The presence of serum auto-antibodies targeting components of the neutrophil cytoplasm. The result given depends on the method of assay. An ELISA (or similar test) will give a quantitative value, i.e. a titre, signifying the dilution at which the test is still positive. In addition, the distribution of the antibodies can be examined using immunofluorescence with which anti-neutrophil cytoplasm antibody activity falls into 2 patterns:
- Anti-neutrophil cytoplasmic antibodies with cytoplasmic staining (c-ANCA) is a blood test used when considering the possibility of vasculitic disease, especially if Wegener's granulomatosis is in the differential diagnosis.
- The other main type of staining is perinuclear, so is called p-ANCA. This pattern is associated with antibodies to myeloperoxidase and is commonly seen in polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss syndrome and primary sclerosing cholangitis.
Further work has identified the targets of c-ANCA and p-ANCA. c-ANCA is associated with antibodies against neutrophil granulocyte proteinase-3 and is referred more specifically as PR3-ANCA. p-ANCA is associated with myeloperoxidase and is designated (MPO-ANCA). A further antigen, lysosome membrane protein-2 (LAMP-2), represents a further antigen target and may be implicated in certain forms of glomerulonephritis. An epitope on LAMP-2 shares homology with the bacterial adhesin FimH raising the possibility that antibodies against bacterial antigens may cross-react self-proteins resulting in auto-immune disease. Similarly, PR3-ANCA is thought to arise through cross-reactivity of antibodies produced against Staphylococcus aureus antigens.
- ↑ Kain R, Matsui K, Exner M, Binder S, Schaffner G, Sommer EM, Kerjaschki D. A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells. The Journal of experimental medicine. 1995 Feb 1; 181(2):585-97.
- ↑ Kain R, Exner M, Brandes R, Ziebermayr R, Cunningham D, Alderson CA, Davidovits A, Raab I, Jahn R, Ashour O, Spitzauer S, Sunder-Plassmann G, Fukuda M, Klemm P, Rees AJ, Kerjaschki D. Molecular mimicry in pauci-immune focal necrotizing glomerulonephritis. Nature medicine. 2008 Oct; 14(10):1088-96.(Link to article – subscription may be required.)
- ↑ Popa ER, Stegeman CA, Kallenberg CG, Tervaert JW. Staphylococcus aureus and Wegener's granulomatosis. Arthritis research. 2002; 4(2):77-9.