Journal of Molecular Medicine

, Volume 82, Issue 7, pp 423–433 | Cite as

Autoantigens of the nuclear pore complex

  • P. Enarson
  • J. B. Rattner
  • Y. Ou
  • K. Miyachi
  • T. Horigome
  • M. J. FritzlerEmail author


The nuclear envelope (NE) is one of many intracellular targets of the autoimmune response in patients with autoimmune liver disease, systemic lupus erythematosus, and related conditions. In eukaryotic organisms the NE consists of five interconnected regions: an outer nuclear membrane (ONM) that is continuous with the endoplasmic reticulum, an intermembrane or perinuclear space, an inner nuclear membrane (INM) with a unique set of integral membrane proteins, the underlying nuclear lamina, and the pore domains that are regions where the ONM and INM come together. The pore domains are sites of regulated continuity between the cytoplasm and nucleus that are occupied by supramolecular structures, termed nuclear pore complexes (NPCs). Human autoantibodies identified to date bind to specific components in three of the five NE compartments. Autoantigen targets include the lamins A, B, and C of the nuclear lamina, gp210, p62 complex proteins, Nup153, and Tpr within the NPC, and LBR, MAN1, LAP1, and LAP2 that are integral proteins of the INM. Autoantibodies to these NE targets have been shown to be correlated with various autoimmune diseases such as primary biliary cirrhosis, other autoimmune liver diseases and systemic rheumatic diseases. Now that the proteome of the NE is more clearly defined, other autoantibodies to components in this cell compartment are likely to be defined.


Nuclear envelope Nuclear pore complex Autoantibodies Autoimmune diseases Antigens 



Nuclear envelope


Outer nuclear membrane


Inner nuclear membrane


Nuclear pore complex


Indirect immunofluorescence


Systemic lupus erythematosus


Primary biliary cirrhosis


Chronic fatigue syndrome



The authors extend appreciation to Meifeng Zhang for producing some of the illustrations, and to Drs. N. Pante and I. Macara for permission to use previously published graphics. This research was supported by the Canadian Institutes of Health Research (grant no. MOP 38034) and a grant from the Natural Sciences and Environment Research Council to J.B.R. M.J.F. holds the Arthritis Society Research Chair at the University of Calgary. P.E. was supported by an MD/PhD studentship from the Alberta Heritage Foundation for Medical Research, and Y.O. is supported by a CIHR/Ernst & Young Post-doctoral Award.


  1. 1.
    Rattner JB, Fritzler MJ (1996) Centriole and centrosome autoantibodies. In: Peter JB, Shoenfeld Y (eds) Autoantibodies. Elsevier, Amsterdam, pp 153–160Google Scholar
  2. 2.
    Gavanescu D, Vasquez ABAD, McCauley J, Senécal J-L, Doxsey S (1999) Centrosome proteins: a major class of autoantigens in scleroderma. J Clin Immunol 19:166–171CrossRefPubMedGoogle Scholar
  3. 3.
    Balczon R (1993) Autoantibodies as probes in cell and molecular biology. Proc Soc Exp Biol Med 204:138–154PubMedGoogle Scholar
  4. 4.
    Mu FT, Callaghan JM, Steele-Mortimer HS, Parton RG, Campbell PL, McCluskey J, Yeo JP, Tock EPC, Toh BH (1995) EEA1, an early endosomal protein. J Biol Chem 270:13503–13511CrossRefPubMedGoogle Scholar
  5. 5.
    Selak S, Schoenroth L, Senécal J-L, Fritzler MJ (1999) Early endosome antigen 1: an autoantigen associated with neurological diseases. J Investig Med 47:311–318Google Scholar
  6. 6.
    Kain R, Matsui K, Exner M, Binder S, Schaffner G, Sommer EM, Kerjaschki D (1995) A novel class of autoantigens of anti-neutrophil cytoplasmic antibodies in necrotizing and crescentic glomerulonephritis: the lysosomal membrane glycoprotein h-lamp-2 in neutrophil granulocytes and a related membrane protein in glomerular endothelial cells. J Exp Med 181:585–597PubMedGoogle Scholar
  7. 7.
    Chan EKL, Fritzler MJ (1998) Autoantibodies to Golgi apparatus antigens. In: Conrad K, Humbel R-L, Meurer M, Shoenfeld Y, Tan EM (eds) Pathogenic and diagnostic relevance of autoantibodies. Proceedings of the 4th Dresden Symposium on Autoantibodies. Pabst, Scottsdale, pp 85–100Google Scholar
  8. 8.
    Chan EKL, Fritzler MJ (1998) Golgins: coiled-coil-rich proteins associated with the Golgi complex. Electronic J Biotechnol 1:
  9. 9.
    Fritzler MJ, Manns MP (2002) Anti-mitochondrial antibodies. Clin Appl Immunol Rev 3:87–113CrossRefGoogle Scholar
  10. 10.
    Eystathioy T, Chan EKL, Yang Z, Takeuchi K, Mahler M, Luft LM, Zochodne DW, Fritzler MJ (2003) Clinical and serological associations of autoantibodies to a novel cytoplasmic autoantigen, GW182 and GW bodies. J Mol Med 81:811–818CrossRefPubMedGoogle Scholar
  11. 11.
    von Muhlen CA, Tan EM (1995) Autoantibodies in the diagnosis of systemic rheumatic disease. Semin Arthritis Rheum 24:323–358PubMedGoogle Scholar
  12. 12.
    Stinton LM, Eystathioy T, Selak S, Chan EKL, Fritzler MJ (2004) Autoantibodies to protein transport and messenger RNA processing pathways: endosomes, lysosomes, Golgi complex, proteasomes, assemblyosomes, exosomes and GW Bodies. Clin Immunol 110:30–44CrossRefPubMedGoogle Scholar
  13. 13.
    Konstantinov K, Foisner R, Byrd D, Liu F-T, Tsai W-M, Wiik A, Gerace L (1995) Integral membrane proteins associated with the nuclear lamina are novel autoimmune antigens of the nuclear envelope. Clin Immunol Immunopathol 74:89–99CrossRefPubMedGoogle Scholar
  14. 14.
    Lin F, Noyer CM, Ye Q, Courvalin JC, Worman HJ (1996) Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR. Hepatology 23:57–61CrossRefPubMedGoogle Scholar
  15. 15.
    Konstantinov K, Von Mikecz A, Buchwald D, Jones J, Gerace L, Tan EM (1996) Autoantibodies to nuclear envelope antigens in chronic fatigue syndrome. J Clin Invest 98:1888–1896PubMedGoogle Scholar
  16. 16.
    Lin F, Blake DL, Callebaut I, Skerjanc IS, Holmer L, McBurney MW, Paulin-Levasseur M, Worman HJ (2000) MAN1, an inner nuclear membrane protein that shares the LEM domain with lamina-associated polypeptide 2 and emerin. J Biol Chem 275:4840–4847CrossRefPubMedGoogle Scholar
  17. 17.
    Nesher G, Margalit R, Ashkenazi YJ (2001) Anti-nuclear envelope antibodies: Clinical associations. Semin Arthritis Rheum 30:313–320Google Scholar
  18. 18.
    Miyachi K, Hankins RW, Matsushima H, Kikuchi F, Inomata T, Horigome T, Shibata M, Onozuka Y, Ueno Y, Hashimoto E, Hayashi N, Shibuya A, Amaki S, Miyakawa H (2003) Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study. J Autoimmunol 20:247–254CrossRefGoogle Scholar
  19. 19.
    Czaja AJ, Norman GL (2003) Autoantibodies in the diagnosis and management of liver disease. J Clin Gastroenterol 37:315–329Google Scholar
  20. 20.
    Salina D, Bodoor K, Enarson P, Raharjo WH, Burke B (2001) Nuclear envelope dynamics. Biochem Cell Biol 79:533–542CrossRefPubMedGoogle Scholar
  21. 21.
    Konstantinov K (1996) Nuclear envelope protein autoantibodies. In: Peter JB, Shoenfeld Y (eds) Autoantibodies. Elsevier, Amsterdam, pp 561–566Google Scholar
  22. 22.
    Pante N, Aebi U (1994) Toward the molecular details of the nuclear pore complex. J Struct Biol 113:179–189CrossRefPubMedGoogle Scholar
  23. 23.
    Hinshaw JE, Carragher BO, Milligan RA (1992) Architecture and design of the nuclear pore complex. Cell 69:1133–1141PubMedGoogle Scholar
  24. 24.
    Akey CW, Radermacher M (1993) Architecture of the Xenopus nuclear pore complex revealed by three-dimensional cryo-electron microscopy. J Cell Biol 122:1–19PubMedGoogle Scholar
  25. 25.
    Pante N, Aebi U (1995) Exploring nuclear pore complex structure and function in molecular detail. J Cell Sci [Suppl] 19:1–11Google Scholar
  26. 26.
    Feldherr CM, Akin D (1997) The location of the transport gate in the nuclear pore complex. J Cell Sci 110:3065–3070PubMedGoogle Scholar
  27. 27.
    Bednenko J, Cingolani G, Gerace L (2003) Nucleocytoplasmic transport: navigating the channel. Traffic 4:127–135PubMedGoogle Scholar
  28. 28.
    Stoffler D, Fahrenkrog B, Aebi U (1999) The nuclear pore complex: from molecular architecture to functional dynamics. Curr Opin Cell Biol 11:391–401CrossRefPubMedGoogle Scholar
  29. 29.
    Pante N, Aebi U (1996) Toward the molecular dissection of protein import into nuclei. Curr Opin Cell Biol 8:397–406CrossRefPubMedGoogle Scholar
  30. 30.
    Kiseleva E, Goldberg MW, Daneholt B, Allen TD (1996) RNP export is mediated by structural reorganization of the nuclear pore basket. J Mol Biol 260:304–311CrossRefPubMedGoogle Scholar
  31. 31.
    Gerace L, Burke B (1988) Functional organization of the nuclear envelope. Annu Rev Cell Biol 4:335–374PubMedGoogle Scholar
  32. 32.
    Reichelt R, Holzenburg A, Buhle EL Jr, Jarnik M, Engel A, Aebi U (1990) Correlation between structure and mass distribution of the nuclear pore complex and of distinct pore complex components. J Cell Biol 110:883–894PubMedGoogle Scholar
  33. 33.
    Cronshaw JM, Krutchinsky AN, Zhang W, Chait BT, Matunis MJ (2002) Proteomic analysis of the mammalian nuclear pore complex. J Cell Biol 158:915–927CrossRefPubMedGoogle Scholar
  34. 34.
    Fahrenkrog B, Stoffler D, Aebi U (2001) Nuclear pore complex architecture and functional dynamics. Curr Top Microbiol Immunol 259:95–117PubMedGoogle Scholar
  35. 35.
    Rout MP, Aitchison JD (2000) Pore relations: nuclear pore complexes and nucleocytoplasmic exchange. Essays Biochem 36:75–88PubMedGoogle Scholar
  36. 36.
    Raharjo WH, Enarson P, Sullivan T, Stewart CL, Burke B (2001) Nuclear envelope defects associated with LMNA mutations cause dilated cardiomyopathy and Emery-Dreyfuss muscular dystrophy. J Cell Sci 114:4447–4457PubMedGoogle Scholar
  37. 37.
    Pante N, Kann M (2002) Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm. Mol Biol Cell 13:425–434CrossRefPubMedGoogle Scholar
  38. 38.
    Ribbeck K, Gorlich D (2001) Kinetic analysis of translocation through nuclear pore complexes. EMBO J 20:1320–1330PubMedGoogle Scholar
  39. 39.
    Jäggi RD, Franco-Obregón A, Ensslin K (2003) Quantitative topographical analysis of nuclear pore complex function using scanning force microscopy. Biophys J 85:4093–4098PubMedGoogle Scholar
  40. 40.
    Wilken N, Senécal J-L, Scheer U, Dabauvalle MC (1995) Localization of the Ran-GTP binding protein RanBP2 at the cytoplasmic side of the nuclear pore complex. Eur J Cell Biol 68:211–219PubMedGoogle Scholar
  41. 41.
    Kraemer D, Wozniak RW, Blobel G, Radu A (1994) The human CAN protein, a putative oncogene product associated with myeloid leukemogenesis, is a nuclear pore complex protein that faces the cytoplasm. Proc Natl Acad Sci USA 91:1519–1523PubMedGoogle Scholar
  42. 42.
    Bastos R, Ribas dP, Enarson M, Bodoor K, Burke B (1997) Nup84, a novel nucleoporin that is associated with CAN/Nup214 on the cytoplasmic face of the nuclear pore complex. J Cell Biol 137:989–1000CrossRefPubMedGoogle Scholar
  43. 43.
    Cronshaw JM, Matunis MJ (2003) The nuclear pore complex protein ALADIN is mislocalized in triple A syndrome. Proc Natl Acad Sci USA 100:5823–5827CrossRefPubMedGoogle Scholar
  44. 44.
    Walther TC, Pickersgill HS, Cordes VC, Goldberg MW, Allen TD, Mattaj IW, Fornerod M (2002) The cytoplasmic filaments of the nuclear pore complex are dispensable for selective nuclear protein import. J Cell Biol 158:63–77CrossRefPubMedGoogle Scholar
  45. 45.
    Bodoor K, Shaikh S, Enarson P, Chowdhury S, Salina D, Raharjo WH, Burke B (1999) Function and assembly of nuclear pore complex proteins. Biochem Cell Biol 77:321–329CrossRefPubMedGoogle Scholar
  46. 46.
    Soderqvist H, Hallberg E (1994) The large C-terminal region of the integral pore membrane protein, POM121, is facing the nuclear pore complex. Eur J Cell Biol 64:186–191PubMedGoogle Scholar
  47. 47.
    Greber UF, Senior A, Gerace L (1990) A major glycoprotein of the nuclear pore complex is a membrane-spanning polypeptide with a large lumenal domain and a small cytoplasmic tail. EMBO J 9:1495–1502PubMedGoogle Scholar
  48. 48.
    Grote M, Kubitscheck U, Reichelt R, Peters R (1995) Mapping of nucleoporins to the center of the nuclear pore complex by post-embedding immunogold electron microscopy. J Cell Sci 108:2963–2972PubMedGoogle Scholar
  49. 49.
    Pante N, Bastos R, McMorrow I, Burke B, Aebi U (1994) Interactions and three-dimensional localization of a group of nuclear pore complex proteins. J Cell Biol 126:603–617PubMedGoogle Scholar
  50. 50.
    Vasu S, Shah S, Orjalo A, Park M, Fischer WH, Forbes DJ (2001) Novel vertebrate nucleoporins Nup133 and Nup160 play a role in mRNA export. J Cell Biol 155:339–353CrossRefPubMedGoogle Scholar
  51. 51.
    Harel A, Orjalo AV, Vincent T, Lachish-Zalait A, Vasu S, Shah S, Zimmerman E, Elbaum M, Forbes DJ (2003) Removal of a single pore subcomplex results in vertebrate nuclei devoid of nuclear pores. Mol Cell 11:853–864CrossRefPubMedGoogle Scholar
  52. 52.
    Fontoura BM, Blobel G, Matunis MJ (1999) A conserved biogenesis pathway for nucleoporins: proteolytic processing of a 186-kilodalton precursor generates Nup98 and the novel nucleoporin, Nup96. J Cell Biol 144:1097–1112PubMedGoogle Scholar
  53. 53.
    Grandi P, Dang T, Pane N, Shevchenko A, Mann M, Forbes D, Hurt E (1997) Nup93, a vertebrate homologue of yeast Nic96p, forms a complex with a novel 205-kDa protein and is required for correct nuclear pore assembly. Mol Biol Cell 8:2017–2038PubMedGoogle Scholar
  54. 54.
    Miller BR, Powers M, Park M, Fischer W, Forbes DJ (2000) Identification of a new vertebrate nucleoporin, Nup188, with the use of a novel organelle trap assay. Mol Biol Cell 11:3381–3396PubMedGoogle Scholar
  55. 55.
    Cordes VC, Reidenbach S, Rackwitz HR, Franke WW (1997) Identification of protein p270/Tpr as a constitutive component of the nuclear pore complex-attached intranuclear filaments. J Cell Biol 136:515–529PubMedGoogle Scholar
  56. 56.
    Frosst P, Guan T, Subauste C, Hahn K, Gerace L (2002) Tpr is localized within the nuclear basket of the pore complex and has a role in nuclear protein export. J Cell Biol 156:617–630PubMedGoogle Scholar
  57. 57.
    Hase ME, Cordes VC (2003) Direct interaction with nup153 mediates binding of tpr to the periphery of the nuclear pore complex. Mol Biol Cell 14:1923–1940CrossRefPubMedGoogle Scholar
  58. 58.
    Radu A, Moore MS, Blobel G (1995) The peptide repeat domain of nucleoporin Nup98 functions as a docking site in transport across the nuclear pore complex. Cell 81:215–222PubMedGoogle Scholar
  59. 59.
    Griffis ER, Xu S, Powers MA (2003) Nup98 localizes to both nuclear and cytoplasmic sides of the nuclear pore and binds to two distinct nucleoporin subcomplexes. Mol Biol Cell 14:600–610CrossRefPubMedGoogle Scholar
  60. 60.
    Griffis ER, Altan N, Lippincott-Schwartz J, Powers MA (2002) Nup98 is a mobile nucleoporin with transcription-dependent dynamics. Mol Biol Cell 13:1282–1297PubMedGoogle Scholar
  61. 61.
    Belgareh N, Rabut G, Bai SW, van Overbeek M, Beaudouin J, Daigle N, Zatsepina OV, Pasteau F, Labas V, Fromont-Racine M, Ellenberg J, Doye V (2001) An evolutionarily conserved NPC subcomplex, which redistributes in part to kinetochores in mammalian cells. J Cell Biol 154:1147–1160CrossRefPubMedGoogle Scholar
  62. 62.
    Enninga J, Levay A, Fontoura BM (2003) Sec13 shuttles between the nucleus and the cytoplasm and stably interacts with Nup96 at the nuclear pore complex. Mol Cell Biol 23:7271–7284CrossRefPubMedGoogle Scholar
  63. 63.
    Radu A, Blobel G, Wozniak RW (1993) Nup155 is a novel nuclear pore complex protein that contains neither repetitive sequence motifs nor reacts with WGA. J Cell Biol 121:1–9PubMedGoogle Scholar
  64. 64.
    Guan T, Kehlenbach RH, Schirmer EC, Kehlenbach A, Fan F, Clurman BE, Arnheim N, Gerace L (2000) Nup50, a nucleoplasmically oriented nucleoporin with a role in nuclear protein export. Mol Cell Biol 20:5619–5630CrossRefPubMedGoogle Scholar
  65. 65.
    Lindsay ME, Plafker K, Smith AE, Clurman BE, Macara IG (2002) Npap60/Nup50 is a tri-stable switch that stimulates importin-alpha:beta-mediated nuclear protein import. Cell 110:349–360CrossRefPubMedGoogle Scholar
  66. 66.
    Nozawa K, Fritzler MJ, Von Mühlen CA, Chan EKL (2004) Giantin is the major Golgi autoantigen in human anti-Golgi complex sera. Arthritis Res Ther 6:R95–R102CrossRefPubMedGoogle Scholar
  67. 67.
    Bodoor K, Shaikh S, Salina D, Raharjo WH, Bastos R, Lohka M, Burke B (1999) Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis. J Cell Sci 112:2253–2264PubMedGoogle Scholar
  68. 68.
    Stukenberg PT, Macara IG (2003) The kinetochore NUP tials. Nat Cell Biol 5:945–947CrossRefPubMedGoogle Scholar
  69. 69.
    Wang X, Babu JR, Harden JM, Jablonski SA, Gazi MH, Lingle WL, de Groen PC, Yen TJ, van Deursen JM (2001) The mitotic checkpoint protein hBUB3 and the mRNA export factor hRAE1 interact with GLE2p-binding sequence (GLEBS)-containing proteins. J Biol Chem 276:26559–26567CrossRefPubMedGoogle Scholar
  70. 70.
    Joseph J, Tan SH, Karpova TS, McNally JG, Dasso M (2002) SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles. J Cell Biol 156:595–602CrossRefPubMedGoogle Scholar
  71. 71.
    Salina D, Enarson P, Rattner JB, Burke B (2003) Nup358 integrates nuclear envelope breakdown with kinetochore assembly. J Cell Biol 162:991–1001CrossRefPubMedGoogle Scholar
  72. 72.
    McKeon FD, Tuffanelli DL, Fukuyama K, Kirschner MW (1983) Autoimmune response directed against conserved determinants of nuclear envelope proteins in a patient with linear scleroderma. Proc Natl Acad Sci USA 80:4374–4378PubMedGoogle Scholar
  73. 73.
    Guilly MN, Danon F, Brouet JC, Bornens M, Courvalin JC (1987) Autoantibodies to nuclear lamin B in a patient with thrombocytopenia. Eur J Cell Biol 43:266–272PubMedGoogle Scholar
  74. 74.
    Lassoued K, Guilly M-N, Danon F, Andre C, Dhumeaux D, Clauvel J-P, Brouet J-C, Seligmann M, Courvalin J-C (1988) Antinuclear autantibodies specific for lamins. Ann Intern Med 108:829–833PubMedGoogle Scholar
  75. 75.
    Reeves WH, Chaudhary N, Salerno A, Blobel G (1987) Lamin B autoantibodies in sera of certain patients with systemic lupus erythematosus. J Exp Med 165:750–762PubMedGoogle Scholar
  76. 76.
    Courvalin J-C, Lassoued K, Worman HJ, Blobel G (1990) Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J Exp Med 172:961–967PubMedGoogle Scholar
  77. 77.
    Dagenais A, Bibo-Hardy V, Senécal J-L (1988) A novel autoantibody causing a peripheral fluorescent antinuclear antibody pattern is specific for nuclear pore complexes. Arthritis Rheum 31:1322–1327Google Scholar
  78. 78.
    Ou Y, Enarson P, Rattner JB, Barr W, Fritzler MJ (2004) The nuclear pore complex protein Tpr is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence. Clin Exp Immunol 136:379–387CrossRefPubMedGoogle Scholar
  79. 79.
    Aaron LA, Buchwald D (2001) A review of the evidence for overlap among unexplained clinical conditions. Ann Intern Med 134:868–881PubMedGoogle Scholar
  80. 80.
    Tan EM, Feltkamp TEW, Smolen JS, Butcher B, Dawkins R, Fritzler MJ, Gordon T, Hardin JA, Kalden JR, Lahita RG, Maini RN, McDougal JS, Rothfield NF, Smeenk RJ, Takasaki Y, Wiik A, Koziol JA (1997) Range of antinuclear antibodies in “healthy” individuals. Arthritis Rheum 40:1601–1611PubMedGoogle Scholar
  81. 81.
    Lozano F, Pares A, Borche L, Plana M, Gallart T, Rodes J, Vives J (1988) Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis. Hepatology 8:930–938PubMedGoogle Scholar
  82. 82.
    Courvalin J-C, Lassoued K, Bartnik E, Blobel G, Wozniak RW (1990) The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. J Clin Invest 86:279–285PubMedGoogle Scholar
  83. 83.
    Miyachi K, Shibata M, Onozuka Y, Kikuchi F, Imai N, Horigome T (1996) Primary biliary cirrhosis sera recognize not only gp210 but also proteins of the p62 complex bearing N-acetyl glucosamine residues from rat liver nuclear envelope. Anti-p62 complex antibody in PBC. Mol Biol Rep 23:227–234PubMedGoogle Scholar
  84. 84.
    Bandin O, Courvalin J-C, Poupon R, Dubel J, Homberg JC, Johanet C (1996) Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis. Hepatology 23:1020–1024PubMedGoogle Scholar
  85. 85.
    Itoh S, Ichida T, Yoshida T, Hayakawa A, Uchida M, Tashiro-Itoh T, Matsuda Y, Ishihara K, Asakura H (1998) Autoantibodies against a 210 kDa glycoprotein of the nuclear pore complex as a prognostic marker in patients with primary biliary cirrhosis. J Gastroenterol Hepatol 13:257–265PubMedGoogle Scholar
  86. 86.
    Nickowitz RE, Wozniak RW, Schaffner F, Worman HJ (1994) Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis. Gastroenterology 106:193–199PubMedGoogle Scholar
  87. 87.
    Lassoued K, Brenard R, Degos F, Courvalin J-C, Andre C, Danon F, Brouet J-C, Zine-el-Abidine Y, Zafrani S, et al (1990) Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis. Gastroenterology 99:181–186PubMedGoogle Scholar
  88. 88.
    Nickowitz RE, Worman HJ (1993) Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein gp210. J Exp Med 178:2237–2242PubMedGoogle Scholar
  89. 89.
    Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E (1995) Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210. J Exp Med 182:1159–1162PubMedGoogle Scholar
  90. 90.
    Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E (1996) Anti-gp210 antibodies in sera of patients with primary biliary cirrhosis. Identification of a 64 kD fragment of gp210 as a major epitope. Hum Antibodies Hybridomas 7:167–174PubMedGoogle Scholar
  91. 91.
    Invernizzi P, Podda M, Battezzati PM, Crosignani A, Zuin M, Hitchman E, Maggioni M, Meroni PL, Penner E, Wesierska-Gadek J (2001) Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J Hepatol 34:366–372CrossRefPubMedGoogle Scholar
  92. 92.
    Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E (1996) Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis. Gastroenterology 110:840–847PubMedGoogle Scholar
  93. 93.
    Kraemer DM, Kraus MR, Kneitz C, Tony HP (2003) Nucleoporin p62 antibodies in a case of mixed connective tissue disease. Clin Diagn Lab Immunol 10:329–331CrossRefPubMedGoogle Scholar
  94. 94.
    Senécal J-L, Rauch J, Grodzicky T, Raynauld J-P, Uthman I, Nava A, Guimond M, Raymond Y (1999) Strong association of autoantibodies to human nuclear lamin B1 with lupus anticoagulant antibodies in systemic lupus erythematosus. Arthritis Rheum 42:1347–1353Google Scholar
  95. 95.
    Wilken N, Kossner U, Senécal J-L, Scheer U, Dabauvalle MC (1993) Nup180, a novel nuclear pore complex protein localizing to the cytoplasmic ring and associated fibrils. J Cell Biol 123:1345–1354PubMedGoogle Scholar
  96. 96.
    Gregorio GV, Choudhuri K, Ma Y, Vegnente A, Mieli-Vergani G, Vergani D (1999) Mimicry between the hepatitis B virus DNA polymerase and the antigenic targets of nuclear and smooth muscle antibodies in chronic hepatitis B virus infection. J Immunol 162:1802–1810PubMedGoogle Scholar
  97. 97.
    Kunkel HG, Holman HR, Deicher HRG (1960) Multiple “autoantibodies” to cell constituents in systemic lupus erythematosus. Ciba Found Symp 1:429–437Google Scholar
  98. 98.
    Senécal JL, Raymond Y (1991) Autoantibodies to DNA, lamins, and pore complex proteins produce distinct peripheral fluorescent antinuclear antibody patterns on the HEp-2 substrate. Arthritis Rheum 34:249–251Google Scholar
  99. 99.
    Daigle N, Beaudouin J, Hartnell L, Imreh G, Hallberg E, Lippincott-Schwartz J, Ellenberg J (2001) Nuclear pore complexes form immobile networks and have a very low turnover in live mammalian cells. J Cell Biol 154:71–84PubMedGoogle Scholar
  100. 100.
    Miller BR, Forbes DJ (2000) Purification of the vertebrate nuclear pore complex by biochemical criteria. Traffic 1:941–951CrossRefPubMedGoogle Scholar
  101. 101.
    Kita K, Omata S, Horigome T (1993) Purification and characterization of a nuclear pore glycoprotein complex containing p62. J Biochem (Tokyo) 113:377–382Google Scholar
  102. 102.
    Tartakovsky F, Worman HJ (1995) Detection of Gp210 autoantibodies in primary biliary cirrhosis using a recombinant protein containing the predominant autoepitope. Hepatology 21:495–500PubMedGoogle Scholar
  103. 103.
    Dreger M, Bengtsson L, Schoneberg T, Otto H, Hucho F (2001) Nuclear envelope proteomics: novel integral membrane proteins of the inner nuclear membrane. Proc Natl Acad Sci USA 98:11943–11948PubMedGoogle Scholar
  104. 104.
    Schirmer EC, Florens L, Guan T, Yates JR, III, Gerace L (2003) Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 301:1380–1382CrossRefPubMedGoogle Scholar
  105. 105.
    Worman HJ, Feng L, Mamiya N (1998) Molecular biology and the diagnosis and treatment of liver diseases. World J Gastroenterol 4:185–191PubMedGoogle Scholar
  106. 106.
    Ostlund C, Worman HJ (2003) Nuclear envelope proteins and neuromuscular diseases. Muscle Nerve 27:393–406CrossRefPubMedGoogle Scholar
  107. 107.
    Vignali DA (2000) Multiplexed particle-based flow cytometric assays. J Immunol Methods 21:243–255CrossRefGoogle Scholar
  108. 108.
    Willman JH, Hill HR, Martins TB, Jankowski TD, Ashwood ER, Litwin CM (2001) Multiplex analysis of heterophil antibodies in patients with intermediate HIV immunoassay results. Am J Clin Pathol 115:764–769CrossRefPubMedGoogle Scholar
  109. 109.
    Robinson WH, Steinman L, Utz PJ (2002) Proteomics technologies for the study of autoimmune disease. Arthritis Rheum 46:885–893Google Scholar
  110. 110.
    Robinson WH, DiGennaro C, Hueber W, Haab BB, Kamachi M, Dean EJ, Fournel S, Fong D, Genovese MC, De Vegvar HEN, Skriner K, Hirschberg DL, Morris RI, Muller S, Pruijn GJ, Van Venrooij WJ, Smolen JS, Brown PO, Steinman L, Utz PJ (2002) Autoantigen microarrays for multiplex characterization of autoantibody responses. Nat Med 8:295–301CrossRefPubMedGoogle Scholar
  111. 111.
    Fritzler MJ (2002) New technologies in the detection of autoantibodies. In: Conrad K, Fritzler MJ, Meurer M, Sack U, Shoenfeld Y (eds) Autoantigens, autoantibodies, autoimmunity. Pabst, Lengerich, pp 50–63Google Scholar
  112. 112.
    Sukegawa J, Blobel G (1993) A nuclear pore complex protein that contains zinc finger motifs, binds DNA, and faces the nucleoplasm. Cell 72:29–38CrossRefPubMedGoogle Scholar
  113. 113.
    Radu A, Blobel G, Wozniak RW (1994) Nup107 is a novel nuclear pore complex protein that contains a leucine zipper. J Biol Chem 269:17600–17605PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • P. Enarson
    • 1
  • J. B. Rattner
    • 1
  • Y. Ou
    • 1
  • K. Miyachi
    • 2
  • T. Horigome
    • 3
  • M. J. Fritzler
    • 4
    Email author
  1. 1.Department of Anatomy and Cell Biology, Faculty of MedicineUniversity of CalgaryCalgaryCanada
  2. 2.Health Sciences Research InstituteKanagawaJapan
  3. 3.Department of Chemistry, Faculty of SciencesNiigata UniversityNiigataJapan
  4. 4.Department of Medicine, Faculty of MedicineUniversity of CalgaryCalgaryCanada

Personalised recommendations