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. 1997 Jan;40(1):102–104. doi: 10.1136/gut.40.1.102

Lack of effect of antineutrophil cytoplasmic antibodies associated with ulcerative colitis on superoxide anion production from neutrophils.

P Gionchetti 1, M Vecchi 1, F Rizzello 1, M Ferretti 1, C Calabresi 1, A Venturi 1, M B Bianchi 1, C Brignola 1, R A Sinico 1, R De Franchis 1, M Miglioli 1, M Campieri 1
PMCID: PMC1027016  PMID: 9155584

Abstract

BACKGROUND: Antineutrophil cytoplasmic antibodies (ANCAs) from patients with vasculitidis can induce neutrophils to release oxygen radicals in vitro. ANCAs with a perinuclear pattern of immunofluorescence are found in most patients with ulcerative colitis, but several findings are against ANCAs having a pathogenetic role in this disease. AIMS: To evaluate the influence of ANCAs associated with ulcerative colitis on the respiratory burst activity of neutrophils. PATIENTS: Serum samples were obtained from 14 patients with ulcerative colitis, seven of whom showed positivity for p-ANCAs, three patients with vasculitidis, two with positivity for p-ANCAs, and one for c-ANCAs, and seven healthy volunteers. METHODS: A positive ANCA serology was determined with a standard indirect immunofluorescence assay. Purified immunoglobulins (IgGs) were prepared from serum samples by DEAE-Affigel blue chromatography. Human neutrophils were prepared by dextran-Ficoll-Hypaque separation. Superoxide anion (O2-.) generation was measured by following the superoxide dismutase inhibitable reduction of ferricytochrome. RESULTS: There were no significant differences among samples from ulcerative colitis IgG p-ANCA positive, ulcerative colitis IgG p-ANCA negative patients, and controls on O2-. production, whereas ANCA positive IgG from vasculitidis significantly enhanced O2-. release (p < 0.001). CONCLUSIONS: p-ANCAs associated with ulcerative colitis have no effect on the respiratory burst activity of normal human neutrophils in vitro. These results reinforce the hypotheses that ANCAs are unlikely to contribute to the pathogenesis of ulcerative colitis.

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Selected References

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  1. Bradford M. M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976 May 7;72:248–254. doi: 10.1006/abio.1976.9999. [DOI] [PubMed] [Google Scholar]
  2. Charles L. A., Caldas M. L., Falk R. J., Terrell R. S., Jennette J. C. Antibodies against granule proteins activate neutrophils in vitro. J Leukoc Biol. 1991 Dec;50(6):539–546. doi: 10.1002/jlb.50.6.539. [DOI] [PubMed] [Google Scholar]
  3. Davies D. J., Moran J. E., Niall J. F., Ryan G. B. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? 1982 Aug 28-Sep 4Br Med J (Clin Res Ed) 285(6342):606–606. doi: 10.1136/bmj.285.6342.606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Duerr R. H., Targan S. R., Landers C. J., Sutherland L. R., Shanahan F. Anti-neutrophil cytoplasmic antibodies in ulcerative colitis. Comparison with other colitides/diarrheal illnesses. Gastroenterology. 1991 Jun;100(6):1590–1596. doi: 10.1016/0016-5085(91)90657-7. [DOI] [PubMed] [Google Scholar]
  6. Ewert B. H., Jennette J. C., Falk R. J. Anti-myeloperoxidase antibodies stimulate neutrophils to damage human endothelial cells. Kidney Int. 1992 Feb;41(2):375–383. doi: 10.1038/ki.1992.52. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. Gross W. L., Schmitt W. H., Csernok E. ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol. 1993 Jan;91(1):1–12. doi: 10.1111/j.1365-2249.1993.tb03345.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hall J. B., Wadham B. M., Wood C. J., Ashton V., Adam W. R. Vasculitis and glomerulonephritis: a subgroup with an antineutrophil cytoplasmic antibody. Aust N Z J Med. 1984 Jun;14(3):277–278. doi: 10.1111/j.1445-5994.1984.tb03769.x. [DOI] [PubMed] [Google Scholar]
  11. Hardarson S., Labrecque D. R., Mitros F. A., Neil G. A., Goeken J. A. Antineutrophil cytoplasmic antibody in inflammatory bowel and hepatobiliary diseases. High prevalence in ulcerative colitis, primary sclerosing cholangitis, and autoimmune hepatitis. Am J Clin Pathol. 1993 Mar;99(3):277–281. doi: 10.1093/ajcp/99.3.277. [DOI] [PubMed] [Google Scholar]
  12. Jennette J. C., Falk R. J. Antineutrophil cytoplasmic autoantibodies in inflammatory bowel disease. Am J Clin Pathol. 1993 Mar;99(3):221–223. doi: 10.1093/ajcp/99.3.221. [DOI] [PubMed] [Google Scholar]
  13. Kallenberg C. G., Mulder A. H., Tervaert J. W. Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders. Am J Med. 1992 Dec;93(6):675–682. doi: 10.1016/0002-9343(92)90202-m. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. Rump J. A., Schölmerich J., Gross V., Roth M., Helfesrieder R., Rautmann A., Lüdemann J., Gross W. L., Peter H. H. A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology. 1990 Nov;181(4-5):406–413. doi: 10.1016/S0171-2985(11)80509-7. [DOI] [PubMed] [Google Scholar]
  17. Savage C. O., Pottinger B. E., Gaskin G., Pusey C. D., Pearson J. D. Autoantibodies developing to myeloperoxidase and proteinase 3 in systemic vasculitis stimulate neutrophil cytotoxicity toward cultured endothelial cells. Am J Pathol. 1992 Aug;141(2):335–342. [PMC free article] [PubMed] [Google Scholar]
  18. Saxon A., Shanahan F., Landers C., Ganz T., Targan S. A distinct subset of antineutrophil cytoplasmic antibodies is associated with inflammatory bowel disease. J Allergy Clin Immunol. 1990 Aug;86(2):202–210. doi: 10.1016/s0091-6749(05)80067-3. [DOI] [PubMed] [Google Scholar]
  19. Seibold F., Slametschka D., Gregor M., Weber P. Neutrophil autoantibodies: a genetic marker in primary sclerosing cholangitis and ulcerative colitis. Gastroenterology. 1994 Aug;107(2):532–536. doi: 10.1016/0016-5085(94)90181-3. [DOI] [PubMed] [Google Scholar]
  20. Shanahan F., Duerr R. H., Rotter J. I., Yang H., Sutherland L. R., McElree C., Landers C. J., Targan S. R. Neutrophil autoantibodies in ulcerative colitis: familial aggregation and genetic heterogeneity. Gastroenterology. 1992 Aug;103(2):456–461. doi: 10.1016/0016-5085(92)90834-l. [DOI] [PubMed] [Google Scholar]
  21. Shanahan F. Neutrophil autoantibodies in inflammatory bowel disease: are they important? Gastroenterology. 1994 Aug;107(2):586–589. doi: 10.1016/0016-5085(94)90189-9. [DOI] [PubMed] [Google Scholar]
  22. 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]

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