056/NEJM196411262712201. [DOI] [PubMed] [Google Scholar]
  19. RAPPORT M. M., GRAF L. Immunochemical analysis based on complement fixation. Ann N Y Acad Sci. 1957 Dec 16;69(4):608–632. doi: 10.1111/j.1749-6632.1957.tb49700.x. [DOI] [PubMed] [Google Scholar]
  20. ROITT I. M., LING N. R., DONIACH D., COUCHMAN K. G. THE CYTOPLASMIC AUTO-ANTIGEN OF THE HUMAN THYROID. I. IMMUNOLOGICAL AND BIOCHEMICAL CHARACTERISTICS. Immunology. 1964 Jul;7:375–393. [PMC free article] [PubMed] [Google Scholar]
  21. RUBIN E., SCHAFFNER F., POPPER H. Localization of the basic injury in primary biliary cirrhosis. JAMA. 1963 Feb 2;183:331–334. doi: 10.1001/jama.1963.63700050001013. [DOI] [PubMed] [Google Scholar]
  22. Rümke P. Anticytoplasmic auto-antibodies in a patient with signs of tumour resistance. Eur J Cancer. 1965 Nov;1(3):321–325. doi: 10.1016/0014-2964(65)90070-8. [DOI] [PubMed] [Google Scholar]
  23. SLATER T. F., PLANTEROSE D. N. An assay procedure for a succinate-neotetrazolium-reductase system. Biochem J. 1960 Mar;74:591–596. doi: 10.1042/bj0740591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Seligman A. M., Ueno H., Morizono Y., Wasserkrug H. L., Katzoff L., Hanker J. S. Electron microscopic demonstration of dehydrogenase activity with a new osmiophilic ditetrazolium salt (TC-NBT). J Histochem Cytochem. 1967 Jan;15(1):1–13. doi: 10.1177/15.1.1. [DOI] [PubMed] [Google Scholar]
  25. Sherlock S. Biliary secretory failure in man. The problem of cholestasis. Ann Intern Med. 1966 Sep;65(3):397–408. doi: 10.7326/0003-4819-65-3-397. [DOI] [PubMed] [Google Scholar]
  26. 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]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES