Autoantibodies in Sjögren’s Syndrome

  • J. B. Harley


Antinuclear antibodies, rheumatoid factor and precipitating autoantibodies were first reported in Sjögren’s syndrome almost simultaneously over 25 years ago (Jones 1958; Weissman 1958; Heaton 1959). These findings were quickly exploited by investigators in Glasgow and Bethesda working separately and together. The high prevalence of rheumatoid factor in Sjögren’s syndrome was established by Bunim and colleagues (Bloch et al. 1960; Bunim 1961) and is considered elsewhere (see chapter on rheumatoid factor by Robert Fox and Dennis Carson in this volume).


Systemic Lupus Erythematosus Rheumatoid Factor Primary Biliary Cirrhosis Congenital Heart Block Subacute Cutaneous Lupus Erythematosus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Alexander EL, Hirsch TJ, Arnett FC, Provost TT, Stevens MB (1982) Ro(SSA) and La(SSB) antibodies in the clinical spectrum of Sjögren’s syndrome. J Rheumatol 9: 239–246PubMedGoogle Scholar
  2. Alexander EL, Arnett FC, Provost TT, Stevens MB (1983) Sjögren’s syndrome: Association of antiRo(SS-A) antibodies with vasculitis, hematologic abnormalities, and serologic hyperreactivity. Ann Intern Med 98: 155–159Google Scholar
  3. Aiken JK (1932) Congenital heart block. Lancet ii: 1375–1379Google Scholar
  4. Akizuki M, Boehm-Truitt MJ, Kassan SS, Steinberg AD, Chused TM (1977 a) Purification of an acidic nuclear protein antigen and demonstration of its antibodies in subsets of patients with sicca syndrome. J Immunol 119: 932–938Google Scholar
  5. Akizuki M, Powers R, Holman HR (1977 b) A soluble acidic protein of the cell nucleus which reacts with serum from patients with systemic lupus erythematosus and Sjögren’s syndrome. J Clin Invest 59: 264–272Google Scholar
  6. Alspaugh M, Maddison PJ (1979) Resulution of the identity of certain antigen-antibody systems in systemic lupus erythematosus and Sjögren’s syndrome: an interlaboratory collaboration. Arthritis Rheum 22: 796–798PubMedCrossRefGoogle Scholar
  7. Alspaugh MA, Tan EM (1975) Antibodies to cellular antigens in Sjögren’s syndrome. J Clin Invest 55: 1067–1073PubMedCrossRefGoogle Scholar
  8. Anderson LG, Tarpley TM, Talal N, Cummings NA, Wolf RO, Schall GL (1973) Cellular-versushumoral autoimmune responses to salivary gland in Sjögren’s syndrome. Clin Exp Immunol 13: 335–342PubMedGoogle Scholar
  9. Anderson JR, Gray KG, Beck JS, Kinnear WF (1961) Precipitating autoantibodies in Sjögren’s disease. Lancet ii: 456–460Google Scholar
  10. Aylward RD (1928) Congenital heart block. Br Med J is 943Google Scholar
  11. Bernstein RM, Bunn CC, Hughes GRV, Francoeur AM, Mathews MB (1984) Cellular protein and RNA antigens in autoimmune disease. Mol. Biol. Med. 2: 105–120Google Scholar
  12. Bernstein RM, Hobbs RN, Lea DJ, Ward DJ, Hughes GRV (1985) Patterns of antihistone antibody specificity in systemic rheumatic disease. I. Systemic lupus erythematosus, mixed connective tissue disease, primary sicca syndrome, and rheumatoid arthritis with vasculitis. Arthritis Rheum 28: 285–293Google Scholar
  13. Bertram U, Halberg P (1964) A specific antibody against the epithelium of the salivary ducts in sera from patients with Sjögren’s syndrome. Acta Allerg (Kbh.) 19: 458–466Google Scholar
  14. Biore G, Menard H-A (1985) Clinical significance of anti-SSA(Ro) in rheumatoid arthritis. Arthritis Rheum 28: S47Google Scholar
  15. Bloch KJ, Bunim JJ, Wohl MJ, Zvaifler NJ (1960 a) Unusual occurrence of multiple tissue component antibodies in Sjögren’s syndrome. Trans Ass Amer Phys 73: 166–175Google Scholar
  16. Bloch KJ, Wohl MJ, Ship II, Oglesby RB, Bunim JJ (1960b) Sjögren’s syndrome. I. Serologic reactions in patients with Sjögren’s syndrome with and without rheumatoid arthritis. Arthritis Rheum 3: 287–297Google Scholar
  17. Bloch KJ, Buchanan WW, Wohl MJ, Bunim JJ (1965) Sjögren’s syndrome. A clinical pathological, and serological study of sixty-two cases. Medicine (Baltimore) 44: 187–231Google Scholar
  18. Bunim JJ (1961) Heberden oration. A broader spectrum of Sjögren’s syndrome and its pathogenic implications. Ann Rheum Dis 20: 1–10PubMedCrossRefGoogle Scholar
  19. Bunim JJ, Buchanan WW, Wertlake PT, Sokolof L, Bloch KJ, Beck JS, Alepa FP (1964) Clinical staff conference. Clinical, pathologic and serologic studies in Sjögren’s syndrome. Ann Intern Med 61: 509–530Google Scholar
  20. Chambers JC, Keene JD (1985) Isolation and analysis of cDNA clones expressing human lupus La antigen. Proc Natl Acad Sci USA 82: 2115–2119PubMedCrossRefGoogle Scholar
  21. Clark GM, Reichlin M, Tomasi TB (1968) Characterization of soluble cytoplasmic antigen reactive with sera from patients with systemic lupus erythematosus. J Immunol 102: 117–122Google Scholar
  22. Charron DJ, Lotteau V, Tunnel P (1984) Hybrid HLA-DC antigens provide molecular evidence for gene complementation. Nature 305: 813–815Google Scholar
  23. Charron DJ, Lotteau V, Tunnel P (1985) Hybrid HLA-DC/DS antigens: Molecular evidence for gene trans-complementation. In “histocompatibility Testing 1984” (ED Albert, MP Baur, M Mayr, eds). Heidelberg: Springer Verlag.Google Scholar
  24. Deng JS, Takasaki Y, Tan EM (1981) Nonhistone nuclear antigens reactive with autoantibodies. Immunofluorescent studies of distribution in synchronized cells. J Cell Biol 91: 654–660Google Scholar
  25. Deng JS, Santheimer RD, Gilliam JN (1985) Expression of Ro/SS-A antigen in human skin and heart. J Invest Denn 85: 412–416CrossRefGoogle Scholar
  26. Dorf ME (1978) Complementation of H-2-linked genes controlling immune responsiveness. Springer Semin. Immunopathol 1: 171–206Google Scholar
  27. Dorf ME, Benacerraf B (1975) Complementation of the H-2 linked Ir genes in the mouse. Proc Natl Acad Sci USA 72: 3671–3075PubMedCrossRefGoogle Scholar
  28. Eisenberg RA (1985) Association of the Ro and La antigenic determinant. Immunodiffusion analysis of human spleen extract. J Immunol 135: 1707–1713PubMedGoogle Scholar
  29. Feltkamp TEW, van Rossum AL (1983) Antibodies to salivary duct cells, and other autoantibodies, in patients with Sjögren’s syndrome and other idiopathic autoimmune diseases. Clin Exp ImmunoI 3: 1–16Google Scholar
  30. Figueroa F, Klein J (1986) The evaluation of MHC class II genes. Immunol Today 7; 78–81.CrossRefGoogle Scholar
  31. Forman MS, Nakamura M, Mimori T, Gelpi C, Hardin JA (1985) Detection of antibodies to small nuclear ribonucleoproteins and small cytoplasmic ribonucleoproteins using unlabeled cell extracts. Arthritis Rheum 28: 1356–1361PubMedCrossRefGoogle Scholar
  32. Francoeur AM, Chan EKL, Garrets JI, Mathews MB (1985) Characterization and purification of lupus antigen La, an RNA binding protein. Molec Cellular Biol 5: 586–590Google Scholar
  33. Gaither KK, Harley JB (1985) Affinity purification and immunoassay of anti-Ro/SSA. Protides Biol Fluids 33: 343–346Google Scholar
  34. Giles RC, Capra JD (1985) Biochemistry of MHC class II molecules. Tissues Antigens 26: 57–68Google Scholar
  35. Giles RC, DeMars RC, Chang C, Capra JD (1985) Allelic polymorphism and transassociation of molecules encoded by the HLA-DQ subregion. Proc Natl Acad Sci (USA) 82: 1776–1780CrossRefGoogle Scholar
  36. Graus F, Cordon-Cardo C, Bonfa E, Elkon KB (1985) Immunohistochemical localization of La nuclear antigen in brain. Selective concentration of the La protein in neuronal nucleoli. J Neuroimmunology 9: 307–319Google Scholar
  37. Gumpel JM, Hobbs JR (1970) Serum immune globulins in Sjögren’s syndrome. Ann Rheum Dis 29: 681–683PubMedCrossRefGoogle Scholar
  38. Halberg P, Bertram U, Soberg M, Nerup J (1965) Organ antibodies in disseminated lupus erythematosus. Acta Med Scand 178: 291–299PubMedCrossRefGoogle Scholar
  39. Habets WJ, den Brok JH, Boerbooms AMT, Van de Putte LBA, van Venrooij WJ (1983) Characterization of the SS-B(La) antigen in adenovirus-infected and uninfected HeLa cells. Europ J Mol Biol 2: 1625–1631Google Scholar
  40. Harley JB (1985) Autoantibodies in Sjögren’s syndrome: comparison of autoantibody determination methods show that antinuclear antibody and rheumatoid factor are associated with Ro/SSA precipitin formation. Protides Biol Fluids 33: 343–346Google Scholar
  41. Harley JB, Yamagata H, Reichlin M (1984) Anti-La/SSB antibody is present in some normal sera and is coincident with anti-Ro/SSA precipitins in systemic lupus erythematosus. J Rheumatol 11: 309–314PubMedGoogle Scholar
  42. Harley JB, Kaine JL, Fox OF, Reichlin M, Graber B (1985 a) Ro/SSA antibody and antigen in congenital complete heart block. Arthritis Rheum 28: 1321–1325Google Scholar
  43. Harley JB, Rosario MO, Tamagata H, Fox OF, Koren E ( 1985 b) Immunologic and structural studies of the lupus/Sjögren’s syndrome autoantigen, La/SSB, with a monoclonal antibody. J Clin Invest 76: 801–806Google Scholar
  44. Harley JB, Alexander EL, Bias WB, Fox OF, Provost Ti’, Reichlin M, Yamagata M, Arnet FC (1986 a) Anti-Ro(SS-A) and anti-La(SS-B) in patients with Sjögren’s syndrome. Arthritis Rheum 29: 196–206Google Scholar
  45. Harley JB, Reichlin M, Arnett FC, Alexander EL, Bias WB, Provost TT (1986 b) Gene interaction at HLA-DQ enhances autoantibody production in primary Sjögren’s syndrome. Science 232: 1145–1147Google Scholar
  46. Harmon CE, Deng JS, Peebles CL, Tan EM (1984) The importance of tissue substrate in the SS-A/ Ro antigen-antibody system. Arthritis Rheum 27: 166–172PubMedCrossRefGoogle Scholar
  47. Heaton JM (1959) Sjögren’s syndrome and systemic lupus erythematosus. Brit Med J is 466–469Google Scholar
  48. Hendrick JP, Wolin S, Rinke J, Lerner MR, Steitz JA (1981) Ro small cytoplasmic ribonucleoproteins are a subclass of La ribonucleoproteins: further characterization of the Ro and La small ribonucleoproteins from uninfected mammalian cells. Mol Cell Biol 1: 1138–1149PubMedGoogle Scholar
  49. Hochberg MC, Boyd RE, Ahearn JM, Arnett FC, Bias WB, Provost TT, Stevens MB (1985) Systemic lupus erythematosus: a review of clinico-laboratory features and immunogenetic markers in 150 patients with emphasis on dermatographic subsets. Medicine (Baltimore) 64: 285–295Google Scholar
  50. Jelinek WR, Toomey TP, Leinwand L, Duncan CH, Biro PA, Chondary PV, Weissman SM, Rubin CM, Houck CM, Deininger PL, Schmidt CW (1980) Ubiquitous, interspersed repeated sequences in mammalian genomes. Proc Natl Acad Sci USA 77: 1398–1402PubMedCrossRefGoogle Scholar
  51. Jones BR (1958) Lacrimal and salivary precipitating antibodies. Lancet ii: 773–735Google Scholar
  52. Jordan SC, Sakai R, Tabak MA, Ettenger RB, Cohen AH, Fine RN (1985) Induction of neonatal renal tubular dysfunction by transplacentally acquired IgG from a mother with Sjögren’s syn-drome. J Pediat 107: 566–569PubMedCrossRefGoogle Scholar
  53. Kato N, Hoshino H, Harada F (1982) Nucleotide sequence of 4.5s RNA (C8 or hY5) from HeLa cells. Biochem Biophys Res Conunun 108: 363–370Google Scholar
  54. Kephart D, Hood A, Provost Ti’. Neonatal lupus: serologic findings. J Invest Derm 77: 331–333Google Scholar
  55. Kurilla MG, Keene JD (1983) The leader RNA of vesicular stomatitis virus is bound by a cellular protein reactive with anti-La lupus antibodies. Cell 34: 837–845PubMedCrossRefGoogle Scholar
  56. Kurki P, Helve T, Virtanen I (1983) Antibodies to cytoplasmic intermediate filaments in rheumatic diseases. J Rheumatol 10: 558–562PubMedGoogle Scholar
  57. Lerner MR, Andrews NC, Miller G, Steitz JA (1981 a) Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc Natl Acad Sci USA 78: 805–809Google Scholar
  58. Lerner MR, Boyle JA, Hardin JA, Steitz JA (1981 b) Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science 211: 400–402Google Scholar
  59. Litsky SE, Noonan JA, O’Connor WN, Cottrill CM, Mitchell B (1985) Maternal connective tissue disease and congenital heart block. Demonstration of immunoglobulin in cardiac tissue. N Engl J Med 312: 98–100Google Scholar
  60. Lumpkin LR, Hall J, Hogan JD, Tucker SB, Jordan RE (1985) Neonatal lupus erythematosus: a report of three cases associated with anti-Ro/SSA antibodies. Arch Dermato1121: 377–381Google Scholar
  61. MacSween RNM, Goudie RB, Anderson JR, Armstrong E, Murray MA, Mason DK, Jasani MK, Boyle JA, Buchanan WW, Williamson J (1967) Occurence of antibody to salivary duct epithelium in Sjögren’s disease, rheumatoid arthritis and other arthritides: a clinical and laboratory study. Ann Rheum Dis 26: 402–411PubMedCrossRefGoogle Scholar
  62. Maddison PJ, Reichlin M (1977) Quantitation of precipitating antibodies to certain soluble nuclear antigens in SLE: their contribution to hypergammaglobulinemia. Arthritis Rheum 20: 819–824PubMedCrossRefGoogle Scholar
  63. Maddison PJ, Provost TT, Reichlin M (1981) Serological findings in patients with “ANA-negative” systemic lupus erythematosus. Medicine (Baltimore) 60: 87–94Google Scholar
  64. Maddison PJ, Reichlin M (1979) Deposition of antibodies to a soluble cytoplasmic antigen in the kidneys of patients with systemic lupus erythematosus. Arthritis Rheum 22: 858–863PubMedCrossRefGoogle Scholar
  65. Maddison PJ, Skinner RP, Vlachoyiannopoulos P, Brennand DM, Hough D (1985) Antibodies to nRNP, Sm, Ro(SSA), and La(SSB) detected by ELISA: their specificity in connective tissue disease sera. Clin Exp Immunol 62: 337–345PubMedGoogle Scholar
  66. Madore Si, Wieben ED, Pederson T (1984) Eukaryotic small ribonucleoproteins: anti-La human autoantibodies react with U1 RNA-protein complexes. J Biol Chem 259: 1929–1933PubMedGoogle Scholar
  67. Mamula M, Fox OF, Harley JB (1985) Cross-reactivity of Ro/SSA and immunoglobulin G. Arthri-tis Rheum 28: S37Google Scholar
  68. Mathews MB, Francoeur AM (1982) Interaction between VA RNA and the lupus antigen La: formation of a ribonucleoprotein in vitro. Proc Natl Acad Sci USA 79: 6772–6776PubMedCrossRefGoogle Scholar
  69. Mattioli M, Reichlin M (1974) Heterogenity of RNA protein antigens reactive with sera of patients with systemic lupus erythematosus. Arthritis Rheum 17: 421–429PubMedCrossRefGoogle Scholar
  70. Miyachi K, Naito M, Maeno Y, Suzuki S, Hamamoto T, Sugiura M, Kasahava M, Torikai K, Umeda H (1983) Sialographic study in patients with and without antibodies to Sjögren’s syndrome A ( Ro ). J Rheumatol 10: 387–394Google Scholar
  71. Miyagawa S, Kitamura W, Yoshioka J, Sakamoto K (1981) Placental transfer of anticytoplasmic antibodies in annular crythema of newborns. Arch Dermatol 117: 569–572PubMedCrossRefGoogle Scholar
  72. Molina R, Provost TT, Alexander EL (1985) Two types of inflammatory vascular disease in Sjögren’s syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro(SS-A) and with hypocomplemantemia. Arthritis Rheum 28: 1251–1258Google Scholar
  73. Moore CL, Sharp PA (1984) Site-specific polyadenylation in a cell-free reaction. Cell 36: 581–591PubMedCrossRefGoogle Scholar
  74. Moutsopoulos HM, Skopouli FN, Sarras AK, Tsampoulos C, Mauridis AK, Constantopoulos SH, Maddison PJ (1985) Anti-Ro(SS-A) positive rheumatoid arthritis (RA): a clinico serological group of patients with high incidence of D-penicillamine side effects. Ann Rheum Dis 44: 215–219PubMedCrossRefGoogle Scholar
  75. Mumford P, J.00m GRW, Venables PJW, Maini RN (1985) IgG antibodies to SS-B(La), RNP/Sm and DNA are produced by PWM-stimulated normal human lymphocytes in culture. Rheumatol Int 5: 109–112Google Scholar
  76. Ouarma TB, Krueger JA, Holman HR (1982) Analysis of speckled fluorescent antinuclear antibody test antisera using electrofocused nuclear antigens. J Clin Invest 70: 296–303CrossRefGoogle Scholar
  77. Penner E, Reichlin M (1982) Primary biliary cirrhosis associated with Sjögren’s syndrome: evidence for circulating and tissue deposited Ro/anti-Ro immune complexes. Arthritis Rheum 25: 1250–1253PubMedCrossRefGoogle Scholar
  78. Pizer L, Deng JS, Sternberg R, Tan EM (1983) Characterization of a phosphoprotein associated with the SS-B/La nuclear antigen in adenovirus-infected and uninfected KB cells. Mol Cell Biol 7: 1235–1245Google Scholar
  79. Provost TT (1983) Neonatal lupus. Arch Dermatol 119: 619–622Google Scholar
  80. Provost TT, Arnett FC, Reichlin M (1983) Homozygous C2 Deficiency, lupus erythematosus, and anti-Ro(SS-A) antibodies. Arthritis Rheum 26: 1279–1282PubMedCrossRefGoogle Scholar
  81. Reichlin M (1979) Newly defined serologic systems in systemic lupus erythematosus and dermatomyositis. Inter J Derm 18: 602–607CrossRefGoogle Scholar
  82. Reinke J, Steitz JA (1982) Precursor molecules of both human 5S ribosomal RNA and transfer RNAs are bound by a cellular protein reactive with anti-La lupus antibodies. Cell 29: 149–159CrossRefGoogle Scholar
  83. Reddy R, Henning P, Tan EM, Busch H (1983) Identification of a La protein binding site in a RNA polymerase III transcript (4.51 RNA). J Biol Chem 258: 8352–8356PubMedGoogle Scholar
  84. Rosa MD, Gottlieb E, Lerner MR, Steitz JA (1981) Striking similarities are exhibited by two small Epstein-Barr virus-encloded ribonucleic acids and the adenovirus-associated ribonucleic acids VAI and VAIL Molec Cell Biol 1: 785–796Google Scholar
  85. Santheimer RD, Maddison PJ, Reichlin M, Jordon RE, Stasny P, Gillam JM (1982) Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 97: 664–671Google Scholar
  86. Scopelitis E, Biundo JJ (1984) Inconsistent staining of HEp-2 cells with anti-SS-A antibody. Arthritis Rheum 27: 1318–1320PubMedCrossRefGoogle Scholar
  87. Scott JS, Maddison PJ, Taylor PV, Esscher E, Scott O, Skinner RP (1982) Connective-tissue disease, antibodies to ribonucleoprotein and congenital heart block. N Engl J Med 309: 209–212CrossRefGoogle Scholar
  88. Stefano JE (1984) Purified lupus antigen La recognizes an oligouridylate stretch common to the 3’ termini of RNA polymerase III transcripts. Cell 36: 145–154PubMedCrossRefGoogle Scholar
  89. Teppo A-M (1981) Enzyme immunoassay of antibodies to Sjögren’s syndrome B antigen. Clin Chem 27: 1341–1345PubMedGoogle Scholar
  90. Venables PJW, Charles PJ, Buchanan RRC, Fi T, Munford PA, Schrieber L, Room GRW, Maini RN (1983 a) Quantitation and detection of isotypes of anti-SS-B antibodies by ELISA and Farr assays sing affinity purified antigens: an approach to the investigation of Sjögren’s syndrome and sytemic lupus erythematosus. Arthritis Rheum 26: 146–155Google Scholar
  91. Venables PJW, Smith PR, Maini RN (1983 b) Purification and characterization of the Sjögren’s syndrome A and B antigens. Clin Exp Immunol 54: 731–738Google Scholar
  92. Virji MA (1985) Circulating prostatic acid phosphatase-immunoglobulin complexes in Sjögren’s syndrome. Clin Chem Acta 151: 223–230CrossRefGoogle Scholar
  93. Weissmann G (1958) Sjögren’s syndrome. Review of the literature and report of a case with achalasia of the esophagus. Am J Med 24: 475–481PubMedCrossRefGoogle Scholar
  94. Wermuth DJ, Goeghegan WD, Jordan RE (1985) Anti-Ro/SSA antibodies. Association with a particulate (large speckled like thread) immunofluorescent nuclear staining pattern. Arch Dermatol 121: 335–338Google Scholar
  95. Whaley K, Chisholm DM, Goudie RB, Downie WW, Dizk WC, Boyle JA, Williamson J (1969) Salivary duct autoantibody in Sjögren’s syndrome: correlation with focal sialadenitis in the labial mucosa. Clin Exp Immunol 4: 273–282Google Scholar
  96. Whaley K, Webb J, McAvoy BA, Hughes GRV, Lee P, MacSween RNM, Buchanan WW (1973) Sjögren’s syndrome. 2. Clinical associations and immunological phonomena. Quart J Med (New series) 17: 513–548Google Scholar
  97. Whittingham S, McNeilage J, MacKay IR (1985) Primary Sjögren’s syndrome after infectious mononucleosis. Ann Intern Med 102: 490–493PubMedGoogle Scholar
  98. Wolin SL, Steitz JA (1983) Genes for two small cytoplasmic Ro RNAs are adjacent and appear to be single copy in the human genome. Cell 32: 735–744Google Scholar
  99. Wolin SL, Steitz JA (1984 a) The Ro small cytoplasmic ribonucleoproteins: identification of the antigenic protein and its binding on the Ro RNAs. Proc Natl Acad Sic USA 81: 1996–2000Google Scholar
  100. Wolin SL, Steitz JA (1984b) The Ro small cytoplasmic ribonucleoprotein particle: structures and clues to the pathogenesis of congenital heart block. Clin Res 32: 470 AGoogle Scholar
  101. Yamagata H, Harley JB, Reichlin M (1984) Molecular properties of the Ro/SSA antigen and ELISA for quantification of antibody. J Clin Invest 74: 625–633PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1987

Authors and Affiliations

  • J. B. Harley

There are no affiliations available

Personalised recommendations