Introduction Autoimmune diseases Autoantibodies - Introduction Autoantibodies - Determination   Autoantibodies Rheumatoid Factor Antinuclear Antibodies (ANA) Specific Antibodies Anti-neutrophil Cytoplasmic Antibodies (ANCA) Anti-phospholipid Antibodies Anti-mitochondrial Antibodies (AMA) Anti-endothelial Cell Antibodies (AECA) Anti CCP antibodies Antibodies against DNases   Quality Assurance   Reference ranges   Algorithm ANA and incidence of diseases Proposed stepwise diagnosis scheme Positive Immunoflourescence - Nucleoplasmic Positive Immunoflourescence - Nucleolar Positive Immunoflourescence - Cytoplasmic Type of autoimmune diseases Conditions associated with antinuclear antibodies (ANA)   Slide show   References   Collaborators	References   Tomer Y, Buskila, D, Shoenfeld Y. Pathogenic significance and diagnostic value of lupus autoantibodies. Int Arch Allergy Immunol 1993; 100:293-8. Steinberg AD. Mechanism of disordered immune regulation. In: Stites DP, Terr AI, editors, 1986; 432-7. Rose HM, Ragan C, Pearce E, Lipman MO. Differential agglutination of normal and sensitized sheep erythrocytes by sera of patients with rheumatoid arthritis. Proc Soc Exp Biol Med 1948; 68:1-6. Hargraves MM, Richmond H, Morton R. Presentation of two bone marrow elements: the 'tart' cell and 'LE' cell. Proc Staff Meet Mayo Clin 1948; 23-5. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31:315-24. Cardon, DA. Rheumatoid Factor. In Kelley WN, Harris ED, Ruddy S, Sledge CB, eds. Textbook of Rheumatology, 4th ed. Philadelphia: Saunders, 1993: 155-63. Shmerling RH, Delbanco TL The rheumatoid factor: an analysis of clinical utility. Am J Med 1991; 1:528-34. Jacoby RK, Jayson MIV, Cosh JA. Onset, early stages, and prognosis of rheumatoid arthritis: a clinical study of 100 patients with 11-year follow-up. Br Med J. 1973; 2:96-1 00. Heimer R, Lein FM. On the distribution of rheumatoid factor among the immunoglobulins. Immunochemistry 1966; 3:1- 10. Dunne JV, Cason DA, Spiegelberg HL, Alspaugh MA, Vaughan J. IgA rheumatoid factor in the serum and saliva of patients with rheumatoid arthritis and Sjögren's syndrome. Ann Rheum Dis 1979; 38: 161-6. Gioud-Paquel M, Auvinet U, Raffin T. IgM rheumatoid factor (RF), IgA RF, IgE RF, and IgG RF detected by ELIS,A in rheumatoid arthritis. Ann Rheum Dis 1987; 46:65-71. Bampton JLM, Cawston TE, Kyle, MV Hazleman BL. Measurement of rheumatoid factors by an enzyme linked immunosorbent assay (ELISA) and comparison with other methods. Ann Rheum Dis 1985; 44:14-9. Visser H, Gelinck LB, Kampfraath AH, Breedveld FC, Hazes JM. Diagnostic and prognostic characteristics of the enzyme linked immunosorbent rheumatoid factor assays in rheumatoid arthritis. Ann Rheum Dis 1996; 55:157-61. Teitsson I, Withrington RH, Seifert MH, Valdimarsson H. Prospective study of early rheumatoid arthritis. I. Prognostic value of lgA rheumatoid factor. Ann Rheum Dis 1984; 43:673-8. Withrington RH, Teitsson L, Valdimarsson H, Seifert MH. Prospective study of early rheumatoid arthritis fl Association of the rheumatoid factor isotypes with disease activity. Ann Rheum Dis 1984; 43:679-85. Amason JA, Jonsson TH, Brekkan A, Sigurjonsson K, Valdimarsson H. Relation between bone erosions and rheumatoid factor isotypes. Ann Rheum Dis 1987; 46:380-4. Houssien DA, Jonsson T, Davies E, Scott DL. Clinical significance of IgA rheumatoid factor subclasses in rheumatoid arthritis. J Rheumatol 1997; 24:2119-22. Jorgensen C, Legouff MC, Bologna C, Brochier J, Sany J. IgA isotype rheumatoid factor in rheumatopid arthritis: clinical implications. Clin Exp Rheumatol 1996; 14:301-4. Jonsson T, Arinbjarnarson S, Thorsteinsson J, Steinsson K, Geirsson AJ, Jonsson H, et al. Raised IgA rheumatoid factor but not IgM RF or IgG RF is associated with extraarticular manifestations in rheumatoid arthritis. Scand J Rheumatol 1995; 24:372-5. Di Franco M, Spadaro A, Mauceri MT, Cortese A, Guerrisi R, Ciocci A. Relationship of rheumatoid factor isotype levels with joint lesions detected by magnetic resonance imaging in early rheumatoid arthritis. Rev Rhum Engl Ed 1999; 66:251-5. Kunkei HG, Muller-Eberhard HJ, Fudenberg HH, Tomasi TT. Gamma globulin complexes in rheumatoid arthritis and certain other conditions. J Clin Invest 1966; 40: 117-29. Carson DA, Lawrance S, Catalano MA, Vaughon JH, Abraham G. Radio-Imrnunoassay of IgG and 1gM rheumatoid factors reacting with human IgG. J lmmunol 1977; 19:295-300. Kallerup HE, Egeskjold EM, Graudal H. IgG, IgM and lgA rheumatoid factor in healthy adults and rheumatoid patients by an indirect immunofluorescence method, Scand J Rheumatol 1979; 8:1-9. Bampton JLM, Cawston TE, Kyle MV, Hazleman BL. Measurement of rheumatoid factors by an enzyme linked immunosorbent assay (ELISA) and comparison with other methods. Ann Rheum Dis 1985; 44:14-9. Gioud-Paquet M, Auvinet M, Raffin T. IgM rheumatoid factor (RF), IgA RF, lgE RF, and IgG RF detected by ELISA in rheumatoid arthritis. Ann Rheum Dis 1987; 46:65-71. Pope RM, McDuffy SJ. IgG rheumatoid factor. Relationship to seropositive rheumatoid arthritis and absence in seronegative disorders. Arthritis Rheum 1979; 22:988-98. Alleen C, Elson CJ, Scott DGI, Bacon PA, Bucknail RC. IgG anti-globulins in rheumatoid arthritis and other arthritides: relationship with clinical features and other parameters. Ann Rheum Dis 1981; 40:127-31. Nakamura RM, Tan EM. New developments in antinucleolar autoantibodies to nuclear antigens (ANA) in human diseases. In: Immunologic Analysis: Recent Progress in Diagnostic Laboratory Immunology. Eds. R.M. Nakamura, W.R. Dito, and E.S. Tucker III. Masson Publishing USA, Inc. New York, pp. 1-15. 1982. Fritzler MJ, Tan EM. Antibodies to histones in drug- induced and idiopathic lupus erythematosus. J Clin Invest 1978; 62:560-7. Tan EM, Rodnan GP, Garcia I, Moroi Y, Fritzler MJ, Peebles C. Diversity of antinuclear antibodies in progressive systemic sclerosis: Anticentromere antibody and its relationship to CREST syndrome. Arthritis Rheum 1980; 23:617-25. Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol 1978; 121:2228-34. McCarty GA, Valencia DW, Fritzler MJ. Antibody to the mitotic spindle apparatus: Immunologic characteristics and cytological studies. J Rheum 1984; 11:213-8. Tan EM, Feltkamp TE, Smolen JS, Butcher B, Dawkins R, Fritzler MJ, et al. Range of antinuclear antibodies in "healthy" individuals. Arthritis Rheum 1997; 40:1601-11. Perilloux BC, Shetty AK, Leiva LE, Gedalia A. Antinuclear antibody (ANA) and ANA profile tests in children with autoimmune disorders: a retrospective study. Clin Rheumatol 2000; 19:200-3. Tan EM, Rodnan GP, Garcia I, Moroi, Y, Fritzler MJ, Peebles C. Diversity of antinuclear antibodies in progressive systemic sclerosis: Anticentromere antibody and its relationship to CREST syndrome. Arthritis Rheum 1980; 23:617-25. Notman, DD, Kurata N, Tan EM. Profiles of antinuclear antibodies in systemic rheumatic diseases. Annals Intern Med 1975; 83:464-9. Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol 1978;121:2228-34. McCarty GA, Valencia DW, Fritzler MJ. Antibody to the mitotic spindle apparatus: Immunologic characteristics and cytologic studies. J Rheum 1984; 11:213-8. Ritchie RF. Antinucleolar antibodies: their frequency and diagnostic application. N Engl J Med 1970; 282:1174 Greenwald CA, Peebles CL, Nakamura RM. Laboratory Tests for antinuclear antibody (ANA) in rheumatic diseases. Lab Med 1978; 9:19-24. Cammarata RJ, Rodnan GP, Fennell RH. Serum-anti--globulin and antinuclear factors in the aged. JAMA 1967; 199:115-8. Taylor PV, Taylor KF, Norman A, Griffiths S, Scott JS. Prevalence of maternal Ro (SS-A) and La (SS- B) autoantibodies in relation to congenital heart block. Br J Rheumatol 1988; 27:128-32. Bossuyt X. Evaluation of two automated enzyme immunoassays for detection of antinuclear antibodies. Clin Chem Lab Med 2000; 38:1033-7. Lehmann HP, Fuhling I, Ott C, Hudepohl B, Haass M. HEp2 ANA EIA: a new fully utomated assay for the screening of antinuclear antibodies. Isr Med Assoc J 2000; 2:646-8. Bayer PM, Bauerfeind S, Bienvenu J, Fabien N, Frei PC, Gilburd B, et al. Multicenter evaluation study on a new HEP2 ANA screening enzyme immune assay. J Autoimmun 1999; 13:89-93. Tan EM, Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol 1966; 96:464-71. Harmon CE, Deng JS, Peebles CL, Tan EM. The importance of tissue substrate in the SS-A/Ro antigen-antibody system. Arthritis Rheum 1984; 27:166-73. Steitz JA, Wolin SL, Rinke J, Pettersson I, Mount SM, Lerner EA, Hinterberger M, Gottlieb E. Small ribonucleoproteins from eukaryotes: structures and roles in RNA biogenesis. Cold Spring Harb Symp Quant Biol 1983; 47:893-900. Craft J. Antibodies to snRNPs in systemic lupus erythematosus. Rheum Dis Clin North Am 1992; 18:311-35. Pettersson I, Hinterberger M, Mimori T, Gottlieb E, Steitz JA. The structure of mammalian small nuclear ribonucleoproteins. Identification of multiple protein components reactive with anti-(U1)ribonucleoprotein and anti-Sm autoantibodies. J Biol Chem 1984; 259:5907-14. Zampieri S, Ghirardello A, Doria A, Tonello M, Bendo R, Rossini K, et al. The use of Tween 20 in immunoblotting assays for the detection of autoantibodies in connective tissue diseases. J Immunol Methods 2000 May 26; 239:1-11. Habets WJ, de Rooij DJ, Hoet MH, van de Putte LB, van Venrooij WJ. Quantitation of anti-RNP and anti-Sm antibodies in MCTD and SLE patients by immunoblotting. Clin Exp Immunol 1985; 59:457-66. Pettersson I, Wang G, Smith EI, Wigzell H, Hedfors E, Horn J, et al. The use of immunoblotting and immunoprecipitation of (U) small nuclear ribonucleoproteins in the analysis of sera of patients with mixed connective tissue disease and systemic lupus erythematosus. A cross-sectional, longitudinal study. Arthritis Rheum 1986; 29:986-96. Weiner ES, Earnshaw WC, Senecal JL, Bordwell B, Johnson P, Rothfield NF. Clinical associations of anticentromere antibodies and antibodies to topoisomerase I. A study of 355 patients. Arthritis Rheum 1988; 31:378-85. Takeda Y, Wang GS, Wang RJ, Anderson SK, Pettersson I, Amaki S, et al. Enzyme-linked immunosorbent assay using isolated (U) small nuclear ribonucleoprotein polypeptides as antigens to investigate the clinical significance of autoantibodies to these polypeptides. Clin Immunol Immunopathol 1989; 50:213-3. Bridges AJ, Lorden TE, Havighurst TC. Autoantibody testing for connective tissue diseases. Comparison of immunodiffusion, immunoblot, and enzyme immunoassay. Am J Clin Pathol 1997;108:406-10. Sharp GC, Irvin WS, May CM, Holman HR, McDuffie FC, Hess EV, et al. Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systemic lupus erythematosus and other rheumatic disease. N Engl J Med 1976; 295: 1149-54. Satoh M, Richards HB, Hamilton KJ, Reeves WH. Human anti-nuclear ribonucleoprotein antigen autoimmune sera contain a novel subset of autoantibodies that stabilizes the molecular interaction of U1RNP-C protein with the Sm core proteins. Immunol 1997; 158:5017-25. Brahms H, Raymackers J, Union A, de Keyser F, Meheus L, Luhrmann R. The C-terminal RG dipeptide repeats of the spliceosomal Sm proteins D1 and D3 contain symmetrical dimethylarginines, which form a major B-cell epitope for anti-Sm autoantibodies. J Biol Chem 2000; 275:17122-9. Deng SX, Hanson E, Sanz I. In vivo cell penetration and intracellular transport of anti-Sm and anti-La autoantibodies. Int Immunol 2000; 12:415-23. Hoffman RW, Greidinger EL. Mixed connective tissue disease. Curr Opin Rheumatol 2000; 12:386-90. Nimelstein SH, Brody S, McShane D, Holman HR. Mixed connective tissue disease: a subsequent evaluation of the original 25 patients. Medicine 1980; 59:239-48. Margaux J, Hayem G, Palazzo E, Chazerain P, De Bandt M, Haim T, et al. Clinical usefulness of antibodies to U1snRNP proteins in mixed connective tissue disease and systemic lupus erythematosus.Rev Rhum Engl Ed 1998; 65:378-86. Hasegawa H, Uchiumi T, Sato T, Ofuchi Y, Murakami S, Honda S, et al. High frequency of antibody activity against ribosomal protein S10 in anti-Sm sera from patients with systemic lupus erythematosus. Lupus 1999; 8:439-43. Del Rincon I, Zeidel M, Rey E, Harley JB, James JA, Fischbach M, et al. Delineation of the human systemic lupus erythematosus anti-smith antibody response using phage-display combinatorial libraries. J Immunol 2000; 165:7011-6. Satoh M, Yamagata H, Watanabe F, Nakayama S, Ogasawara T, Tojo T, et al. Development of anti-Sm and anti-DNA antibodies followed by clinical manifestation of systemic lupus erythematosus in an elderly woman with long-standing Sjogren's syndrome. Lupus 1995; 4:63-5. Thompson D, Juby A, Davis P. The clinical significance of autoantibody profiles in patients with systemic lupus erythematosus. Lupus 1993; 2:15-9. Reichlin M. autoantibodies to the RoRNP particles. Clin Exp Immunol 1995; 99:7-9. Halse AK, Marthinussen MC, Wahren-Herlenius M, Jonsson R. Isotype distribution of anti-Ro/SS-A and anti-La/SS-B antibodies in plasma and saliva of patients with Sjogren's syndrome. Scand J Rheumatol 2000; 29:13-9. Lawrence S, Luy L, Laxer R, Krafchik B, Silverman E. The health of mothers of children with cutaneous neonatal lupus erythematosus differs from that of mothers of children with congenital heart block. Am J Med 2000; 108:705-9. Rosenthal E. New insights into the pathogenesis of anti-Ro antibody associated congenital complete heart block. Lupus 1998; 7:135-6. Mazel JA, El-Sherif N, Buyon J, Boutjdir M. Electrocardiographic abnormalities in a murine model injected with IgG from mothers of children with congenital heart block. Circulation 1999; 99:1914-8. Yukiko N. kDa and 60-kDa proteins and to SS-B 50-kDa protein in mothers of infants with neonatal lupus erythematosus. Br J Dermatol 2000; 142:908-12. Barland P, Lipstein E. Selection and use of laboratory tests in the rheumatic diseases. Am J Med 1996; 100:16S-23S. Parveen S, Morshed SA, Nishioka M. High prevalence of antibodies to recombinant CENP-B in primary biliary cirrhosis: nuclear immunofluorescence patterns and ELISA reactivities. J Gastroenterol Hepatol 1995; 10:438-45. Russo K, Hoch S, Dima C, Varga J, Teodorescu M. Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuse and limited systemic sclerosis, systemic lupus erythematosus, and rheumatoid arthritis. J Rheumatol 2000; 27:142-8. Spencer-Green G, Alter D, Welch HG. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med 1997; 103:242-8. Nakano M, Ohuchi Y, Hasegawa H, Kuroda T, Ito S, Gejyo F. Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus. J Rheumatol 2000; 27:1403-7. von Muhlen CA, Tan EM. Autoantibodies in the diagnosis of systemic rheumatic diseases. Semin Arthritis Rheum 1995; 24:323-58. Yeo JP, Toh BH. Cell cycle-associated autoantibodies: markers for autoimmunity and probes for molecular cell biology. Autoimmunity 1994; 18: 291-300. Chan EY, Mok TM, Lawton JW, Ko OK, Ho L, Lau CS. Comparison of counter immunoelectrophoresis with immunoblotting for detection of anti-extractable nuclear antigen antibodies in systemic lupus erythematosus. Asian Pac J Allergy Immunol 1999; 7:275-9. Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum 1996; 26:459-67. Nishikai M, Ohya K, Kosaka M, Akiya K, Tojo T. Anti-Jo-1 antibodies in polymyositis or dermatomyositis: evaluation by ELISA using recombinant fusion protein Jo-1 as antigen. Br J Rheumatol 1998; 37:357-61. Hirakata M, Suwa A, Nagai S, Kron MA, Trieu EP, Mimori T, et al. Anti-KS: identification of autoantibodies to asparaginyl-transfer RNA synthetase associated with interstitial lung disease. J Immunol 1999; 162:2315-20. Hilliquin P. Biological markers in inflammatory rheumatic diseases. Cell Mol Biol.1995; 41:993-1006. von Muhlen CA, Tan EM. Autoantibodies in the diagnosis of systemic rheumatic diseases. Semin Arthritis Rheum 1995; 24:323-58. Pincus T, Schur PH, Rose JA, Decker JL, Talal N. Measurement of serum DNA-binding activity in systemic lupus erythematosus. N Engl J Med 1969; 281:701-5. Nezlin R. A quantitative approach to the determination of antigen in immune complexes. J Immunol Methods 2000; 237:1-17. Radic MZ, Cocca BA, Seal SN. Initiation of systemic autoimmunity and sequence specific anti-DNA autoantibodies. Crit Rev Immunol 1999; 19:117-26. Massa M, De Benedetti F, Pignatti P, Albani S, Di Fuccia G, Monestier M, et al. Anti-double stranded DNA, anti-histone, and anti-nucleosome IgG reactivities in children with systemic lupus erythematosus. Clin Exp Rheumatol 1994; 12:219-25. Lightfoot RVV, Jr, Highes GRV. Significance of persisting serologic abnormalities in SLE. Arthritis Rheum. 1976; 19:837-43. Bruns A, Blass S, Hausdorf G, Burmester GR, Hiepe F: Nucleosomes are major T and B cell autoantigens in systemic lupus erythematosus. Arthritis Rheum 2000; 43:2307-15. Burlingame RW. The clinical utility of antihistone antibodies. Autoantibodies reactive with chromatin in systemic lupus erythematosus and drug-induced lupus. Clin Lab Med 1997;17367-78. Schett G, Rubin RL, Steiner G, Hiesberger H, Muller S, Smolen J. The lupus erythematosus cell phenomenon: comparative analysis of antichromatin antibody specificity in lupus erythematosus cell-positive and -negative sera. Arthritis Rheum 2000 ; 43:420-8. Molden DP, Klipple GL, Peebles CL, Rubin RL, Nakamura RM, Tan EM. IgM anti-histone H-3 antibody associated with undifferentiated rheumatic disease syndromes. Arthritis Rheum 1986; 29:39-46. Aarden LA, Lakmaker F, De Groot ER. Immunology of DNA. IV. Quantitative aspects of the Farr assay. J Immunol Methods 1976; 11:153-63. Hylkema MN, van Bruggen MC, ten Hove T, de Jong J, Swaak AJ, Berden JH, et al. Histone-containing immune complexes are to a large extent responsible for anti-dsDNA reactivity in the Farr assay of active SLE patients. J Autoimmun 2000; 14:159-68. Ginsberg B, Keiser H. A Millipore filter assay for antibodies to native DNA in sera of patients with systemic lupus erythematosus. Arthritis Rheum 1973; 16:199-207. Kredich NM, Skyler JS, Foote LJ. Antibodies to native DNA in systemic lupus erythematosus. A technique of rapid and quantitative determination. Arch Intern Med 1973; 131:639-44. Sontheimer RD, Gilliam JN. DNA antibody class, subclass, and complement fixation in systemic lupus erythematosus with and without nephritis. Clin Immunol Immunopathol 1978; 10:459-67. Pisetsky DS. Anti-DNA antibodies in systemic lupus erythematosus. Rheum Dis Clin North Am 1992; 18: 437-54. Ward MM, Pisetsky DS, Christenson VD. Antidouble stranded DNA antibody assays in systemic lupus erythematosus: correlations of longitudinal antibody measurements. J Rheumatol 1989; 16:609-13. Witte T, Hartung K, Matthias T, Sachse C, Fricke M, Deicher H, et al. Association of IgA anti-dsDNA antibodies with vasculitis and disease activity in systemic lupus erythematosus. SLE Study Group. Rheumatol Int 1998; 18:63-9. Tan EM, Smolen JS, McDougal JS, Butcher BT, Conn D, Dawkins R, et al. A critical evaluation of enzyme immunoassays for detection of antinuclear autoantibodies of defined specificities. I. Precision, sensitivity, and specificity. Arthritis Rheum 1999; 42:455-64. Egner W. The use of laboratory tests in the diagnosis of SLE. J Clin Pathol 2000; 53:424-32. James K, Carpenter AB, Cook L, Marchand R, Nakamura RM. Development of the antinuclear and anticytoplasmic antibody consensus panel by the Association of Medical Laboratory Immunologists. Clin Diagn Lab Immunol 2000; 7:436-43. Davies DJ, Moran JE, Niall JF, Ryan GB. Segmental necrotising glomerulonephritis with antineutrophil antibody: possible arbovirus aetiology? Br Med J (Clin Res Ed) 198; 285:606. Rump JA, Scholmerich J, Gross V, Roth M, Helfesrieder R, Rautmann A, et al. A new type of perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) in active ulcerative colitis but not in Crohn's disease. Immunobiology 1990; 181: 406-13. Hagen EC, Ballieux BE, van Es LA, Daha MR, van der Woude FJ. Antineutrophil cytoplasmic autoantibodies: a review of the antigens involved, the assays, and the clinical and possible pathogenetic consequences. Blood 1993; 81:1996-2002. van der Woude FJ. Anticytoplasmic antibodies in Wegener's granulomatosis. Lancet 1985; 2 (8445): 48. Gross WL, Ludemann G, Kiefer G, Lehmann H. Anticytoplasmic antibodies in Wegener's granulomatosis. Lancet 1986; 1 (8484): 806. Ludemann J, Utecht B, Gross WL. Anti-neutrophil cytoplasm antibodies in Wegener's granulomatosis recognize an elastinolytic enzyme. J Exp Med 1990; 171:357-62. Kao RC, Wehner NG, Skubitz KM, Gray BH, Hoidal JR. Proteinase 3. A distinct human polymorphonuclear leukocyte proteinase that produces emphysema in hamsters. J Clin Invest 1988; 82:1963-73. Jennette JC, Hoidal JR, Falk RJ. Specificity of anti-neutrophil cytoplasmic autoantibodies for proteinase 3. Blood 1990; 75:2263-4. Lesavre P, Noel LH, Chauveau D, Geffriaud C, Grunfeld JP. Antigen specificities and clinical distribution of ANCA in kidney diseases. Klin Wochenschr 1991; 69:552-7. Cohen Tervaert JW, van der Woude FJ, Fauci AS, Ambrus JL, Velosa J, Keane WF, et al. Association between active Wegener's granulomatosis and anticytoplasmic antibodies. Arch Intern Med 1989; 149:2461-5. Gross WL, Schmitt WH, Csernok E. ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol 1993; 91:1-12. 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. Ann Intern Med 1995; 23:925-32. Kallenberg CG, Mulder AH, Tervaert. Antineutrophil cytoplasmic antibodies: a still-growing class of autoantibodies in inflammatory disorders. Am J Med 1992; 93:675-82. Falk RJ, Jennette JC. The Third International Workshop on Antineutrophil Cytoplasmic Autoantibodies. Introduction. Am J Kidney Dis 1991;18:145-7. Gross WL, Hauschild S, Mistry N. The clinical relevance of ANCA in vasculitis. Clin Exp Immunol 1993;93 Suppl. 1:7-11. MacIsaac AI, Moran JE, Davies DJ, Murphy BF, Georgiou T, Niall JF. Antineutrophil cytoplasm antibody (ANCA) associated vasculitis. Clin Nephrol 1990 Jul; 34:5-8. Levy Y, Sherer Y, George J, Langevitz P, Ahmed A, Bar-Dayan Y, et al. Serologic and Clinical Response to Treatment of Systemic Vasculitis and Associated Autoimmune Disease with Intravenous Immunoglobulin. Int Arch Allergy Immunol 1999; 119:231-8. Nolle B, Specks U, Ludemann J, Rohrbach MS, DeRemee RA, Gross WL. Anticytoplasmic autoantibodies: their immunodiagnostic value in Wegener granulomatosis. Ann Intern Med 1989; 111:28-40. Cohen Tervaert JW, Huitema MG, Hene RJ, Sluiter WJ, The TH, van der Hem GK, et al. Prevention of relapses in Wegener's granulomatosis by treatment based on antineutrophil cytoplasmic antibody titre. Lancet 1990; 336:709-11. Kerr GS, Fleisher TA, Hallahan CW, Leavitt RY, Fauci AS, Hoffman GS. Limited prognostic value of changes in antineutrophil cytoplasmic antibody titer in patients with Wegener's granulomatosis. Arthritis Rheum 1993; 36:365-71. Gross WL, Schmitt WH, Csernok E. ANCA and associated diseases: immunodiagnostic and pathogenetic aspects. Clin Exp Immunol 1993; 91:1-12. Lesavre P. Antineutrophil cytoplasmic autoantibodies antigen specificity. Am J Kidney Dis 1991; 18:159-63. Schmitt WH, Csernok E, Flesch BK, Hauschild S, Gross WL. Autoantibodies directed against lysozyme: a new target antigen for anti-neutrophil cytoplasmic antibodies (ANCA). Adv Exp Med Biol 1993; 336:267-72. Andrassy K, Koderisch J, Schafer A, Waldherr R. Idiopathic rapidly progressive (crescentic) glomerulonephritis with myeloperoxidase antibodies--a new entity linked to female sex? Nephron 1990; 56:99-100. Gueirard P, Delpech A, Gilbert D, Godin M, Le Loet X, Tron F. Anti-myeloperoxidase antibodies: immunological characteristics and clinical associations. J Autoimmun 1991; 4:517-27. Cohen Tervaert JW, Goldschmeding R, Elema JD, Limburg PC, van der Giessen M, Huitema MG, et al. Association of autoantibodies to myeloperoxidase with different forms of vasculitis. Arthritis Rheum 1990; 33:1264-72. Cohen Tervaert JW, Limburg PC, Elema JD, Huitema MG, Horst G, The TH, Kallenberg CG. Detection of autoantibodies against myeloid lysosomal enzymes: a useful adjunct to classification of patients with biopsy-proven necrotizing arteritis. Am J Med 1991; 91:59-66. Kyndt X, Reumaux D, Bridoux F, Tribout B, Bataille P, Hachulla E, et al. Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis. Am J Med 1999; 106:527-33. Torffvit O, Thysell H, Nassberger L Occurrence of autoantibodies directed against myeloperoxidase and elastase in patients treated with hydralazine and presenting with glomerulonephritis. Hum Exp Toxicol 1994; 13:563-7. Jaunkalns R, Shear NH, Sokoluk B, Gardner D, Claas F, Uetrecht JP. Antimyeloperoxidase antibodies and adverse reactions to clozapine. Lancet 1992; 339: 1611-2. Kallenberg CG. Laboratory findings in the vasculitides. Baillieres Clin Rheumatol 1997; 11:395-421. Savige J, Neeson P, Trevisin M, Gambel P, Pollock W. ELISA is the superior method for detecting antineutrophil cytoplasmic antibodies in the diagnosis of systemic necrotising vasculitis. J Clin Pathol 2000; 53: 644-5. Geffriaud-Ricouard C, Noel LH, Chauveau D, Houhou S, Grunfeld JP, Lesavre P. Clinical significance of ANCA in 98 patients. Adv Exp Med Biol 1993; 336:273-9. Gross WL. Antineutrophil cytoplasmic autoantibody testing in vasculitides. Rheum Dis Clin North Am 1995; 21:987-1011. Asherson RA, Cervera R, Piette JC, Font J, Lie JT, Burcoglu A, et al. Catastrophic antiphospholipid syndrome. Clinical and laboratory features of 50 patients. Medicine (Baltimore) 1998;77:195-207. Triplett DA. Antiphospholipid-protein antibodies: laboratory detection and clinical relevance. Thromb Res 1995;78:1-31. Shah NM, Khamashta MA, Atsumi T, Hughes GR. Outcome of patients with anticardiolipin antibodies: a 10 year follow-up of 52 patients. Lupus 1998; 7:3-6. Buttgereit F, Grunewald T, Schuler-Maue W, Burmester GR, Hiepe F. Value of anticardiolipin antibodies for monitoring disease activity in systemic lupus erythematosus and other rheumatic diseases. Clin Rheumatol 1997; 16:562-9. Mehdi H, Aston CE, Sanghera DK, Hamman RF, Kamboh MI. Genetic variation in the apolipoprotein H (beta2-glycoprotein I) gene affects plasma apolipoprotein H concentrations. Hum Genet 1999; 105:63–71. Atsumi T, Tsutsumi A, Amengual O, Khamashta MA, Hughes GR, Miyoshi Y, et al. Correlation between beta2-glycoprotein I valine/leucine247 polymorphism and anti-beta2-glycoprotein I antibodies in patients with primary antiphospholipid syndrome. Rheumatology (Oxford) 1999,38:721–723. Hirose N, Williams R, Alberts AR, Furie RA, Chartash EK, Jain RI, et al. A role for the polymorphism at position 247 of the beta2-glycoprotein I gene in the generation of anti-beta2-glycoprotein I antibodies in the antiphospholipid syndrome. Arthritis Rheum 1999,42:1655–1661. Gushiken FC, Arnett FC, Thiagarajan P. Primary antiphospholipid antibody syndrome with mutations in the phospholipid binding domain of beta(2)-glycoprotein I. Am J Hematol 2000; 65:160-5. Falco M, Sorrenti A, Priori R, Luan FL, Pittoni V, Agresti MG, et al. Anti-cardiolipin antibodies in HIV infection are true antiphospholipids not associated with antiphospholipid syndrome. Ann Ital Med Int 1993; 8:171-4. Ordi J, Selva A, Monegal F, Porcel JM, Martinez-Costa X, Vilardell M. Anticardiolipin antibodies and dependence of a serum cofactor. A mechanism of thrombosis. J Rheumatol 1993; 20:1321-4. Galli M, Beretta G, Daldossi M, Bevers EM, Barbui T. Different anticoagulant and immunological properties of anti-prothrombin antibodies in patients with antiphospholipid antibodies. Thromb Haemost 1997; 77:486-91. Triplett DA, Asherson RA. Pathophysiology of the catastrophic antiphospholipid syndrome (CAPS). Am J Hematol 2000; 65:154-9. Munoz-Rodriguez FJ, Reverter JC, Font J, Tassies D, Cervera R, Espinosa G, et al. Prevalence and clinical significance of antiprothrombin antibodies in patients with systemic lupus erythematosus or with primary antiphospholipid syndrome. Haematologica 2000; 85:632-7. Lackner KJ, von Landenberg C, Barlage S, Schmitz G. Analysis of prothrombotic effects of two human monoclonal IgG antiphospholipid antibodies of apparently similar specificity. Thromb Haemost 2000; 83:583-8. Triplett DA. Use of the Dilute Russell Viper Venom Time (dRVVT): Its Importance and Pitfalls. J Autoimmun 2000; 15:173-8. McNeil HP, Chesterman CN, Krilis SA. Immunology and clinical importance of antiphospholipid antibodies. Adv Immunol 1991; 49:193-280. McNeil HP, Simpson RJ, Chesterman CN, Krilis SA. Anti-phospholipid antibodies are directed against a complex antigen that includes a lipid-binding inhibitor of coagulation: beta 2-glycoprotein I (apolipoprotein H). Proc Natl Acad Sci U S A 1990; 87:4120-4. Galli M, Comfurius P, Maassen C, Hemker HC, de Baets MH, van Breda-Vriesman PJ, et al. Anticardiolipin antibodies (ACA) directed not to cardiolipin but to a plasma protein cofactor. Lancet 1990; 335:1544-7. Matsuura E, Igarashi Y, Fujimoto M, Ichikawa K, Koike T. Anticardiolipin cofactor(s) and differential diagnosis of autoimmune disease. Lancet 1990; 336:177-8. Matsuura E, Igarashi Y, Yasuda T, Triplett DA, Koike T. Anticardiolipin antibodies recognize beta 2-glycoprotein I structure altered by interacting with an oxygen modified solid phase surface. J Exp Med 1994; 179:457-62. Biasiolo A, Rampazzo P, Brocco T, Barbero F, Rosato A, Pengo V. [Anti-beta2 glycoprotein I-beta2 glycoprotein I] immune complexes in patients with antiphospholipid syndrome and other autoimmune diseases. Lupus 1999; 8:121-6. Teixido M, Font J, Reverter JC, Cervera R, Tassies D, Ingelmo M, et al. Anti-beta 2-glycoprotein I antibodies: a useful marker for the antiphospholipid syndrome. Br J Rheumatol 1997; 36:113-6. Guerin J, Feighery C, Sim RB, Jackson J.Antibodies to beta2-glycoprotein I--a specific marker for the antiphospholipid syndrome. Clin Exp Immunol 1997; 109:304-9. Erickson EN Jr, Najmey SS, Keil LB, El-Kadi HS, DeBari VA. Reference calibrators for IgG antibodies to beta2-glycoprotein I: preparation, properties and availability to investigators. Clin Chem 1996; 42:1116-7. Brighton TA, Hogg PJ, Dai YP, Murray BH, Chong BH, Chesterman CN. Beta 2-glycoprotein I in thrombosis: evidence for a role as a natural anticoagulant. Br J Haematol 1996; 93:185-94. Tsutsumi A, Matsuura E, Ichikawa K, Fujisaku A, Mukai M, Kobayashi S, et al. Antibodies to beta 2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus. Arthritis Rheum 1996; 39:1466-7 Balestrieri G, Tincani A, Spatola L, Allegri F, Prati E, Cattaneo R, et al. Anti-beta 2-glycoprotein I antibodies: a marker of antiphospholipid syndrome? Lupus 1995; 4:122-30. Inanc M, Donohoe S, Ravirajan CT, Radway-Bright EL, Mackie I, Machin S, et al. Anti-beta2-glycoprotein I, anti-prothrombin and anticardiolipin antibodies in a longitudinal study of patients with systemic lupus erythematosus and the antiphospholipid syndrome. Br J Rheumatol 1998; 37:1089-94. Cucnik S, Ambrozic A, Bozic, B, Skitek M, Kveder T. Anti-ß2-Glycoprotein I ELISA: Methodology, Determination of Cut-off Values in 434 Helthy Caucasians and Evaluation of Monoclonal Antibodies as Possible International Standards. Clin Chem Lab Med 2000; 38:777-83. Sugi T, Katsunuma J, Izumi S, McIntyre JA, Makino T. Prevalence and heterogeneity of antiphosphatidylethanolamine antibodies in patients with recurrent early pregnancy losses. Fertil Steril 1999; 71:1060–1065. Lakos G, Kiss E, Regeczy N, Tarjan P, Soltesz P, Zeher M, et al.: Isotype distribution and clinical relevance of anti-beta2-glycoprotein I (beta2-GPI) antibodies: importance of IgA isotype. Clin Exper Immunol 1999; 117:574–579. Abinader A, Hanly AJ, Lozada CJ Catastrophic antiphospholipid syndrome associated with anti-beta2-glycoprotein I IgA [letter]. Rheumatology (Oxford) 1999; 38:84–85. Cucurull E, Gharavi AE, Diri E, Mendez E, Kapoor D, Espinoza LR. IgA anticardiolipin and anti-beta2-glycoprotein I are the most prevalent isotypes in African American patients with systemic lupus erythematosus Am J Med Sci 1999; 318:55–60. Diri E, Cucurull E, Gharavi AE, Kapoor D, Mendez EA, Scopelitis, et al. Antiphospholipid (Hughes') syndrome in African-Americans: IgA aCL and abeta2 glycoprotein-I is the most frequent isotype. Lupus 1999; 8:263–268. Mitchison HC, Palmer JM, Bassendine MF, Watson AJ, Record CO, James OF. A controlled trial of prednisolone treatment in primary biliary cirrhosis. Three-year results. J Hepatol 1992; 15:336-44. Wong RC, Wilson R, Neil J, Adelstein S, Silvestrini RA, Benson EM, Powell L .AMA-M2 do not directly produce ANCA indirect immunofluorescence patterns. J Clin Pathol 2000; 53:643. Klein R, Pointner H, Zilly W, Glassner-Bittner B, Breuer N, Garbe W, et al. Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years. Liver 1997; 17:119-28. Lanir N, Zilberman M, Yron I, Tennenbaum G, Shechter Y, Brenner B. Reactivity patterns of antiphospholipid antibodies and endothelial cells: effect of antiendothelial antibodies on cell migration. J Lab Clin Med 1998; 131548-56. Lee KH, Bang D, Choi ES, Chun WH, Lee ES, Lee S. Presence of circulating antibodies to a disease-specific antigen on cultured human dermal microvascular endothelial cells in patients with Behcet's disease. Arch Dermatol Res 1999; 291:374-81. Lee KH, Chung HS, Bang D, Lee S. Behcet's disease sera containing antiendothelial cell antibodies promote adhesion of T lymphocytes to cultured human dermal microvascular endothelial cells. Yonsei Med J 1999; 40:152-8. Gobel U, Eichhorn J, Kettritz R, Briedigkeit L, Sima D, Lindschau C, et al. Disease activity and autoantibodies to endothelial cells in patients with Wegener's granulomatosis. Am J Kidney Dis 1996; 28:186-94. Salojin KV, Le Tonqueze M, Saraux A, Nassonov EL, Dueymes M, Piette JC, et al. Antiendothelial cell antibodies: useful markers of systemic sclerosis. Am J Med 1997; 102:178-85. D'Cruz D, Khamashta M, Hughes G. Antiendothelial cell antibodies (AECA) in systemic lupus erythematosus (SLE). Clin Rev Allergy Immunol 1997; 15:53-63. Belizna C, Tervaert JW. Specificity, pathogenecity, and clinical value of antiendothelial cell antibodies. Semin Arthritis Rheum 1997; 27:98-109. Fujieda M, Oishi N, Kurashige T. Antibodies to endothelial cells in Kawasaki disease lyse endothelial cells without cytokine pretreatment. Clin Exp Immunol 1997; 107:120-6. Kaneko K, Savage CO, Pottinger BE, Shah V, Pearson JD, Dillon MJ. Antiendothelial cell antibodies can be cytotoxic to endothelial cells without cytokine pre-stimulation and correlate with ELISA antibody measurement in Kawasaki disease. Clin Exp Immunol 1994; 98:264-9. Meroni PL, D'Cruz D, Khamashta M, Youinou P, Hughes GRV. Anti-endothelial cell antibodies: only for scientists or for clinicians too? Clin Exp Immunol 1996; 104:199-202. Praprotnik S, Rozman B, Blank M, Shoenfeld Y. Pathogenic role of anti-endothelial cell antibodies in systemic vasculitis. Wien Klin Wochenschr 2000; 112:660-4. Pignone A, Scaletti C, Matucci-Cerinic M, Vazquez-Abad D, Meroni PL, Del Papa N, et al. Anti-endothelial cell antibodies in systemic sclerosis: significant association with vascular involvement and alveolo-capillary impairment. Clin Exp Rheumatol 1998;16:527-32. Filep JG, Bodolay E, Sipka S, Gyimesi E, Csipo I, Szegedi G. Plasma endothelin correlates with antiendothelial antibodies in patients with mixed connective tissue disease. Circulation 1995; 92:2969-74. Eichhorn J, Sima D, Lindschau C, Turowski A, Schmidt H, Schneider W, et al. Antiendothelial cell antibodies in thromboangiitis obliterans. Am J Med Sci 1998; 315:17-23. Pall AA, Savage COS. Mechanism of endothelial injury in vasculitis. Springer Semin Immunpathol 1994; 16:23-37. Youinou P, Revelen R, Bordron A. Is antiendothelial cell antibody the murder weapon in systemic sclerosis? Clin Exp Rheumatol 1999;17:35-6. D'Cruz D, Direskeneli H, Khamashta M, Hughes GR. Lymphocyte activation markers and von Willebrand factor antigen in Wegener's granulomatosis: potential markers for disease activity. J Rheumatol 1999; 26:103-9. Targoff IN: Humoral immunity in polymiositis/dermatomyositis. J Invest Dermatol 1993: 100:16S-23S. Rider LG, Miller FV, Targof IN, Sherry DD, Samayoa E, Lindahl M, et al. A broadend spectrum of juvenile myositis. Myositis specific autoantibodies in children. Arthritis Rheum 1994; 37: 1534-8 Schellekens GA, de Jong BA, van den Hoogen FH, van de Putte LB, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific autoantibodies. J Clin Invest. 1998 Jan 1;101(1):273-81. van Gaalen FA, Linn-Rasker SP, van Venrooij WJ, de Jong BA, Breedveld FC, Verweij CL, Toes RE, Huizinga TW. Autoantibodies to cyclic citrullinated peptides predict progression to rheumatoid arthritis in patients with undifferentiated arthritis: a prospective cohort study. Arthritis Rheum. 2004 Mar;50(3):709-15. Bombardieri M, Alessandri C, Labbadia G, Iannuccelli C, Carlucci F, Riccieri V, Paoletti V, Valesini G. Role of anti-cyclic citrullinated peptide antibodies in discriminating patients with rheumatoid arthritis from patients with chronic hepatitis C infection-associated polyarticular involvement. Lopez-Hoyos M, Ruiz De Alegria C, Blanco R, Crespo J, Pena M, Rodriguez-Valverde V, Martinez-Taboada VM. Clinical utility of anti-CCP antibodies in the differential diagnosis of elderly-onset rheumatoid arthritis and polymyalgia rheumatica. Rheumatology (Oxford). 2004 Feb 17 Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, Habibuw MR, Vandenbroucke JP, Dijkmans BA. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum. 2004 Feb;50(2):380-6. Saraux A, Berthelot JM, Devauchelle V, Bendaoud B, Chales G, Le Henaff C, Thorel JB, Hoang S, Jousse S, Baron D, Le Goff P, Youinou P. Value of antibodies to citrulline-containing peptides for diagnosing early rheumatoid arthritis. J Rheumatol. 2003 Dec;30(12):2535-9. Wilber A, O'Connor TP, Lu ML, Karimi A, Schneider MC. Dnase1l3 deficiency in lupus-prone MRL and NZB/W F1 mice. Clin Exp Immunol. 2003 Oct;134(1):46-52. Yasutomo K, Horiuchi T, Kagami S, Tsukamoto H, Hashimura C, Urushihara M, Kuroda Y. Mutation of DNASE1 in people with systemic lupus erythematosus. Nat Genet. 2001 Aug;28(4):313-4. Yeh TM, Chang HC, Liang CC, Wu JJ, Liu MF. Deoxyribonuclease-inhibitory antibodies in systemic lupus erythematosus. Biomed Sci. 2003 Sep-Oct;10(5):544-51. Napirei M, Karsunky H, Zevnik B, Stephan H, Mannherz HG, Moroy T. Features of systemic lupus erythematosus in Dnase1-deficient mice. Nat Genet. 2000 Jun;25(2):177-81 Lachmann PJ. Lupus and desoxyribonuclease. Lupus. 2003;12(3):202-6