Although antineutrophil cytoplasmic antibodies (ANCA) were first associated with the primary vasculitides, it is now clear that 15-20% of patients with lupus have detectable ANCA. In this short review we confirm that the major link is with perinuclear ANCA (pANCA) but not cytoplasmic ANCA (cANCA). ANCA to myeloperoxidaseare associatedwith drug-inducedlupus.There may be a link between pANCA levels and disease activity in some patients although the links to specific organ involvement are not proven. ANCA in lupus must be interpreted cautiously with particular attention paid to laboratorytechnique, the size, age and genetic backgroundof the populationsstudied.
Davies DJ , Niall JF.Segmental necrotizing glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology . Br Med J1982; 285: 606-606 .
2.
Savige J , Gatenby P.Anti-neutrophil cytoplasmic antibodies (ANCA): their detection and significance: report from workshops . Pathology1994; 26: 186-193 .
3.
Ardiles LG , Moya P , Mezzano A.Incidence and studies on antigenic specificities of antineutrophil-cytoplasmic antibodies (ANCA) in poststreptococcal glomerulonephritis . Clin Nephrol1997; 47: 1-15 .
4.
Jennette JC , Falk RJ , Andrassy Ket al.Nomenclature of systemic vasculitis. Proposal of an international consensus conference . Arthritis Rheum1994; 37: 187-192 .
5.
Drenkard C , Reyes E , Abello M , Alarcon-Segovia D.Vasculitis in systemic lupus erythematosus . Lupus1997; 6: 235-242 .
6.
Locke IC , Leaker B , Cambridge G.A comparison of the characteristics of circulating anti-myeloperoxidase in vasculitis with those in non vasculitic conditions . Clin Exp Immunol1999; 115: 369-376 .
7.
Ewert BH , Falk RJ.The pathogenetic role of antineutrophil cytoplasmic autoantibodies . Am J Kidney Dis1991; 18: 188-195 .
8.
Yang JJ , Preston GA , Pendergraft WFet al.Internalization of proteinase 3 is concomitant with endothelial cell apoptosis and internalization of myeloperoxidase with generatio of intracellular oxidants . Am J Pathol2001; 158: 581-592 .
9.
Savage CO , Pusey C , Pearson JD.Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens . Exp Nephrol1993; 1: 190-195 .
10.
Dolman KM , van de Wiel BA , Kam CMet al.Proteinase 3: substrate specificity and possible pathogenetic effect of Wegener’s granulomatosisautoantibodies by dysregulation of the enzyme . Adv Exp Med Biol1993; 336: 55-60 .
11.
Popa ER , Franssen CF , Limburg PCet al.In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3 and anti-myeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase . Arthritis Rheum2002; 46: 1894-1904 .
12.
Luzina IG , Knitzer RH , Atamas SPet al.Vasculitis in the Palmerston North mouse model of lupus: phenotype and cytokine production profile of infiltrating cells . Arthritis Rheum1999; 42: 561-568 .
13.
Saulot V , Vittecoq O , Salle Vet al.Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus . J Autoimmun2002; 19: 55-61 .
14.
Savige JA , Gillis D , Benson EBet al.International consensus statement on testing and reporting of antineutrophil cytoplasmic antibodies (ANCA) . Am J Clin Pathol1999; 111: 507-513 .
15.
Savage COS , Jones S , Marshall PD , Lockwood CM.Prospective study of radioimmunoassay for antibodies against neutrophil cytoplasm in diagnosis of systemic vasculitis . Lancet1987; 1: 1389-1393 .
16.
Falk RJ.Antineutrophil cytoplasmic autoantibodies with specificity for myeloperoxidase in patients with systemic and idiopathic necrotizing and crescentic glomerlonephritis . N Engl J Med1988; 318: 1651-1657 .
17.
Cambridge G , Wallace H , Bernstein RM , Weaker B.Autoantibodies to myeloperoxidase in idiopathic and drug-induced systemic lupus erythematosus and vasculitis . Br J Rheumatol1994; 33: 109-114 .
18.
Bang la Cour B , Hoier-Madsen M , Baslund B.Clinical correlates and substrate specificities of antibodies exhibiting neutrophil nuclear reactivity—a methodological study . J Immunol Methods1995; 187: 287-295 .
19.
Merkel PA , Polisson RP , Chang Y , Skates SJ , Niles JL.Prevalence of antineutrophil cytoplasmic antibodies in a large inception cohort of patients with connective tissue disease . Ann Intern Med1997; 126: 866-873 .
20.
Galeazzi M , Morozzi G , Sebastiani GDet al.Anti-neutrophil cytoplasmic antibodies in 566 European patients with systemic lupus erythematosus: prevalence, clinical associations and correlation with other autoantibodies. European Concerted Action on the Immunogenetics of SLE . Clin Exp Rheumatol1998; 16: 541-546 .
21.
Cooper T , Savige J , Nassis Let al.Clinical associations and characterisation of antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein and azurocidin . Rheumatol Int2000; 19: 129-136 .
22.
Zhao MH , Liu N , Zhang NK , Wang HY.Antineutrophil cytoplasmic autoantibodies (ANCA) and their target antigens in Chinese patients with lupus nephritis . Nephrol Dial Transplant1998; 13: 2821-2824 .
23.
Esnault VL , Short AK , Jones SJ , Skehel M , Walker J , Lockwood CM.Lactoferrin co-purifies with myeloperoxidase and is recognised by anti-neutrophil cytoplasm antibodies . Adv Exp Med Biol1993; 336: 101-104 .
24.
Jethwa HS , Nachman PA , Falk RJ , Jennette JC.False-positive myeloperoxidase binding activity due to DNA/anti-DNA antibody complexes: a source for analytical error in serologic evaluation of anti-neutrophil cytoplasmic autoantibodies . Clin Exp Immunol2000; 121: 544-550 .
25.
Manolova I , Dancheva M , Halacheva K.Antineutrophil cytoplasmic antibodies in patients with systemic lupus erythematosus: prevalence, antigen specificity, and clinical associations . Rheumatol Int2001; 20: 197-204 .
26.
Faure-Fontenla MA , Rodriguez-Suarez RS , Arias-Velasquez R , Garcia-Gonzalez JE.Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus in childhood . J Rheumatol1999; 26: 2480-2481 .
27.
Novo E , Garcia-MacGregor E , Nava S , Perini L.A possible defective estimation of antineutrophil cytoplasmic antibodies in systemic lupus erythematosus due to the coexistence of periodontitis: preliminary observations . P R Health Sci J1997; 16: 369-373 .
28.
Tan EM , Cohen AS , Fries JFet al.The 1982 revised criteria for the classification of systemic lupus erythematosus . Arthritis Rheum1982; 25: 1271-2177 .
29.
Chin HJ , Ahn C , Lim CSet al.Clinical implications of antineutrophil cytoplasmic antibody test in lupus nephritis . Am J Nephrol2000; 20: 57-63 .
30.
Nishiya K , Chikazawa H , Nishimura S , Hisakawa N , Hashimoto K.Anti-neutrophil cytoplasmic antibody in patients with systemic lupus erythematosus is unrelated to clinical features . Clin Rheumatol1997; 16: 70-75 .
31.
Sinico RA , Pozzi C , Radice Aet al.Clinical significance of antineutrophil cytoplasmic autoantibodieswith specificity for lactoferrin in renal diseases . Am J Kidney Dis1993; 22: 253-260 .
32.
Pozzi C , Rota S , Li Vecchi M , Sinico RA.Clinical significance of antilactoferrin antibodies in renal disease . Am J Kidney Dis1991; 18: 202-202 .
33.
Henshaw TJ , Malone CC , Gabay JE , Williams RC Jr.Elevations of neutrophil proteinase 3 in serum of patients with Wegener’s granulomatosis and polyarteritis nodosa . Arthritis Rheum1994; 37: 104-112 .
34.
Wong SN , Shah V , Dillon MJ.Anti-neutrophil cytoplasmic antibodies in childhoodsystemic lupus erythematosus . Eur J Pediatr1995; 154: 43-45 .
35.
Bombadier C , Urowitz MB , Caron D , Chang CH.Derivation of the SLEDAI: a disease activity index for lupus patients . Arthritis Rheum1992; 35: 630-640 .
36.
Bakkaloglu A , Topaloglu R , Saatci Uet al.Antineutrophil cytoplasmic antibodies in childhood systemic lupus erythematosus . Clin Rheumatol1998; 17: 265-267 .
37.
Nassberger L , Jonsson H , Sturfelt G , Akesson A.Autoantibodies against neutrophil cytoplasmic components in systemic lupus erythematosus and hydralazine-induced lupus . Clin Exp Immunol1990; 81: 380-383 .
38.
Hobbs RN , Bernstein RM.Antibodies to the five histones and poly [adenosine diphosphate ribose] in drug-induced lupus; implications for pathogenesis . Ann Rheum Dis1986; 46: 408-416 .
39.
Rubin RL , McNally EM , Nusinow SR , Searles P , Tam EM.Procainamide elicits a selective autoantibody response . Clin Exp Immunol1986; 63: 58-67 .
40.
Rubin RL , Burlingame RW.Autoantibodies associated with lupus induced by diverse drug targets a similar epitope in the H2A-H2B-DNA complex . J Clin Invest1992; 90: 165-173 .
41.
Bjorck S , Westberg G.Hydralazine-associated glomerulonephritis . Acta Med Scand1985; 218: 261-269 .
Nassberger L , Bjorck S , Sjoholm AG.Antibodies to neutrophil granulocyte myeloperoxidase and elastase; autoimmune responses in glomerulonephritis due to hydralazine treatment . J Int Med1991; 229: 261-265 .
44.
Almroth G , Hed J , Samuelson I.Sjostrom autoantibodies to leucocyte antigens in hydralazine associated nephritis . J Int Med1992; 231: 37-42 .
45.
Deng C , Zhang Z , Rao T , Attwood J , Yung R , Richardson B.Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling . Arthritis Rheum2003; 48: 746-756 .
46.
Herlin T , Wolthers OD , Heegaard NH , Wiik A.Anti-neutrophil cytoplasmic autoantibody (ANCA) profiles in propylthiouracil-induced lupus-like manifestations in monozygotic triplets with hyperthyroidism . Scand J Rheumatol2002; 31: 46-49 .
47.
Hay EM , Bacon PA , Gordon Cet al.The BILAG index: a reliable and valid instrument for measuring clinical disease activity in systemic lupus erythematosus . Quarterly J Med1993; 86: 447-458 .
48.
Lee SS , Lawton JW , Chan CE , Li CS , Kwan TH , Chau KF.Antilactoferrin antibody in systemic lupus erythematosus . Br J Rheumatol1992; 31: 669-673 .
49.
Chikazawa H , Nishiya K , Matsumori A , Hashimoto K.Immunoglobulin isotypes of anti-myeloperoxidase and anti-lactoferrin antibodies in patients with collagen diseases . J Clin Immunol2000; 20: 279-286 .
50.
Schnabel A , Csernok E , Isenberg DA , Mrowka C , Gross WZ.Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus. Prevalence, specificities, and clinical significance . Arthritis Rheum1995; 38: 633-637 .
51.
Spronk PE , Bootsma H , Horst Get al.Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus . Br J Rheumatol1996; 35: 625-631 .
52.
Committee ARAG.Dictionary of the Rheumatic Diseases. Signs and symptoms. 1st edn. Vol. 1. Contact Associates International Ltd: Bayport, NY , 1982.
53.
Mulder AH , van Leeuwen MA , Limburg PC , Kallenberg CG.Anti-neutrophil cytoplasmic antibodies in rheumatoid arthritis. Characterization and clinical correlations . Arthritis Rheum, 1993; 36: 1054-1060 .
54.
De Remee RA , Specks U.Lesions of the respiratory tract associated with the finding of anti-neytrophil cytoplasmic autoantibodies with a perinuclear pattern . Mayo Clin Proc1994; 69: 908-910 .
55.
Uesugi H , Ozaki S , Sobajima Jet al.Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases . J Rheumatol1998; 25: 703-709 .
56.
Ecklund SR , Saluta GS , Agudelo CA , Pisko EJ.Antineutrophil cytoplasmic antibodies: clinical characteristics of 10 patients with the perinuclear pattern of immunofluorescence on ANCA testing . South Med J1992; 85: 132-138 .
57.
Kuster S , Apenberg S , Andrassy K , Ritz E.Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus . Contrib Nephrol1992; 99: 94-98 .
58.
Pauzner R , Urowitz M , Gladman D , Gough J.Antineutrophil cytoplasmic antibodies in systemic lupus erythematosus . J Rheumatol1994; 21: 1670-1673 .
59.
Tervaert JW , Goldschmeding R , Elema JDet al.Association of autoantibodies to myeloperoxidase with different forms of vasculitis . Arthritis Rheum1990; 33: 1264-1272 .
60.
Savige JA , Chang L , Wilson D , Buchanan RR.Autoantibodies and target antigens in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides . Rheumatol Int1996; 16: 109-114 .
61.
Bygren P , Rasmussen N , Isaksson B , Wieslander J.Anti-neutrophil cytoplasm antibodies, anti-GBM antibodies and anti-dsDNA antibodies in glomerulonephritis . Eur J Clin Invest1992; 22: 783-792 .
62.
Tervaert JW , Mulder L , Stegeman Cet al.Occurrence of autoantibodies to human leucocyte elastase in Wegener’s granulomatosis and other inflammatory disorders . Ann Rheum Dis1993; 52: 115-120 .
Nassberger L , Sjoholm AG , Sturfelt G , Heubner A.Circulating anti-elastase in systemic lupus erythematosus . Lancet1989; 333: 509-509 .
65.
Esnault VLM , Keogan MT , Brownlee AA , Jayne DRW , Lockwood CT.Association of IgM with IgG ANCA in patients presenting with pulmonary haemorrhage . Kidney Int1992; 41: 1304-1310 .
66.
Kokolina E , Nusbaum P , Geffriaud C , Grunfeld JP , Halbwachs-Mecarelli L , Lesavre P.Isotype and affinity of antimyeloperoxidase autoantibodies in systemic vasculitis . Kidney Int1994; 46: 177-184 .
67.
Ronda N , Layward L , Sepe V , Allen A , Feehally J , Lockwood CM.Antineutrophil cytoplasmic antibodies (ANCA) of IgA isotype in adult Henoch-Schonlein purpura and IgA nephropathy . Clin Exp Immunol1994; 95: 49-55 .
68.
Sinico RA , Tadros M , Radiche Aet al.Lack of IgA antineutrophil cytoplasmic antibodies in Henoch-Schonlein purpura and IgA nephropathy . Clin Immunol Immunopath1994; 73: 19-26 .
69.
Jorgensen C , Bologna C , Brochier J , Sany J.IgA isotype rheumatoid factor in rheumatoid arthritis . Clin Exp Rheumatol1996; 14: 301-304 .
70.
Fanapoulos D , Varga J , Teoderescu M.High frequency of abnormal levels in IgA anti-beta 2-glycoprotein I antibodies in patients with systemic lupus erythematosus. Relationship with antiphospholipid syndrome . J Rheumatol1998; 25: 675-680 .
71.
Hildebrandt S , Senecal JL , Noell S , Daniels L , Earnshaw WC , Rothfield NF.The IgG, IgM, and IgA isotypes of anti-topoisomerase I and anticentromere antibodies . Arthritis Rheum1990; 33: 724-727 .
72.
Pourmand N , Wahren-Herlenius M , Gunnarsson Iet al.Ro/SSA and La/SSB specific IgA autoantibodies in serum of patients with Sjogren’s and systemic lupus erythematosus . Ann Rheum Dis1999; 58: 623-629 .
