Abstract
Vasculitis associated anticytoplasmic autoantibodies (ANCA) are directed against enzymes in the granules of both neutrophils and monocytes. These autoantibodies can be detected by indirect immunofluorescence technique (IIFT) using ethanol-fixed cytospins. We here report the identification of a novel specificity of autoantibodies, present in the sera of eight patients, that reacted only with eosinophils in the IIFT. By immunoprecipitation and ELISA experiments it was shown that the autoantibodies in these sera were directed against eosinophil peroxidase (EPO). There was no apparent influence on initial substrate conversion rate, but reduced plateau levels suggested increased inactivation of the enzyme in the course of the peroxidase reaction. Flow cytometry studies demonstrated the presence of EPO on the surface of primed eosinophils. Anti-EPO sera and purified anti-EPO immunoglobulins significantly increased the release of reactive oxygen species from primed eosinophils. The patients with anti-EPO antibodies suffered from clinically diverse disorders, with more or less generalized manifestations involving the kidneys, blood vessels, lungs and/or joints.
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- Bakkenist A. R., Wever R., Vulsma T., Plat H., van Gelder B. F. Isolation procedure and some properties of myeloperoxidase from human leucocytes. Biochim Biophys Acta. 1978 May 11;524(1):45–54. doi: 10.1016/0005-2744(78)90101-8. [DOI] [PubMed] [Google Scholar]
- Bolscher B. G., Plat H., Wever R. Some properties of human eosinophil peroxidase, a comparison with other peroxidases. Biochim Biophys Acta. 1984 Jan 31;784(2-3):177–186. doi: 10.1016/0167-4838(84)90125-0. [DOI] [PubMed] [Google Scholar]
- Duerr R. H., Targan S. R., Landers C. J., LaRusso N. F., Lindsay K. L., Wiesner R. H., Shanahan F. Neutrophil cytoplasmic antibodies: a link between primary sclerosing cholangitis and ulcerative colitis. Gastroenterology. 1991 May;100(5 Pt 1):1385–1391. [PubMed] [Google Scholar]
- Falk R. J., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic vasculitis and idiopathic necrotizing and crescentic glomerulonephritis. N Engl J Med. 1988 Jun 23;318(25):1651–1657. doi: 10.1056/NEJM198806233182504. [DOI] [PubMed] [Google Scholar]
- Falk R. J., Terrell R. S., Charles L. A., Jennette J. C. Anti-neutrophil cytoplasmic autoantibodies induce neutrophils to degranulate and produce oxygen radicals in vitro. Proc Natl Acad Sci U S A. 1990 Jun;87(11):4115–4119. doi: 10.1073/pnas.87.11.4115. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gleich G. J., Adolphson C. R. The eosinophilic leukocyte: structure and function. Adv Immunol. 1986;39:177–253. doi: 10.1016/s0065-2776(08)60351-x. [DOI] [PubMed] [Google Scholar]
- Goldschmeding R., van der Schoot C. E., ten Bokkel Huinink D., Hack C. E., van den Ende M. E., Kallenberg C. G., von dem Borne A. E. Wegener's granulomatosis autoantibodies identify a novel diisopropylfluorophosphate-binding protein in the lysosomes of normal human neutrophils. J Clin Invest. 1989 Nov;84(5):1577–1587. doi: 10.1172/JCI114335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Henderson W. R., Chi E. Y., Klebanoff S. J. Eosinophil peroxidase-induced mast cell secretion. J Exp Med. 1980 Aug 1;152(2):265–279. doi: 10.1084/jem.152.2.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jennette J. C., Hoidal J. R., Falk R. J. Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. Blood. 1990 Jun 1;75(11):2263–2264. [PubMed] [Google Scholar]
- Jennette J. C., Wilkman A. S., Falk R. J. Anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and vasculitis. Am J Pathol. 1989 Nov;135(5):921–930. [PMC free article] [PubMed] [Google Scholar]
- Jong E. C., Klebanoff S. J. Eosinophil-mediated mammalian tumor cell cytotoxicity: role of the peroxidase system. J Immunol. 1980 Apr;124(4):1949–1953. [PubMed] [Google Scholar]
- Jong E. C., Mahmoud A. A., Klebanoff S. J. Peroxidase-mediated toxicity to schistosomula of Schistosoma mansoni. J Immunol. 1981 Feb;126(2):468–471. [PubMed] [Google Scholar]
- Kallenberg C. G., Tervaert J. W., van der Woude F. J., Goldschmeding R., von dem Borne A. E., Weening J. J. Autoimmunity to lysosomal enzymes: new clues to vasculitis and glomerulonephritis? Immunol Today. 1991 Feb;12(2):61–64. doi: 10.1016/0167-5699(91)90159-q. [DOI] [PubMed] [Google Scholar]
- Kay A. B. Eosinophils as effector cells in immunity and hypersensitivity disorders. Clin Exp Immunol. 1985 Oct;62(1):1–12. [PMC free article] [PubMed] [Google Scholar]
- Klaassen R. J., Goldschmeding R., Dolman K. M., Vlekke A. B., Weigel H. M., Eeftinck Schattenkerk J. K., Mulder J. W., Westedt M. L., von dem Borne A. E. Anti-neutrophil cytoplasmic autoantibodies in patients with symptomatic HIV infection. Clin Exp Immunol. 1992 Jan;87(1):24–30. doi: 10.1111/j.1365-2249.1992.tb06408.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koenderman L., Kok P. T., Hamelink M. L., Verhoeven A. J., Bruijnzeel P. L. An improved method for the isolation of eosinophilic granulocytes from peripheral blood of normal individuals. J Leukoc Biol. 1988 Aug;44(2):79–86. doi: 10.1002/jlb.44.2.79. [DOI] [PubMed] [Google Scholar]
- Mayet W. J., Hermann E., Finsterwalder J., Rieder H., Poralla T., Meyer Zum Büschenfelde K. H. Antibodies to cathepsin G in Crohn's disease. Eur J Clin Invest. 1992 Jun;22(6):427–433. doi: 10.1111/j.1365-2362.1992.tb01485.x. [DOI] [PubMed] [Google Scholar]
- Niles J. L., McCluskey R. T., Ahmad M. F., Arnaout M. A. Wegener's granulomatosis autoantigen is a novel neutrophil serine proteinase. Blood. 1989 Nov 1;74(6):1888–1893. [PubMed] [Google Scholar]
- Nässberger L., Jonsson H., Sjöholm A. G., Sturfelt G., Heubner A. Circulating anti-elastase in systemic lupus erythematosus. Lancet. 1989 Mar 4;1(8636):509–509. doi: 10.1016/s0140-6736(89)91420-7. [DOI] [PubMed] [Google Scholar]
- Nölle B., Specks U., Lüdemann J., Rohrbach M. S., DeRemee R. A., Gross W. L. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med. 1989 Jul 1;111(1):28–40. doi: 10.7326/0003-4819-111-1-28. [DOI] [PubMed] [Google Scholar]
- Pulford K. A., Erber W. N., Crick J. A., Olsson I., Micklem K. J., Gatter K. C., Mason D. Y. Use of monoclonal antibody against human neutrophil elastase in normal and leukaemic myeloid cells. J Clin Pathol. 1988 Aug;41(8):853–860. doi: 10.1136/jcp.41.8.853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Roos D., de Boer M., Borregard N., Bjerrum O. W., Valerius N. H., Seger R. A., Mühlebach T., Belohradsky B. H., Weening R. S. Chronic granulomatous disease with partial deficiency of cytochrome b558 and incomplete respiratory burst: variants of the X-linked, cytochrome b558-negative form of the disease. J Leukoc Biol. 1992 Feb;51(2):164–171. doi: 10.1002/jlb.51.2.164. [DOI] [PubMed] [Google Scholar]
- Skubitz K. M., Christiansen N. P., Mendiola J. R. Preparation and characterization of monoclonal antibodies to human neutrophil cathepsin G, lactoferrin, eosinophil peroxidase, and eosinophil major basic protein. J Leukoc Biol. 1989 Aug;46(2):109–118. doi: 10.1002/jlb.46.2.109. [DOI] [PubMed] [Google Scholar]
- Snook J. A., Chapman R. W., Fleming K., Jewell D. P. Anti-neutrophil nuclear antibody in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis. Clin Exp Immunol. 1989 Apr;76(1):30–33. [PMC free article] [PubMed] [Google Scholar]
- 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]
- Tervaert J. W., Goldschmeding R., Elema J. D., van der Giessen M., Huitema M. G., van der Hem G. K., The T. H., von dem Borne A. E., Kallenberg C. G. Autoantibodies against myeloid lysosomal enzymes in crescentic glomerulonephritis. Kidney Int. 1990 Feb;37(2):799–806. doi: 10.1038/ki.1990.48. [DOI] [PubMed] [Google Scholar]
- Tervaert J. W., Huitema M. G., Hené R. J., Sluiter W. J., The T. H., van der Hem G. K., Kallenberg C. G. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet. 1990 Sep 22;336(8717):709–711. doi: 10.1016/0140-6736(90)92205-v. [DOI] [PubMed] [Google Scholar]
- Tervaert J. W., van der Woude F. J., Fauci A. S., Ambrus J. L., Velosa J., Keane W. F., Meijer S., van der Giessen M., van der Hem G. K., The T. H. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med. 1989 Nov;149(11):2461–2465. doi: 10.1001/archinte.149.11.2461. [DOI] [PubMed] [Google Scholar]
- Thompson R. A., Lee S. S. Antineutrophil cytoplasmic antibodies. Lancet. 1989 Mar 25;1(8639):670–671. doi: 10.1016/s0140-6736(89)92172-7. [DOI] [PubMed] [Google Scholar]
- Wever R., Plat H., Hamers M. N. Human eosinophil peroxidase: a novel isolation procedure, spectral properties and chlorinating activity. FEBS Lett. 1981 Jan 26;123(2):327–331. doi: 10.1016/0014-5793(81)80320-1. [DOI] [PubMed] [Google Scholar]
- Wiik A. The value of specific ANA determination in rheumatology. Update 1986. Allergy. 1987 May;42(4):241–261. doi: 10.1111/j.1398-9995.1987.tb02207.x. [DOI] [PubMed] [Google Scholar]
- van de Wiel B. A., Dolman K. M., van der Meer-Gerritsen C. H., Hack C. E., von dem Borne A. E., Goldschmeding R. Interference of Wegener's granulomatosis autoantibodies with neutrophil Proteinase 3 activity. Clin Exp Immunol. 1992 Dec;90(3):409–414. doi: 10.1111/j.1365-2249.1992.tb05860.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- van der Schoot C. E., von dem Borne A. E., Tetteroo P. A. Characterization of myeloid leukemia by monoclonal antibodies, with an emphasis on antibodies against myeloperoxidase. Acta Haematol. 1987;78 (Suppl 1):32–40. doi: 10.1159/000205900. [DOI] [PubMed] [Google Scholar]
- van der Woude F. J., Rasmussen N., Lobatto S., Wiik A., Permin H., van Es L. A., van der Giessen M., van der Hem G. K., The T. H. Autoantibodies against neutrophils and monocytes: tool for diagnosis and marker of disease activity in Wegener's granulomatosis. Lancet. 1985 Feb 23;1(8426):425–429. doi: 10.1016/s0140-6736(85)91147-x. [DOI] [PubMed] [Google Scholar]