Antineutrophil Cytoplasmic Autoantibody, Cytoplasmic (c-ANCA)
- Author: Roman Bronfenbrener, MD; Chief Editor: Eric B Staros, MD more...
Antineutrophil cytoplasmic antibodies (ANCA) are found in several vasculitic conditions, including granulomatosis with polyangiitis, microscopic polyangiitis, and Churg-Strauss syndrome. Cytoplasmic ANCA (c-ANCA) represents a subset of these antibodies, in which the primary molecular target is proteinase-3 within the cytoplasm of neutrophils and monocytes. The role of c-ANCA in Wegener granulomatosis (WG) is unclear and unlikely to be pathogenic, as high titers do not correlate well with disease severity and may remain positive even with treatment and remission.
An absence of c-ANCA or titers less than 1:20 are generally considered a negative result. However, different laboratories may have different upper limits of normal, and any individual result should be interpreted through the reference range of the performing lab.
c-ANCA testing is performed in the initial evaluation and follow-up of patients with granulomatosis with polyangiitis (GPA), previously known as Wegener granulomatosis. This testing is performed in a 2-step approach. First, indirect fluorescent antibody detects the presence of antinuclear cytoplasmic antibodies; this positive result is followed by ELISA testing for presence and titer of antibodies specifically against proteinase-3.
In diagnosing GPA, the c-ANCA results should be interpreted while considering the patient’s presentation. In those with currently active systemic disease, elevated c-ANCA titers are over 98% sensitive and specific for GPA. In patients with limited disease, with an atypical presentation, or without the full spectrum of GPA manifestations, the sensitivity drops to 60-70%.[4, 5, 6] For further details about classifying disease severity and presentation, see the topic Wegener Granulomatosis.
In patients with positive c-ANCA, the level of titer elevation is a poor indicator of disease activity. Patients currently in remission may have persistent, several-fold elevations in c-ANCA titer; most of these patients do not develop a relapse in the future. Conversely, patients with rapidly declining titers may have persistent residual disease. The elevation in titer can, however, be used for increased vigilance during patient follow-up, with the intent of maintaining a higher index of suspicion for a relapse in patients with persistently raised levels. c-ANCA titers serve no role in dictating treatment and cannot be used to guide immunomodulatory therapy or deliver prognostic information to the patient.[1, 7]
The use of serial c-ANCA titers in following patients with established vasculitis for evidence of relapse has been a controversial issue. Although some studies have shown value in following titers, the high incidence of false-positive and false-negative results precludes a general recommendation. As such, the patient’s current symptoms and other lab studies are a better indicator of relapsing disease.[1, 8]
Collection and Panels
c-ANCA is performed on serum drawn during a random spot test.
Invalidation: Lipemia, gross hemolysis, bacterial contamination
Storage conditions: Refrigerated
Panels: c-ANCA is usually performed as a reflex test after a positive ANCA indirect immunofluorescence panel.
Granulomatosis with polyangiitis is a rare, necrotizing form of small-vessel vasculitis that classically manifests as a pulmonary-renal syndrome; patients develop hemoptysis and dyspnea, sinusitis and epistaxis, and frequently a rapidly progressive glomerulonephritis. Patients may also have ocular, cutaneous, neuropathic, and rheumatologic findings.[1, 9, 10, 11, 12]
Antineutrophil cytoplasmic antibodies (ANCA) are found in several vasculitic conditions, including granulomatosis with polyangiitis, microscopic polyangiitis, and Churg-Strauss syndrome. c-ANCA represents a subset of these antibodies, in which the primary molecular target is proteinase-3 within the cytoplasm of neutrophils and monocytes. The role of c-ANCA in WG is unclear and unlikely to be pathogenic, as high titers do not correlate well with disease severity and may remain positive even with treatment and remission.
c-ANCA is drawn during the evaluation of a patient with signs and symptoms suspicious for WG. After a c-ANCA returns back positive, frequently a tissue biopsy is needed to firmly establish the diagnosis.
c-ANCA has a specificity approaching 100%, especially in patients with active disease. However, several conditions may very rarely result in a false positive result. These include tuberculosis, Hodgkin disease, HIV infection, and multiple myeloma.
Langford, Carol A., and Fauci, Anthony S. The Vasculitis Syndromes. Harrison's Principles of Internal Medicine. 17th ed. 2119-2124.
Falk RJ, Gross WL, Guillevin L, Hoffman G, Jayne DR, Jennette JC. Granulomatosis with polyangiitis (Wegener's): an alternative name for Wegener's granulomatosis. Ann Rheum Dis. 2011 Apr. 70(4):704. [Medline].
Sinico RA, Radice A. Antineutrophil cytoplasmic antibodies (ANCA) testing: detection methods and clinical application. Clin Exp Rheumatol. 2014 May-Jun. 32(3 Suppl 82):S112-7. [Medline].
Cohen Tervaert JW, Damoiseaux J. Antineutrophil Cytoplasmic Autoantibodies: How Are They Detected and What Is Their Use for Diagnosis, Classification and Follow-up?. Clin Rev Allergy Immunol. 2012 Jun 6. [Medline].
Jennette JC, Falk RJ. Antineutrophil Cytoplasmic Antibodies: Discovery, Specificity, Disease Associations and Pathogenic Potential. Adv Pathol Lab Med. 1995. 8:363-78.
Finkielman JD, Lee AS, Hummel AM, Viss MA, Jacob GL, Homburger HA. ANCA are detectable in nearly all patients with active severe Wegener's granulomatosis. Am J Med. 2007 Jul. 120(7):643.e9-14. [Medline].
Finkielman JD, Merkel PA, Schroeder D, Hoffman GS, Spiera R, St Clair EW. Antiproteinase 3 antineutrophil cytoplasmic antibodies and disease activity in Wegener granulomatosis. Ann Intern Med. 2007 Nov 6. 147(9):611-9. [Medline].
Boomsma MM, Stegeman CA, van der Leij MJ, Oost W, Hermans J, Kallenberg CG. Prediction of relapses in Wegener's granulomatosis by measurement of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis Rheum. 2000 Sep. 43(9):2025-33. [Medline].
Zhang Y, Shi W, Tang S, Li J, Yin S, Gao X, et al. The influence of cathelicidin LL37 in human anti-neutrophils cytoplasmic antibody (ANCA)-associated vasculitis. Arthritis Res Ther. 2013 Oct 24. 15(5):R161. [Medline]. [Full Text].
Nohr E, Girard L, James M, Benediktsson H. Validation of a histopathologic classification scheme for antineutrophil cytoplasmic antibody-associated glomerulonephritis. Hum Pathol. 2014 Jul. 45(7):1423-9. [Medline].
Tonneijck L, Tanna A, Pusey CD. Antineutrophil cytoplasm antibody-positive pulmonary-renal syndrome in a patient with diffuse cutaneous systemic sclerosis. BMJ Case Rep. 2013 Jun 13. 2013:[Medline].
Srivastava A, Rao GK, Segal PE, Shah M, Geetha D. Characteristics and outcome of crescentic glomerulonephritis in patients with both antineutrophil cytoplasmic antibody and anti-glomerular basement membrane antibody. Clin Rheumatol. 2013 Sep. 32(9):1317-22. [Medline].
Rao JK, Weinberger M, Oddone EZ, Allen NB, Landsman P, Feussner JR. The role of antineutrophil cytoplasmic antibody (c-ANCA) testing in the diagnosis of Wegener granulomatosis. A literature review and meta-analysis. Ann Intern Med. 1995 Dec 15. 123(12):925-32. [Medline].