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. 1995 Oct;102(1):131–136. doi: 10.1111/j.1365-2249.1995.tb06646.x

Anti-M4 antibodies measured by a sulphite oxidase ELISA in patients with both anti-centromere and anti-M2 antibodies.

C C Bunn 1, M McMorrow 1
PMCID: PMC1553322  PMID: 7554379

Abstract

In this study the clinical features of patients with a serological overlap between scleroderma and primary biliary cirrhosis (PBC) were analysed. The entity was defined by the presence of both anti-centromere antibody (ACA) and anti-mitochondrial antibodies to the M2 antigen, pyruvate dehydrogenase. In addition the sera were assayed for anti-mitochondrial antibodies to the M4 antigen measured by an ELISA to sulphite oxidase (SO). First, anti-M2 was detected, not only in 58 out of 60 patients with PBC but also in eight out of 61 patients with ACA. These sera, together with sera from 53 normals and 99 from patients with various connective tissue diseases were then evaluated for anti-SO, which has been proposed by Klein and Berg to be a marker of progressive liver disease. Again, a high proportion (62%) of sera from patients with PBC were positive for anti-SO, and three of the eight patients who had ACA and anti-M2 also reacted with SO. We subsequently identified and included for study a further 10 patients positive for ACA and anti-M2, making a total of 18 patients with this profile. Features of limited cutaneous scleroderma were present in 94% and evidence of liver disease in 56%. Eight out of the 18 patients had anti-SO, and of these four had PBC, two had abnormal biochemical liver function tests but two had no evidence of liver disease. These data confirm that detection of anti-SO is limited to an anti-M2 subpopulation, and may be a marker for liver involvement with prognostic significance in scleroderma patients with ACA.

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Selected References

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  1. Alderuccio F., Toh B. H., Barnett A. J., Pedersen J. S. Identification and characterization of mitochondria autoantigens in progressive systemic sclerosis: identity with the 72,000 dalton autoantigen in primary biliary cirrhosis. J Immunol. 1986 Sep 15;137(6):1855–1859. [PubMed] [Google Scholar]
  2. Berg P. A., Klein R. Antimitochondrial antibodies in primary biliary cirrhosis and other disorders: definition and clinical relevance. Dig Dis. 1992;10(2):85–101. doi: 10.1159/000171347. [DOI] [PubMed] [Google Scholar]
  3. Berg P. A., Klein R. Clinical and prognostic relevance of different mitochondrial antibody profiles in primary biliary cirrhosis (PBC). Mol Aspects Med. 1985;8(3):235–247. doi: 10.1016/0098-2997(85)90008-1. [DOI] [PubMed] [Google Scholar]
  4. Bernstein R. M., Callender M. E., Neuberger J. M., Hughes G. R., Williams R. Anticentromere antibody in primary biliary cirrhosis. Ann Rheum Dis. 1982 Dec;41(6):612–614. doi: 10.1136/ard.41.6.612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Davis P. A., Leung P., Manns M., Kaplan M., Munoz S. J., Gorin F. A., Dickson E. R., Krawitt E., Coppel R., Gershwin M. E. M4 and M9 antibodies in the overlap syndrome of primary biliary cirrhosis and chronic active hepatitis: epitopes or epiphenomena? Hepatology. 1992 Nov;16(5):1128–1136. [PubMed] [Google Scholar]
  6. Dickson E. R., Grambsch P. M., Fleming T. R., Fisher L. D., Langworthy A. Prognosis in primary biliary cirrhosis: model for decision making. Hepatology. 1989 Jul;10(1):1–7. doi: 10.1002/hep.1840100102. [DOI] [PubMed] [Google Scholar]
  7. Fregeau D. R., Leung P. S., Coppel R. L., McNeilage L. J., Medsger T. A., Jr, Gershwin M. E. Autoantibodies to mitochondria in systemic sclerosis. Frequency and characterization using recombinant cloned autoantigen. Arthritis Rheum. 1988 Mar;31(3):386–392. doi: 10.1002/art.1780310310. [DOI] [PubMed] [Google Scholar]
  8. Fritzler M. J., Kinsella T. D. The CREST syndrome: a distinct serologic entity with anticentromere antibodies. Am J Med. 1980 Oct;69(4):520–526. doi: 10.1016/0002-9343(80)90462-3. [DOI] [PubMed] [Google Scholar]
  9. Fussey S. P., Guest J. R., James O. F., Bassendine M. F., Yeaman S. J. Identification and analysis of the major M2 autoantigens in primary biliary cirrhosis. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8654–8658. doi: 10.1073/pnas.85.22.8654. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Klein R., Berg P. A. Anti-M4 antibodies in primary biliary cirrhosis react with sulphite oxidase, an enzyme of the mitochondrial inter-membrane space. Clin Exp Immunol. 1991 Jun;84(3):445–448. [PMC free article] [PubMed] [Google Scholar]
  11. Klein R., Berg P. A. Anti-M9 antibodies in sera from patients with primary biliary cirrhosis recognize an epitope of glycogen phosphorylase. Clin Exp Immunol. 1990 Jul;81(1):65–71. doi: 10.1111/j.1365-2249.1990.tb05292.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Klein R., Berg P. A. Characterization of a new mitochondrial antigen-antibody system (M9/anti-M9) in patients with anti-M2 positive and anti-M2 negative primary biliary cirrhosis. Clin Exp Immunol. 1988 Oct;74(1):68–74. [PMC free article] [PubMed] [Google Scholar]
  13. Klein R., Huizenga J. R., Gips C. H., Berg P. A. Antimitochondrial antibody profiles in patients with primary biliary cirrhosis before orthotopic liver transplantation and titres of antimitochondrial antibody-subtypes after transplantation. J Hepatol. 1994 Feb;20(2):181–189. doi: 10.1016/s0168-8278(05)80056-x. [DOI] [PubMed] [Google Scholar]
  14. Klein R., Klöppel G., Garbe W., Fintelmann V., Berg P. A. Antimitochondrial antibody profiles determined at early stages of primary biliary cirrhosis differentiate between a benign and a progressive course of the disease. A retrospective analysis of 76 patients over 6-18 years. J Hepatol. 1991 Jan;12(1):21–27. doi: 10.1016/0168-8278(91)90903-o. [DOI] [PubMed] [Google Scholar]
  15. Ludwig J., Dickson E. R., McDonald G. S. Staging of chronic nonsuppurative destructive cholangitis (syndrome of primary biliary cirrhosis). Virchows Arch A Pathol Anat Histol. 1978 Aug 22;379(2):103–112. doi: 10.1007/BF00432479. [DOI] [PubMed] [Google Scholar]
  16. Makinen D., Fritzler M., Davis P., Sherlock S. Anticentromere antibodies in primary biliary cirrhosis. Arthritis Rheum. 1983 Jul;26(7):914–917. doi: 10.1002/art.1780260714. [DOI] [PubMed] [Google Scholar]
  17. McHugh N. J., James I. E., Fairburn K., Maddison P. J. Autoantibodies to mitochondrial and centromere antigens in primary biliary cirrhosis and systemic sclerosis. Clin Exp Immunol. 1990 Aug;81(2):244–249. doi: 10.1111/j.1365-2249.1990.tb03325.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moroi Y., Peebles C., Fritzler M. J., Steigerwald J., Tan E. M. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1627–1631. doi: 10.1073/pnas.77.3.1627. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Palmer J. M., Yeaman S. J., Bassendine M. F., James O. F. M4 and M9 autoantigens in primary biliary cirrhosis--a negative study. J Hepatol. 1993 Jun;18(2):251–254. doi: 10.1016/s0168-8278(05)80253-3. [DOI] [PubMed] [Google Scholar]
  20. Powell F. C., Schroeter A. L., Dickson E. R. Primary biliary cirrhosis and the CREST syndrome: a report of 22 cases. Q J Med. 1987 Jan;62(237):75–82. [PubMed] [Google Scholar]
  21. 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]
  22. Steen V. D., Ziegler G. L., Rodnan G. P., Medsger T. A., Jr Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum. 1984 Feb;27(2):125–131. doi: 10.1002/art.1780270202. [DOI] [PubMed] [Google Scholar]
  23. Surh C. D., Roche T. E., Danner D. J., Ansari A., Coppel R. L., Prindiville T., Dickson E. R., Gershwin M. E. Antimitochondrial autoantibodies in primary biliary cirrhosis recognize cross-reactive epitope(s) on protein X and dihydrolipoamide acetyltransferase of pyruvate dehydrogenase complex. Hepatology. 1989 Aug;10(2):127–133. doi: 10.1002/hep.1840100202. [DOI] [PubMed] [Google Scholar]
  24. Tan E. M., Rodnan G. P., Garcia I., Moroi Y., Fritzler M. J., Peebles C. Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. Arthritis Rheum. 1980 Jun;23(6):617–625. doi: 10.1002/art.1780230602. [DOI] [PubMed] [Google Scholar]
  25. Van de Water J., Cooper A., Surh C. D., Coppel R., Danner D., Ansari A., Dickson R., Gershwin M. E. Detection of autoantibodies to recombinant mitochondrial proteins in patients with primary biliary cirrhosis. N Engl J Med. 1989 May 25;320(21):1377–1380. doi: 10.1056/NEJM198905253202104. [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]
  27. Yeaman S. J., Fussey S. P., Danner D. J., James O. F., Mutimer D. J., Bassendine M. F. Primary biliary cirrhosis: identification of two major M2 mitochondrial autoantigens. Lancet. 1988 May 14;1(8594):1067–1070. doi: 10.1016/s0140-6736(88)91894-6. [DOI] [PubMed] [Google Scholar]

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