Antineutrophil cytoplasmic antibody (ANCA)

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1 Antineutrophil cytoplasmic antibody (ANCA) ANCA 1982 Davies segmental sclerosing cholangitis [1-3] Antineutrophil cytoplasmic antibody ( ANCA) II F PR3 MPO Wegener's granulomatosis (WG) microscopic polyangiitis (MPA) Churg- - Strauss syndrome (CSS) C- (Enzyme linked immunosorbent WG assay; ELISA) ANCA 1999 International C- Consensus Statement on Testing and Reporting of WG ANCA necrotizing glomerulonephritis (indirect immunofluorescence; II F) (cytokines) Hall ANCA PR3 MPO Van der Woude 1985 WG ANCA Falk Jennette 1988 necrotizing reactive oxygen species (ROS) (lysosomal enzyme) glomerulonephritis MPA myeloperoxidase (MPO) P Goldschmeding WG proteinase 3 (PR3) C- (degranulation) PR3 MPO ANCA ANCA inflammatory bowel disease primary (apoptosis) PR3 64

2 MPO (in situ) a. C-ANCA (cytoplasmic-anca) -1 (monocyte PR3 chemoattractant protein-1) IL-8 b.p-anca (perinuclear-anca) (granuloma formation) [4] c. ANCA (atypical ANCA or x-anca) Tervaert Wegener's granulomatosis [5] 2. (ELISA) (proinflammatory cytokines) IL-1 TNF-α (upregulation) (polymorphonuclear neutrophils; PMNs) PR3 MPO PR3 PMNs [6] capture ELISAs ELISA plate PR3 staphylococcal superantigens (SAgs) SAg-reactive help- er T cells PR3-specific B cells ANCA 1999 International PMNs ROS Consensus Statement on Testing and Reporting of SAgs autospecific T cells B - (antigen-presenting cells) autoreactive T-cell activation II F 10% II F ANCA MPO native configuration PR3 [7-8] ANCA ANA ELISAs PR3- MPO-ANCA ANA 1. (II F) WG MPA II F ANA ANA P-ANCA ANA ELISAs ANCA II F 65

3 ANCA ANA II F titration ELISAs ANCA 5% ELI- SAs C- assay interlobular accentuation C-ANCA (atypical) WG 85% II F P- C- WG 58% atypical [9] Rao 28% 92% [10] MPO- ELISA MPA 23% 75% [11] PR3- MPO- C- ELISA WG % 1999 International WG MPA Consensus Statement the European standard- ization trials II ANCA [3] ANCA 1.C- WG 73% MPA 67% (pulmonary-renal 2.P- active idiopathic pauci-immune necrotizing cresentic glomerulonephritis syndrome) 80% MPA 50% CSS 70 80% (Subglottic tracheal stenosis) (Mononeuritis multiplex) (Retro-orbital mass) [3] Westman capture ELISA WG C- F ELISAs PR3- MPO-ANCA [12] 1 C- WG 80 90% MPA primary pauciimmune crescentic glomerulonephritis 20 40% CSS 35% 2.P-ANCA MPA primary pauciimmune crescentic glomerulonephritis 50% CSS 35% 3.C-ANCA(atypical) Cystic fibrosis 80% inflammatory bowel disease 66

4 primary sclerosing cholangitis 4.Atypical ANCA Russell inflammatory bowel disease 2001 Arthritis and Rheumatism [3] PR3-subset WG [15] PR3-ANCA WG MPA CSS subsets PR3 ANCA-associated vasculitides PR3 ( rpr3) N (N-terminal activation dipeptide) C-WG 100 WG ( 85 PR3- capture ELISA rpr3 pro-rpr3 ANCA-associated vasculitides C- ANCA prorpr3 PR3- WG C-ANCA WG (P 0.016) WG rpr3 Langford ANCA WG pro-rpr3 PR3- WG ANCA subsets titer [15] PR3- ANCA Langford 18 44% titer WG titer WG [13] Boomsma 206. II F antigen-specific ELISA WG MPO-ANCA) ( 92%) ANCA ELISA II F WG [14] PR3 (pro-rpr3) 1. Hoffman, Gary S: Antineutrophil cytoplasmic antibodies. Arthritis and Rheum 1998, 41(9): Franssen, Casper FM et al: Antiproteinase 3- and antimyeloperoxidase-associated vasculitis. Kidney Int 2000, 57(6): Savige, Judy: Antineutrophil cytoplasmic antibodies and associated diseases: A review of the clinical and laboratory features. Kidney Int 57(3): Hewins, Peter MRCP: Is Wegener's granulomatosis an autoimmune disease? Curr opin Rheumatol (1): Tervaert, Jan Willem Cohen: The role of superantigens in vasculitis. Curr opin Rheumatol (1): Bandt M de. et al: Induction of interleukin-1 and subsequent tissue factor expression by anti-proteinase 3 antibodies in human umbilical vein endothelial cells. Arthritis Rheum 1997, 40: Kallenberg, Cees GM: What is new with anti-neutrophil cytoplasmic antibodies: diagnostic, pathogenetic and therapeutic implications. Curr Opin Nephrol Hypertens 1999; 8(3): Nash: Antineutrophil cytoplasm antibodies and vasculitis. Arch Dis Child 1997; 77(3):

5 9. Westman KWA, Bygren PG, Olsson H, Ranstam J, Wieslander J: Relapse rate, renal survival and cancer morbidity in patients with Wegener's granulomatosis or microscopic polyangiitis with renal involvement. J Am Soc Nephrol 1998; 9: Rao JY, Weinberger M, Oddone EZ, Allen NB, Landsman P, Feussner JR: The role of antineutrophil cytoplasmic antibody testing in the diagnosis of Wegener granulomatosis. Ann Intern Med 1995; 123: Adu D, Pall A, Luqmani RA, Richards NT, Howie AJ, Emergy P: Controlled trial of pulse versus continuous prednisolone and cyclophosphamide in the treatment of systemic vasculitis. QJM 1997; 90: Hagen EC: Standardisation of solid phase assays for ANCA determination. Nephrology 1997; 3(Suppl): S Langford, Carol A; Hoffman, Gary S: Wegener's granulomatosis. Thorax 1999; 54(7): Boosma MM, Stegeman CA, van der Leij MJ, et al: Prediction of relapses in Wegener's granulomatosis by measeurememt of antineutrophil cytoplasmic antibody levels: a prospective study. Arthritis Rheum 2000; 43(9): Russell, KA, Fass DN, Specks U: Antineutrophil Cytoplasmic Antibodies Reacting With the Pro Form of Proteinase 3 and Disease Activity in Patients With Wegener's Granulomatosis and Microscopic Polyangiitis. Arthritis Rheum 2001; 44(2):

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