Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Aug;89(2):274–278. doi: 10.1111/j.1365-2249.1992.tb06944.x

Anti-myeloperoxidase autoantibodies react with native but not denatured myeloperoxidase.

R J Falk 1, M Becker 1, R Terrell 1, J C Jennette 1
PMCID: PMC1554440  PMID: 1379133

Abstract

We wondered whether anti-myeloperoxidase (MPO) autoantibodies (MPO-ANCA) found in patients with systemic vasculitis react with a conformational epitope or epitopes on the MPO molecule. Sera from 15 human MPO-ANCA, and a polyclonal and a monoclonal anti-MPO antibodies were reacted with MPO in native and denatured states. Human MPO-ANCA and mouse monoclonal anti-MPO reacted with native MPO, and a 120-kD band representing the MPO hologenzyme, but not with denatured MPO fragments; however, MPO-ANCA and mouse anti-MPO did not demonstrate competitive inhibition of binding to MPO. Polyclonal rabbit anti-MPO reacted with both native and denatured MPO. All MPO-ANCA tested showed the same patterns of reactivity with native and denatured MPO in dot blot and Western blot analyses. Both polyclonal and monoclonal anti-MPO antibodies inhibited MPO's protein iodination by over 90%, whereas MPO-ANCA IgGs, normal IgGs and disease control IgGs did not. These data suggest that (i) MPO-ANCA interact with a conformational epitope on the MPO molecule; and (ii) MPO-ANCA from different patients have similar reactivity with native versus denatured MPO.

Full text

PDF
274

Images in this article

275Fig. 1
on p.275
276Fig. 2
on p.276
276Fig. 3
on p.276
276Fig. 4
on p.276

Selected References

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

  1. Andrews P. C., Krinsky N. I. The reductive cleavage of myeloperoxidase in half, producing enzymically active hemi-myeloperoxidase. J Biol Chem. 1981 May 10;256(9):4211–4218. [PubMed] [Google Scholar]
  2. Benjamin D. C., Berzofsky J. A., East I. J., Gurd F. R., Hannum C., Leach S. J., Margoliash E., Michael J. G., Miller A., Prager E. M. The antigenic structure of proteins: a reappraisal. Annu Rev Immunol. 1984;2:67–101. doi: 10.1146/annurev.iy.02.040184.000435. [DOI] [PubMed] [Google Scholar]
  3. Charles L. A., Falk R. J., Jennette J. C. Reactivity of anti-neutrophil cytoplasmic autoantibodies with HL-60 cells. Clin Immunol Immunopathol. 1989 Nov;53(2 Pt 1):243–253. doi: 10.1016/0090-1229(89)90054-8. [DOI] [PubMed] [Google Scholar]
  4. Falk R. J. ANCA-associated renal disease. Kidney Int. 1990 Nov;38(5):998–1010. doi: 10.1038/ki.1990.304. [DOI] [PubMed] [Google Scholar]
  5. Falk R. J., Hogan S., Carey T. S., Jennette J. C. Clinical course of anti-neutrophil cytoplasmic autoantibody-associated glomerulonephritis and systemic vasculitis. The Glomerular Disease Collaborative Network. Ann Intern Med. 1990 Nov 1;113(9):656–663. doi: 10.7326/0003-4819-113-9-656. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. 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]
  8. Finn A. L., Tsai L. M., Falk R. J. Monoclonal antibodies to the apical chloride channel in Necturus gallbladder inhibit the chloride conductance. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7649–7652. doi: 10.1073/pnas.86.19.7649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Jandl R. C., André-Schwartz J., Borges-DuBois L., Kipnes R. S., McMurrich B. J., Babior B. M. Termination of the respiratory burst in human neutrophils. J Clin Invest. 1978 May;61(5):1176–1185. doi: 10.1172/JCI109033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jenne D. E., Tschopp J., Lüdemann J., Utecht B., Gross W. L. Wegener's autoantigen decoded. Nature. 1990 Aug 9;346(6284):520–520. doi: 10.1038/346520a0. [DOI] [PubMed] [Google Scholar]
  12. Jennette J. C., Falk R. J. Antineutrophil cytoplasmic autoantibodies and associated diseases: a review. Am J Kidney Dis. 1990 Jun;15(6):517–529. doi: 10.1016/s0272-6386(12)80521-x. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. 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]
  15. Klebanoff S. J., Clark R. A. Iodination by human polymorphonuclear leukocytes: a re-evaluation. J Lab Clin Med. 1977 Mar;89(3):675–686. [PubMed] [Google Scholar]
  16. Laver W. G., Air G. M., Webster R. G., Smith-Gill S. J. Epitopes on protein antigens: misconceptions and realities. Cell. 1990 May 18;61(4):553–556. doi: 10.1016/0092-8674(90)90464-p. [DOI] [PubMed] [Google Scholar]
  17. Lüdemann J., Utecht B., Gross W. L. Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme. J Exp Med. 1990 Jan 1;171(1):357–362. doi: 10.1084/jem.171.1.357. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matheson N. R., Wong P. S., Travis J. Isolation and properties of human neutrophil myeloperoxidase. Biochemistry. 1981 Jan 20;20(2):325–330. doi: 10.1021/bi00505a015. [DOI] [PubMed] [Google Scholar]
  19. Nauseef W. M., Malech H. L. Analysis of the peptide subunits of human neutrophil myeloperoxidase. Blood. 1986 May;67(5):1504–1507. [PubMed] [Google Scholar]
  20. 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]
  21. 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]
  22. Root R. K., Stossel T. P. Myeloperoxidase-mediated iodination by granulocytes. Intracellular site of operation and some regulating factors. J Clin Invest. 1974 May;53(5):1207–1215. doi: 10.1172/JCI107667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]
  24. 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]
  25. 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]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES