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Autoantibodies in Systemic Sclerosis

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Systemic Sclerosis

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Abstract

Systemic sclerosis (SSc) is a multisystem connective tissue disorder characterized by microvascular damage and excessive fibrosis of the skin and internal organs. SSc is believed to be an autoimmune disease because of the presence of antinuclear antibodies (ANAs). ANAs are detected in more than 90 % of patients with SSc. Although the role of ANAs in the pathogenesis in SSc has not been clarified, each ANA is closely associated with specific clinical features. Therefore, it is clinically useful to classify the patients based on the type of ANAs for diagnosis and management of such patients. Anti-centromere antibodies (Abs), anti-DNA topoisomerase I Abs, and anti-RNA polymerase III Abs are representative ANAs found in patients with SSc. Other serum ANAs detected in SSc include those targeted against Th/To, U3 RNP, human upstream-binding protein, U11/U12 RNP, U1 RNP, Ku, PM-Scl, and RuvBL1/2. The prevalence of each of the ANAs and the clinical characteristics are reportedly dependent on ethnicity. Identifying several ANAs requires immunoprecipitation assays. Establishment of an easy and simple screening system for ANA specificities such as an enzyme-linked immunosorbent assay is expected.

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References

  1. LeRoy EC, Black C, Fleischmajer R, et al. Scleroderma (systemic sclerosis): classification, subsets, and pathogenesis. J Rheumatol. 1988;15:202–5.

    CAS  PubMed  Google Scholar 

  2. Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151.

    Article  CAS  PubMed  Google Scholar 

  3. Fanning GC, Welsh KI, Bunn C, et al. HLA associations in three mutually exclusive autoantibody subgroups in UK systemic sclerosis patients. Br J Rheumatol. 1998;37:201–7.

    Article  CAS  PubMed  Google Scholar 

  4. Okano Y. Antinuclear antibody in systemic sclerosis (scleroderma). Rheum Dis Clin North Am. 1996;22:709–35.

    Article  CAS  PubMed  Google Scholar 

  5. Kaji K, Fertig N, Medsger Jr TA, et al. Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement. Arthritis Care Res. 2014;66:575–84.

    Article  CAS  Google Scholar 

  6. Steen VD. Autoantibodies in systemic sclerosis. Semin Arthritis Rheum. 2005;35:35–42.

    Article  CAS  PubMed  Google Scholar 

  7. Kuwana M, Kaburaki J, Okano Y, et al. Clinical and prognostic associations based on serum antinuclear antibodies in Japanese patients with systemic sclerosis. Arthritis Rheum. 1994;37:75–83.

    Article  CAS  PubMed  Google Scholar 

  8. Hamaguchi Y, Hasegawa M, Fujimoto M, et al. The clinical relevance of serum antinuclear antibodies in Japanese patients with systemic sclerosis. Br J Dermatol. 2008;158:487–95.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Ho KT, Reveille JD. The clinical relevance of autoantibodies in scleroderma. Arthritis Res Ther. 2003;5:80–93.

    CAS  PubMed  Google Scholar 

  10. Hamaguchi Y. Autoantibody profiles in systemic sclerosis: predictive value for clinical evaluation and prognosis. J Dermatol. 2010;37:42–53.

    Article  CAS  PubMed  Google Scholar 

  11. Reveille JD, Solomon DH. Evidence-based guidelines for the use of immunologic tests: anticentromere, Scl-70, and nucleolar antibodies. Arthritis Rheum. 2003;49:399–412.

    Article  PubMed  Google Scholar 

  12. Moroi Y, Peebles C, Fritzler MJ, et al. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci U S A. 1980;77:1627–31.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Earnshaw WC, Machlin PS, Bordwell BJ, et al. Analysis of anticentromere autoantibodies using cloned autoantigen CENP-B. Proc Natl Acad Sci U S A. 1987;84:4979–83.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Masumoto H, Masukata H, Muro Y, et al. A human centromere antigen (CENP-B) interacts with a short specific sequence in alphoid DNA, a human centromeric satellite. J Cell Biol. 1989;109:1963–73.

    Article  CAS  PubMed  Google Scholar 

  15. Rothfield N, Whitaker D, Bordwell B, et al. Detection of anticentromere antibodies using cloned autoantigen CENP-B. Arthritis Rheum. 1987;30:1416–9.

    Article  CAS  PubMed  Google Scholar 

  16. Tan EM, Smolen JS, McDougal JS, 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.

    Article  CAS  PubMed  Google Scholar 

  17. Makinen D, Fritzler M, Davis P, et al. Anticentromere antibodies in primary biliary cirrhosis. Arthritis Rheum. 1983;26:914–7.

    Article  CAS  PubMed  Google Scholar 

  18. Lee SL, Tsay GJ, Tsai RT. Anticentromere antibodies in subjects with no apparent connective tissue disease. Ann Rheum Dis. 1993;52:586–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Caramaschi P, Biasi D, Manzo T, et al. Anticentromere antibody – clinical associations. A study of 44 patients. Rheumatol Int. 1995;14:253–5.

    Article  CAS  PubMed  Google Scholar 

  20. McNeilage LJ, Youngchaiyud U, Whittingham S. Racial differences in antinuclear antibody patterns and clinical manifestations of scleroderma. Arthritis Rheum. 1989;32:54–60.

    Article  CAS  PubMed  Google Scholar 

  21. Reveille JD, Fischbach M, McNearney T, et al. Systemic sclerosis in 3 US ethnic groups: a comparison of clinical, sociodemographic, serologic, and immunogenetic determinants. Semin Arthritis Rheum. 2001;30:332–46.

    Article  CAS  PubMed  Google Scholar 

  22. McHugh NJ, Whyte J, Artlett C, et al. Anti-centromere antibodies (ACA) in systemic sclerosis patients and their relatives: a serological and HLA study. Clin Exp Immunol. 1994;96:267–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Genth E, Mierau R, Genetzky P, et al. Immunogenetic associations of scleroderma-related antinuclear antibodies. Arthritis Rheum. 1990;33:657–65.

    Article  CAS  PubMed  Google Scholar 

  24. Kallenberg CG, Wouda AA, Hoet MH, et al. Development of connective tissue disease in patients presenting with Raynaud’s phenomenon: a six year follow up with emphasis on the predictive value of antinuclear antibodies as detected by immunoblotting. Ann Rheum Dis. 1988;47:634–41.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Tan EM, Rodnan GP, Garcia I, et al. Diversity of antinuclear antibodies in progressive systemic sclerosis. Anti-centromere antibody and its relationship to CREST syndrome. Arthritis Rheum. 1980;23:617–25.

    Article  CAS  PubMed  Google Scholar 

  26. Mitri GM, Lucas M, Fertig N, et al. A comparison between anti-Th/To- and anticentromere antibody-positive systemic sclerosis patients with limited cutaneous involvement. Arthritis Rheum. 2003;48:203–9.

    Article  PubMed  Google Scholar 

  27. Ferri C, Valentini G, Cozzi F, et al. Systemic sclerosis: demographic, clinical, and serologic features and survival in 1,012 Italian patients. Medicine (Baltimore). 2002;81:139–53.

    Article  Google Scholar 

  28. Hesselstrand R, Scheja A, Shen GQ, et al. The association of antinuclear antibodies with organ involvement and survival in systemic sclerosis. Rheumatology (Oxford). 2003;42:534–40.

    Article  CAS  Google Scholar 

  29. Tramposch HD, Smith CD, Senecal JL, et al. A long-term longitudinal study of anticentromere antibodies. Arthritis Rheum. 1984;27:121–4.

    Article  CAS  PubMed  Google Scholar 

  30. Vazquez-Abad D, Russell CA, Cusick SM, et al. Longitudinal study of anticentromere and antitopoisomerase-I isotypes. Clin Immunol Immunopathol. 1995;74:257–70.

    Article  CAS  PubMed  Google Scholar 

  31. Scussel-Lonzetti L, Joyal F, Raynauld JP, et al. Predicting mortality in systemic sclerosis: analysis of a cohort of 309 French Canadian patients with emphasis on features at diagnosis as predictive factors for survival. Medicine (Baltimore). 2002;81:154–67.

    Article  Google Scholar 

  32. Douvas AS, Achten M, Tan EM. Identification of a nuclear protein (Scl-70) as a unique target of human antinuclear antibodies in scleroderma. J Biol Chem. 1979;254:10514–22.

    CAS  PubMed  Google Scholar 

  33. Shero JH, Bordwell B, Rothfield NF, et al. High titers of autoantibodies to topoisomerase I (Scl-70) in sera from scleroderma patients. Science. 1986;231:737–40.

    Article  CAS  PubMed  Google Scholar 

  34. Reveille JD, Durban E, MacLeod-St Clair MJ, et al. Association of amino acid sequences in the HLA-DQB1 first domain with antitopoisomerase I autoantibody response in scleroderma (progressive systemic sclerosis). J Clin Invest. 1992;90:973–80.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Kuwana M, Kaburaki J, Okano Y, et al. The HLA-DR and DQ genes control the autoimmune response to DNA topoisomerase I in systemic sclerosis (scleroderma). J Clin Invest. 1993;92:1296–301.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Dick T, Mierau R, Bartz-Bazzanella P, et al. Coexistence of antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis. Ann Rheum Dis. 2002;61:121–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. 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.

    Article  CAS  PubMed  Google Scholar 

  38. Walker UA, Tyndall A, Czirjak L, et al. Clinical risk assessment of organ manifestations in systemic sclerosis: a report from the EULAR scleroderma trials and research group database. Ann Rheum Dis. 2007;66:754–63.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  39. Silver RM, Miller KS, Kinsella MB, et al. Evaluation and management of scleroderma lung disease using bronchoalveolar lavage. Am J Med. 1990;88:470–6.

    Article  CAS  PubMed  Google Scholar 

  40. Behr J, Vogelmeier C, Beinert T, et al. Bronchoalveolar lavage for evaluation and management of scleroderma disease of the lung. Am J Respir Crit Care Med. 1996;154:400–6.

    Article  CAS  PubMed  Google Scholar 

  41. Witt C, Borges AC, John M, et al. Pulmonary involvement in diffuse cutaneous systemic sclerosis: broncheoalveolar fluid granulocytosis predicts progression of fibrosing alveolitis. Ann Rheum Dis. 1999;58:635–40.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  42. Goh NS, Veeraraghavan S, Desai SR, et al. Bronchoalveolar lavage cellular profiles in patients with systemic sclerosis-associated interstitial lung disease are not predictive of disease progression. Arthritis Rheum. 2007;56:2005–12.

    Article  PubMed  Google Scholar 

  43. Wells AU, Hansell DM, Rubens MB, et al. Fibrosing alveolitis in systemic sclerosis: indices of lung function in relation to extent of disease on computed tomography. Arthritis Rheum. 1997;40:1229–36.

    CAS  PubMed  Google Scholar 

  44. Codullo V, Cavazzana I, Bonino C, et al. Serologic profile and mortality rates of scleroderma renal crisis in Italy. J Rheumatol. 2009;36:1464–9.

    Article  PubMed  Google Scholar 

  45. Weiner ES, Earnshaw WC, Senecal JL, et al. Clinical associations of anticentromere antibodies and antibodies to topoisomerase I. A study of 355 patients. Arthritis Rheum. 1988;31:378–85.

    Article  CAS  PubMed  Google Scholar 

  46. Rothfield N, Kurtzman S, Vazques-Abad D, et al. Association of anti-topoisomerase I with cancer. Arthritis Rheum. 1992;35:724.

    Article  CAS  PubMed  Google Scholar 

  47. Derk CT, Sakkas LI, Rasheed M, et al. Autoantibodies in patients with systemic sclerosis and cancer: a case-control study. J Rheumatol. 2003;30:1994–6.

    CAS  PubMed  Google Scholar 

  48. Higuchi M, Horiuchi T, Ishibashi N, et al. Anticentromere antibody as a risk factor for cancer in patients with systemic sclerosis. Clin Rheumatol. 2000;19:123–6.

    Article  CAS  PubMed  Google Scholar 

  49. Henry PA, Atamas SP, Yurovsky VV, et al. Diversity and plasticity of the anti-DNA topoisomerase I autoantibody response in scleroderma. Arthritis Rheum. 2000;43:2733–42.

    Article  CAS  PubMed  Google Scholar 

  50. Kuwana M, Kaburaki J, Mimori T, et al. Longitudinal analysis of autoantibody response to topoisomerase I in systemic sclerosis. Arthritis Rheum. 2000;43:1074–84.

    Article  CAS  PubMed  Google Scholar 

  51. Sato S, Hamaguchi Y, Hasegawa M, et al. Clinical significance of anti-topoisomerase I antibody levels determined by ELISA in systemic sclerosis. Rheumatology (Oxford). 2001;40:1135–40.

    Article  CAS  Google Scholar 

  52. Henault J, Robitaille G, Senecal JL, et al. DNA topoisomerase I binding to fibroblasts induces monocyte adhesion and activation in the presence of anti-topoisomerase I autoantibodies from systemic sclerosis patients. Arthritis Rheum. 2006;54:963–73.

    Article  CAS  PubMed  Google Scholar 

  53. Arcand J, Robitaille G, Koenig M, et al. The autoantigen DNA topoisomerase I interacts with chemokine receptor 7 and exerts cytokine-like effects on dermal fibroblasts. Arthritis Rheum. 2012;64:826–34.

    Article  CAS  PubMed  Google Scholar 

  54. Arcand J, Robitaille G, Koenig M, et al. Heparin inhibits the interaction of DNA topoisomerase I/anti-topoisomerase I immune complexes with heparan sulfate on dermal fibroblasts. Arthritis Rheum. 2012;64:1632–41.

    Article  CAS  PubMed  Google Scholar 

  55. Kuwana M, Kaburaki J, Mimori T, et al. Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis. J Clin Invest. 1993;91:1399–404.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  56. Okano Y, Steen VD, Medsger Jr TA. Autoantibody reactive with RNA polymerase III in systemic sclerosis. Ann Intern Med. 1993;119:1005–13.

    Article  CAS  PubMed  Google Scholar 

  57. Satoh M, Ajmani AK, Ogasawara T, et al. Autoantibodies to RNA polymerase II are common in systemic lupus erythematosus and overlap syndrome. Specific recognition of the phosphorylated (IIO) form by a subset of human sera. J Clin Invest. 1994;94:1981–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  58. Harvey GR, Rands AL, McHugh NJ. Anti-RNA polymerase antibodies in systemic sclerosis (SSc): association with anti-topoisomerase I antibodies and identification of autoreactive subunits of RNA polymerase II. Clin Exp Immunol. 1996;105:468–74.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Kuwana M, Okano Y, Pandey JP, et al. Enzyme-linked immunosorbent assay for detection of anti-RNA polymerase III antibody: analytical accuracy and clinical associations in systemic sclerosis. Arthritis Rheum. 2005;52:2425–32.

    Article  CAS  PubMed  Google Scholar 

  60. Satoh T, Ishikawa O, Ihn H, et al. Clinical usefulness of anti-RNA polymerase III antibody measurement by enzyme-linked immunosorbent assay. Rheumatology (Oxford). 2009;48:1570–4.

    Article  CAS  Google Scholar 

  61. Falkner D, Wilson J, Fertig N, et al. Studies of HLA-DR and DQ alleles in systemic sclerosis patients with autoantibodies to RNA polymerases and U3-RNP (fibrillarin). J Rheumatol. 2000;27:1196–202.

    CAS  PubMed  Google Scholar 

  62. Sobanski V, Dauchet L, Lefevre G, et al. Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: New data from a French cohort and a systematic review and meta-analysis. Arthritis Rheumatol. 2014;66:407–17.

    Article  CAS  PubMed  Google Scholar 

  63. Meyer OC, Fertig N, Lucas M, et al. Disease subsets, antinuclear antibody profile, and clinical features in 127 French and 247 US adult patients with systemic sclerosis. J Rheumatol. 2007;34:104–9.

    PubMed  Google Scholar 

  64. Airo P, Ceribelli A, Cavazzana I, et al. Malignancies in Italian patients with systemic sclerosis positive for anti-RNA polymerase III antibodies. J Rheumatol. 2011;38:1329–34.

    Article  CAS  PubMed  Google Scholar 

  65. Nikpour M, Hissaria P, Byron J, et al. Prevalence, correlates and clinical usefulness of antibodies to RNA polymerase III in systemic sclerosis: a cross-sectional analysis of data from an Australian cohort. Arthritis Res Ther. 2011;13:R211.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Hamaguchi Y, Kodera M, Matsushita T, et al. Clinical and immunologic predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III autoantibodies. Arthritis Rheumatol. 2015;67:1045–52.

    Article  CAS  PubMed  Google Scholar 

  67. Shah AA, Rosen A, Hummers L, et al. Close temporal relationship between onset of cancer and scleroderma in patients with RNA polymerase I/III antibodies. Arthritis Rheum. 2010;62:2787–95.

    Article  PubMed Central  PubMed  Google Scholar 

  68. Shah AA, Hummers LK, Casciola-Rosen L, et al. Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma. Arthritis Rheumatol. 2015;67:1053–61.

    Article  CAS  PubMed  Google Scholar 

  69. Joseph CG, Darrah E, Shah AA, et al. Association of the autoimmune disease scleroderma with an immunologic response to cancer. Science. 2014;343:152–7.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Steen VD, Medsger Jr TA. Long-term outcomes of scleroderma renal crisis. Ann Intern Med. 2000;133:600–3.

    Article  CAS  PubMed  Google Scholar 

  71. Okano Y, Medsger Jr TA. Autoantibody to Th ribonucleoprotein (nucleolar 7-2 RNA protein particle) in patients with systemic sclerosis. Arthritis Rheum. 1990;33:1822–8.

    Article  CAS  PubMed  Google Scholar 

  72. Yamane K, Ihn H, Kubo M, et al. Antibodies to Th/To ribonucleoprotein in patients with localized scleroderma. Rheumatology (Oxford). 2001;40:683–6.

    Article  CAS  Google Scholar 

  73. Hashimoto C, Steitz JA. Sequential association of nucleolar 7-2 RNA with two different autoantigens. J Biol Chem. 1983;258:1379–82.

    CAS  PubMed  Google Scholar 

  74. Reddy R, Tan EM, Henning D, et al. Detection of a nucleolar 7-2 ribonucleoprotein and a cytoplasmic 8-2 ribonucleoprotein with autoantibodies from patients with scleroderma. J Biol Chem. 1983;258:1383–6.

    CAS  PubMed  Google Scholar 

  75. Falkner D, Wilson J, Medsger Jr TA, et al. HLA and clinical associations in systemic sclerosis patients with anti-Th/To antibodies. Arthritis Rheum. 1998;41:74–80.

    Article  CAS  PubMed  Google Scholar 

  76. Kuwana M, Kimura K, Hirakata M, et al. Differences in autoantibody response to Th/To between systemic sclerosis and other autoimmune diseases. Ann Rheum Dis. 2002;61:842–6.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Cepeda EJ, Reveille JD. Autoantibodies in systemic sclerosis and fibrosing syndromes: clinical indications and relevance. Curr Opin Rheumatol. 2004;16:723–32.

    Article  CAS  PubMed  Google Scholar 

  78. Van Eenennaam H, Vogelzangs JH, Bisschops L, et al. Autoantibodies against small nucleolar ribonucleoprotein complexes and their clinical associations. Clin Exp Immunol. 2002;130:532–40.

    Article  PubMed  Google Scholar 

  79. Lischwe MA, Ochs RL, Reddy R, et al. Purification and partial characterization of a nucleolar scleroderma antigen (Mr = 34,000; pI, 8.5) rich in NG, NG-dimethylarginine. J Biol Chem. 1985;260:14304–10.

    CAS  PubMed  Google Scholar 

  80. Tormey VJ, Bunn CC, Denton CP, et al. Anti-fibrillarin antibodies in systemic sclerosis. Rheumatology (Oxford). 2001;40:1157–62.

    Article  CAS  Google Scholar 

  81. Arnett FC, Reveille JD, Goldstein R, et al. Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis. Arthritis Rheum. 1996;39:1151–60.

    Article  CAS  PubMed  Google Scholar 

  82. Sharif R, Fritzler MJ, Mayes MD, et al. Anti-fibrillarin antibody in African American patients with systemic sclerosis: immunogenetics, clinical features, and survival analysis. J Rheumatol. 2011;38:1622–30.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  83. Jacobsen S, Halberg P, Ullman S, et al. Clinical features and serum antinuclear antibodies in 230 Danish patients with systemic sclerosis. Br J Rheumatol. 1998;37:39–45.

    Article  CAS  PubMed  Google Scholar 

  84. Aggarwal R, Lucas M, Fertig N, et al. Anti-U3 RNP autoantibodies in systemic sclerosis. Arthritis Rheum. 2009;60:1112–8.

    Article  PubMed  Google Scholar 

  85. Gunduz OH, Fertig N, Lucas M, et al. Systemic sclerosis with renal crisis and pulmonary hypertension: a report of eleven cases. Arthritis Rheum. 2001;44:1663–6.

    Article  CAS  PubMed  Google Scholar 

  86. Nishimagi E, Tochimoto A, Kawaguchi Y, et al. Characteristics of patients with early systemic sclerosis and severe gastrointestinal tract involvement. J Rheumatol. 2007;34:2050–5.

    PubMed  Google Scholar 

  87. Rodriguez-Sanchez JL, Gelpi C, Juarez C, et al. Anti-NOR 90. A new autoantibody in scleroderma that recognizes a 90-kDa component of the nucleolus-organizing region of chromatin. J Immunol. 1987;139:2579–84.

    CAS  PubMed  Google Scholar 

  88. Chan EK, Imai H, Hamel JC, et al. Human autoantibody to RNA polymerase I transcription factor hUBF. Molecular identity of nucleolus organizer region autoantigen NOR-90 and ribosomal RNA transcription upstream binding factor. J Exp Med. 1991;174:1239–44.

    Article  CAS  PubMed  Google Scholar 

  89. Imai H, Ochs RL, Kiyosawa K, et al. Nucleolar antigens and autoantibodies in hepatocellular carcinoma and other malignancies. Am J Pathol. 1992;140:859–70.

    PubMed Central  CAS  PubMed  Google Scholar 

  90. Dagher JH, Scheer U, Voit R, et al. Autoantibodies to NOR 90/hUBF: longterm clinical and serological followup in a patient with limited systemic sclerosis suggests an antigen driven immune response. J Rheumatol. 2002;29:1543–7.

    PubMed  Google Scholar 

  91. Fujii T, Mimori T, Akizuki M. Detection of autoantibodies to nucleolar transcription factor NOR 90/hUBF in sera of patients with rheumatic diseases, by recombinant autoantigen-based assays. Arthritis Rheum. 1996;39:1313–8.

    Article  CAS  PubMed  Google Scholar 

  92. Dick T, Mierau R, Sternfeld R, et al. Clinical relevance and HLA association of autoantibodies against the nucleolus organizer region (NOR-90). J Rheumatol. 1995;22:67–72.

    CAS  PubMed  Google Scholar 

  93. Wassarman KM, Steitz JA. The low-abundance U11 and U12 small nuclear ribonucleoproteins (snRNPs) interact to form a two-snRNP complex. Mol Cell Biol. 1992;12:1276–85.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  94. Fertig N, Domsic RT, Rodriguez-Reyna T, et al. Anti-U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis Rheum. 2009;61:958–65.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  95. Burdt MA, Hoffman RW, Deutscher SL, et al. Long-term outcome in mixed connective tissue disease: longitudinal clinical and serologic findings. Arthritis Rheum. 1999;42:899–909.

    Article  CAS  PubMed  Google Scholar 

  96. Lundberg I, Hedfors E. Clinical course of patients with anti-RNP antibodies. A prospective study of 32 patients. J Rheumatol. 1991;18:1511–9.

    CAS  PubMed  Google Scholar 

  97. Ricken D. Progressive scleroderma and dermatomyositis. Verh Dtsch Ges Inn Med. 1977;83:751–6.

    CAS  PubMed  Google Scholar 

  98. Brouwer R, Vree Egberts WT, Hengstman GJ, et al. Autoantibodies directed to novel components of the PM/Scl complex, the human exosome. Arthritis Res. 2002;4:134–8.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  99. Reichlin M, Maddison PJ, Targoff I, et al. Antibodies to a nuclear/nucleolar antigen in patients with polymyositis overlap syndromes. J Clin Immunol. 1984;4:40–4.

    Article  CAS  PubMed  Google Scholar 

  100. Marguerie C, Bunn CC, Copier J, et al. The clinical and immunogenetic features of patients with autoantibodies to the nucleolar antigen PM-Scl. Medicine (Baltimore). 1992;71:327–36.

    Article  CAS  Google Scholar 

  101. Mimori T, Akizuki M, Yamagata H, et al. Characterization of a high molecular weight acidic nuclear protein recognized by autoantibodies in sera from patients with polymyositis-scleroderma overlap. J Clin Invest. 1981;68:611–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  102. Takeda Y, Dynan WS. Autoantibodies against DNA double-strand break repair proteins. Front Biosci. 2001;6:D1412–22.

    Article  CAS  PubMed  Google Scholar 

  103. Franceschini F, Cavazzana I, Generali D, et al. Anti-Ku antibodies in connective tissue diseases: clinical and serological evaluation of 14 patients. J Rheumatol. 2002;29:1393–7.

    PubMed  Google Scholar 

  104. Rozman B, Cucnik S, Sodin-Semrl S, et al. Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study. Ann Rheum Dis. 2008;67:1282–6.

    Article  CAS  PubMed  Google Scholar 

  105. Jha S, Dutta A. RVB1/RVB2: running rings around molecular biology. Mol Cell. 2009;34:521–33.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank Ms. Masako Matsubara, Yuko Yamada, and Tomoko Hayashi for technical assistance.

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  1. Department of Dermatology, Faculty of Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, 13-1 Takaramachi, Kanazawa, Ishikawa, 920-8641, Japan

    Yasuhito Hamaguchi

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  1. Yasuhito Hamaguchi
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Correspondence to Yasuhito Hamaguchi .

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Editors and Affiliations

  1. Department of Dermatology, Kanazawa University, Kanazawa, Ishikawa, Japan

    Kazuhiko Takehara

  2. Department of Dermatology, University of Tsukuba, Tsukuba, Ibaraki, Japan

    Manabu Fujimoto

  3. Department of Allergy and Rheumatology, Nippon Medical School, Tokyo, Tokyo, Japan

    Masataka Kuwana

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Hamaguchi, Y. (2016). Autoantibodies in Systemic Sclerosis. In: Takehara, K., Fujimoto, M., Kuwana, M. (eds) Systemic Sclerosis. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55708-1_14

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