Skip to main content
Gut logoLink to Gut
. 1996 Mar;38(3):384–389. doi: 10.1136/gut.38.3.384

Importance of antineutrophil cytoplasmic antibodies in primary sclerosing cholangitis and ulcerative colitis: prevalence, titre, and IgG subclass.

D S Bansi 1, K A Fleming 1, R W Chapman 1
PMCID: PMC1383067  PMID: 8675091

Abstract

Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 87% of patients with primary sclerosing cholangitis with or without ulcerative colitis (PSC +/- UC) and in 68% of those with UC only. Compared with other liver and diarrhoeal diseases, ANCA have high specificity for PSC (+/- UC) and UC only. This study aimed to determine the prevalence and significance of ANCA in these two diseases and whether the ANCA titre or IgG subclass, or both, could distinguish between PSC + UC and UC only. Subjects included 63 patients with PSC, 85 with UC, 17 with coeliac disease, and 10 with dermatitis herpeteformis and 36 normal subjects. ANCA was detected using the immunoalkaline phosphatase method. The IgG subclass of ANCA was determined in 27 PSC + UC and 30 UC only patients using a panel of mouse monoclonal antibodies specific for the IgG subclasses. At a serum dilution of 1:5, ANCA had a diagnostic sensitivity of 65% for all PSC and 45% for UC only. For PSC + UC the sensitivity was 70% at 1:5 (p = 0.004 v UC only). At 1:50, the sensitivity values were 54% and 25% respectively for PSC + UC and UC only (p = 0.0006). In PSC, ANCA positivity was significantly associated with extensive involvement of the biliary tree but not with other clinical parameters. In UC only, the median disease duration was significantly greater in ANCA positive patients. The PSC + UC ANCA showed increased IgG3 compared with UC only ANCA (p < 0.05), together with increased IgG2 and IgG4 (p = NS). ANCA is a diagnostic marker in PSC and UC. While the higher titres and different IgG subclass distribution of ANCA in PSC + UC patients compared with those with UC only may reflect differences in underlying immune regulation, determination of the ANCA titre and IgG subclass is unlikely to have a role in distinguishing between PSC + UC and UC only ANCA. Future identification of the antigen(s) for ANCA should allow the development of a more sensitive and specific test for the diagnosis of these two conditions and also determine if ANCA is associated with UC or PSC.

Full text

PDF
389

Images in this article

Selected References

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

  1. 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]
  2. Chapman R. W., Arborgh B. A., Rhodes J. M., Summerfield J. A., Dick R., Scheuer P. J., Sherlock S. Primary sclerosing cholangitis: a review of its clinical features, cholangiography, and hepatic histology. Gut. 1980 Oct;21(10):870–877. doi: 10.1136/gut.21.10.870. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. 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]
  5. Ellerbroek P. M., Oudkerk Pool M., Ridwan B. U., Dolman K. M., von Blomberg B. M., von dem Borne A. E., Meuwissen S. G., Goldschmeding R. Neutrophil cytoplasmic antibodies (p-ANCA) in ulcerative colitis. J Clin Pathol. 1994 Mar;47(3):257–262. doi: 10.1136/jcp.47.3.257. [DOI] [PMC free article] [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. Halbwachs-Mecarelli L., Nusbaum P., Noël L. H., Reumaux D., Erlinger S., Grünfeld J. P., Lesavre P. Antineutrophil cytoplasmic antibodies (ANCA) directed against cathepsin G in ulcerative colitis, Crohn's disease and primary sclerosing cholangitis. Clin Exp Immunol. 1992 Oct;90(1):79–84. doi: 10.1111/j.1365-2249.1992.tb05835.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Jayne D. R., Weetman A. P., Lockwood C. M. IgG subclass distribution of autoantibodies to neutrophil cytoplasmic antigens in systemic vasculitis. Clin Exp Immunol. 1991 Jun;84(3):476–481. [PMC free article] [PubMed] [Google Scholar]
  9. Kaneko K., Suzuki Y., Yamashiro Y., Yabuta K. Is p-ANCA in ulcerative colitis directed against beta-glucuronidase? Lancet. 1993 Jan 30;341(8840):320–320. doi: 10.1016/0140-6736(93)92686-n. [DOI] [PubMed] [Google Scholar]
  10. Klein R., Eisenburg J., Weber P., Seibold F., Berg P. A. Significance and specificity of antibodies to neutrophils detected by western blotting for the serological diagnosis of primary sclerosing cholangitis. Hepatology. 1991 Dec;14(6):1147–1152. [PubMed] [Google Scholar]
  11. Lo S. K., Chapman R. W., Cheeseman P., Charlton C. P., Walker-Smith J. A., Mieli-Vergani G., Fleming K. A. Antineutrophil antibody: a test for autoimmune primary sclerosing cholangitis in childhood? Gut. 1993 Feb;34(2):199–202. doi: 10.1136/gut.34.2.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lo S. K., Fleming K. A., Chapman R. W. Prevalence of anti-neutrophil antibody in primary sclerosing cholangitis and ulcerative colitis using an alkaline phosphatase technique. Gut. 1992 Oct;33(10):1370–1375. doi: 10.1136/gut.33.10.1370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Mulder A. H., Horst G., Haagsma E. B., Limburg P. C., Kleibeuker J. H., Kallenberg C. G. Prevalence and characterization of neutrophil cytoplasmic antibodies in autoimmune liver diseases. Hepatology. 1993 Mar;17(3):411–417. [PubMed] [Google Scholar]
  14. Nässberger L., Ljungh A., Schumacher G., Kollberg B. beta-Glucuronidase antibodies in ulcerative colitis. Lancet. 1992 Sep 19;340(8821):734–735. doi: 10.1016/0140-6736(92)92279-o. [DOI] [PubMed] [Google Scholar]
  15. Peen E., Almer S., Bodemar G., Rydén B. O., Sjölin C., Tejle K., Skogh T. Anti-lactoferrin antibodies and other types of ANCA in ulcerative colitis, primary sclerosing cholangitis, and Crohn's disease. Gut. 1993 Jan;34(1):56–62. doi: 10.1136/gut.34.1.56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pokorny C. S., Norton I. D., McCaughan G. W., Selby W. S. Anti-neutrophil cytoplasmic antibody: a prognostic indicator in primary sclerosing cholangitis. J Gastroenterol Hepatol. 1994 Jan-Feb;9(1):40–44. doi: 10.1111/j.1440-1746.1994.tb01214.x. [DOI] [PubMed] [Google Scholar]
  17. Rubin R. L., Tang F. L., Chan E. K., Pollard K. M., Tsay G., Tan E. M. IgG subclasses of autoantibodies in systemic lupus erythematosus, Sjogren's syndrome, and drug-induced autoimmunity. J Immunol. 1986 Oct 15;137(8):2528–2534. [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. Schur P. H. IgG subclasses--a review. Ann Allergy. 1987 Feb;58(2):89-96, 99. [PubMed] [Google Scholar]
  20. Seibold F., Weber P., Klein R., Berg P. A., Wiedmann K. H. Clinical significance of antibodies against neutrophils in patients with inflammatory bowel disease and primary sclerosing cholangitis. Gut. 1992 May;33(5):657–662. doi: 10.1136/gut.33.5.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. TRUELOVE S. C., WITTS L. J. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br Med J. 1955 Oct 29;2(4947):1041–1048. doi: 10.1136/bmj.2.4947.1041. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Gut are provided here courtesy of BMJ Publishing Group

RESOURCES