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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1994 Jan;53(1):24–29. doi: 10.1136/ard.53.1.24

Anti-myeloperoxidase antibodies in patients with rheumatoid arthritis: prevalence, clinical correlates, and IgG subclass.

G Cambridge 1, M Williams 1, B Leaker 1, M Corbett 1, C R Smith 1
PMCID: PMC1005238  PMID: 8311550

Abstract

OBJECTIVES--To determine the prevalence and clinical associations of autoantibodies to myeloperoxidase (MPO) in an unselected series of well-characterised outpatients with rheumatoid arthritis (RA) and to compare the distribution of IgG subclasses of anti-MPO antibodies in these patients with that in patients with systemic vasculitis. PATIENTS AND METHODS--A study was made of 97 patients with RA, who have been seen regularly in this department for up to 20 years, and 29 patients with anti-neutrophil cytoplasmic antibody (ANCA) positive systemic vasculitis. Anti-MPO antibodies were detected using a direct-binding enzyme-linked immunosorbent assay (ELISA) with MPO from human granulocytes as antigen. The IgG subclass of anti-MPO antibodies was determined by ELISA using isotype specific monoclonal antibodies. RESULTS--Anti-MPO antibodies were detected in 12% of patients with RA. Six sera contained IgG anti-MPO antibodies only, 1 IgM only and 5 antibodies of both classes. In the patients with RA the predominant subclasses were IgG1 and IgG3: only 2 sera contained detectable IgG4 antibodies. This was in contrast to patients with vasculitis, in whom most sera contained IgG1, IgG3 and IgG4 anti-MPO antibodies. Anti-MPO antibodies in sera from both patient groups bound only to the native protein. None of the patients studied with RA had evidence of vasculitis affecting the nerves or kidney: three patients (1 positive for anti-MPO antibodies and 2 negative) had cutaneous vasculitis. In the patients with RA, positivity for anti-MPO antibodies was associated with nodules and number of active joints. Three patients with anti-MPO antibodies, and none without, had pulmonary fibrosis. CONCLUSIONS--Twelve per cent of a group of unselected outpatients with RA, but without evidence of major systemic vasculitis, had anti-MPO antibodies in their serum. Positivity for anti-MPO antibodies was more common in patients with nodular disease and lung involvement but not in patients with cutaneous vasculitis. IgG4 sub-class anti-MPO antibodies were present in 90% of sera from patients with ANCA-positive vasculitis and only 2/11 (18%) of anti-MPO antibody containing sera from patients with RA.

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Selected References

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  1. Aalberse R. C., van der Gaag R., van Leeuwen J. Serologic aspects of IgG4 antibodies. I. Prolonged immunization results in an IgG4-restricted response. J Immunol. 1983 Feb;130(2):722–726. [PubMed] [Google Scholar]
  2. Blanco F., Kalsi J., Ravirajan C. T., Speight P., Bradwell A. R., Isenberg D. A. IgG subclasses in systemic lupus erythematosus and other autoimmune rheumatic diseases. Lupus. 1992 Dec;1(6):391–399. doi: 10.1177/096120339200100609. [DOI] [PubMed] [Google Scholar]
  3. Brouwer E., Tervaert J. W., Horst G., Huitema M. G., van der Giessen M., Limburg P. C., Kallenberg C. G. Predominance of IgG1 and IgG4 subclasses of anti-neutrophil cytoplasmic autoantibodies (ANCA) in patients with Wegener's granulomatosis and clinically related disorders. Clin Exp Immunol. 1991 Mar;83(3):379–386. doi: 10.1111/j.1365-2249.1991.tb05647.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Conn D. L., McDuffie F. C., Holley K. E., Schroeter A. L. Immunologic mechanisms in systemic vasculitis. Mayo Clin Proc. 1976 Aug;51(8):511–518. [PubMed] [Google Scholar]
  5. Coremans I. E., Hagen E. C., Daha M. R., van der Woude F. J., van der Voort E. A., Kleijburg-van der Keur C., Breedveld F. C. Antilactoferrin antibodies in patients with rheumatoid arthritis are associated with vasculitis. Arthritis Rheum. 1992 Dec;35(12):1466–1475. doi: 10.1002/art.1780351210. [DOI] [PubMed] [Google Scholar]
  6. Devey M. E., Lee S. R., Le Page S., Feldman R., Isenberg D. A. Serial studies of the IgG subclass and functional affinity of DNA antibodies in systemic lupus erythematosus. J Autoimmun. 1988 Oct;1(5):483–494. doi: 10.1016/0896-8411(88)90069-8. [DOI] [PubMed] [Google Scholar]
  7. Esnault V. L., Jayne D. R., Weetman A. P., Lockwood C. M. IgG subclass distribution and relative functional affinity of anti-myeloperoxidase antibodies in systemic vasculitis at presentation and during follow-up. Immunology. 1991 Dec;74(4):714–718. [PMC free article] [PubMed] [Google Scholar]
  8. Falk R. J., Becker M., Terrell R., Jennette J. C. Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase. Clin Exp Immunol. 1992 Aug;89(2):274–278. doi: 10.1111/j.1365-2249.1992.tb06944.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fleming A., Crown J. M., Corbett M. Prognostic value of early features in rheumatoid disease. Br Med J. 1976 May 22;1(6020):1243–1245. doi: 10.1136/bmj.1.6020.1243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fleming A., Dodman S., Crown J. M., Corbett M. Extra-articular features in early rheumatoid disease. Br Med J. 1976 May 22;1(6020):1241–1243. doi: 10.1136/bmj.1.6020.1241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hagen E. C., Ballieux B. E., van Es L. A., Daha M. R., van der Woude F. J. Antineutrophil cytoplasmic autoantibodies: a review of the antigens involved, the assays, and the clinical and possible pathogenetic consequences. Blood. 1993 Apr 15;81(8):1996–2002. [PubMed] [Google Scholar]
  12. Kacaki J. N., Callerame M. L., Blomgren S. E., Vaughan J. H. Immunoglobulin G subclasses of antinuclear antibodies and renal deposits. Comparison of systemic lupus erythematosus, drug-induced lupus and rheumatoid arthritis. Arthritis Rheum. 1971 Mar-Apr;14(2):276–282. doi: 10.1002/art.1780140214. [DOI] [PubMed] [Google Scholar]
  13. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  14. Lassoued S., Sixou L., Oksman F., Pages M., Fournie A. Antineutrophil cytoplasmic antibodies and antibodies to myeloperoxidase in rheumatoid arthritis. Arthritis Rheum. 1991 Aug;34(8):1069–1070. doi: 10.1002/art.1780340821. [DOI] [PubMed] [Google Scholar]
  15. Lesavre P. Antineutrophil cytoplasmic autoantibodies antigen specificity. Am J Kidney Dis. 1991 Aug;18(2):159–163. doi: 10.1016/s0272-6386(12)80873-0. [DOI] [PubMed] [Google Scholar]
  16. Moodie F. D., Leaker B., Cambridge G., Totty N. F., Segal A. W. Alpha-enolase: a novel cytosolic autoantigen in ANCA positive vasculitis. Kidney Int. 1993 Mar;43(3):675–681. doi: 10.1038/ki.1993.97. [DOI] [PubMed] [Google Scholar]
  17. Nada A. K., Torres V. E., Ryu J. H., Lie J. T., Holley K. E. Pulmonary fibrosis as an unusual clinical manifestation of a pulmonary-renal vasculitis in elderly patients. Mayo Clin Proc. 1990 Jun;65(6):847–856. doi: 10.1016/s0025-6196(12)62575-0. [DOI] [PubMed] [Google Scholar]
  18. Nässberger L., Sjöholm A. G., Sturfelt G. Absence of circulating antineutrophil cytoplasm antibodies (ANCA) in severe vasculitis associated with rheumatoid arthritis. Scand J Rheumatol. 1990;19(3):189–192. doi: 10.3109/03009749009095042. [DOI] [PubMed] [Google Scholar]
  19. Roberts D. E., Peebles C., Curd J. G., Tan E. M., Rubin R. L. Autoantibodies to native myeloperoxidase in patients with pulmonary hemorrhage and acute renal failure. J Clin Immunol. 1991 Nov;11(6):389–397. doi: 10.1007/BF00918805. [DOI] [PubMed] [Google Scholar]
  20. Savige J. A., Gallicchio M. C., Stockman A., Cunningham T. J., Rowley M. J., Georgiou T., Davies D. Anti-neutrophil cytoplasm antibodies in rheumatoid arthritis. Clin Exp Immunol. 1991 Oct;86(1):92–98. doi: 10.1111/j.1365-2249.1991.tb05779.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Schur P. H. IgG subclasses--a review. Ann Allergy. 1987 Feb;58(2):89-96, 99. [PubMed] [Google Scholar]
  22. Tervaert J. W., Goldschmeding R., Elema J. D., Limburg P. C., van der Giessen M., Huitema M. G., Koolen M. I., Hené R. J., The T. H., van der Hem G. K. Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum. 1990 Aug;33(8):1264–1272. doi: 10.1002/art.1780330829. [DOI] [PubMed] [Google Scholar]

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