Antinuclear antibodies as ancillary markers in primary biliary cirrhosis

Expert Review of Molecular Diagnostics

Volumn 12, Issue 1, 2012, Pages 65-74

  Granito, Alessandro ^a   Muratori, Paolo ^a   Quarneti, Chiara ^a   Pappas, Georgios ^a   Cicola, Ronny ^a   Muratori, Luigi ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

Author keywords

antinuclear antibodies; gp210; multiple nuclear dots; nuclear pore complex; prognosis; rim like membranous; sp100; surrogate markers

Indexed keywords

ANTINUCLEAR ANTIBODY; AUTOANTIGEN; BIOLOGICAL MARKER; GLYCOPROTEIN; GLYCOPROTEIN GP 210; LAMIN B; LAMIN B RECEPTOR; PROMYELOCYTIC LEUKEMIA PROTEIN; PROTEIN P62; RECEPTOR; SP100 PROTEIN; SP140 PROTEIN; SUMO PROTEIN; UNCLASSIFIED DRUG;

ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; IMMUNOBLOTTING; IMMUNOFLUORESCENCE; PRIMARY BILIARY CIRRHOSIS; PROGNOSIS; PROTEIN EXPRESSION; REVIEW; WESTERN BLOTTING;

ANTIBODIES, ANTINUCLEAR; ANTIGENS, NUCLEAR; AUTOANTIGENS; BIOLOGICAL MARKERS; BLOTTING, WESTERN; ENZYME-LINKED IMMUNOSORBENT ASSAY; EPITOPE MAPPING; FLUORESCENT ANTIBODY TECHNIQUE, INDIRECT; HUMANS; LIVER CIRRHOSIS, BILIARY; MEMBRANE GLYCOPROTEINS; NUCLEAR PORE COMPLEX PROTEINS; NUCLEAR PROTEINS; PROGNOSIS; RECEPTORS, CYTOPLASMIC AND NUCLEAR; TRANSCRIPTION FACTORS; TUMOR SUPPRESSOR PROTEINS;

EID: 82955247118     PISSN: 14737159     EISSN: 17448352     Source Type: Journal    
DOI: 10.1586/erm.11.82     Document Type: Review

References (80)

1. Kaplan MM, Gershwin ME. Primary biliary cirrhosis. N. Engl. J. Med. 353(12), 1261-1273 (2005). (Pubitemid 41345948)
2. Muratori L, Granito A, Muratori P, Pappas G, Bianchi FB. Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: Diagnostic and prognostic value. Clin. Liver Dis. 12(2), 261-276 vii (2008). A comprehensive review dealing with diagnostic and prognostic value of antimitochondrial antibodies and antinuclear antibodies (ANA). (Pubitemid 351635893)
3. Bogdanos DP, Komorowski L. Disease-specific autoantibodies in primary biliary cirrhosis. Clin. Chim. Acta 412(7-8), 502-512 (2011). An overview of the diagnostic significance of autoantibodies in primary biliary cirrhosis (PBC) and techniques used for their determination.
4. Remmel T, Piirsoo A, Koiveer A, Remmel H, Uibo R, Salupere V. Clinical significance of different antinuclear antibodies patterns in the course of primary biliary cirrhosis. Hepatogastroenterology 43(11), 1135-1140 (1996). (Pubitemid 26358504)
5. Marasini B, Gagetta M, Rossi V, Ferrari P. Rheumatic disorders and primary biliary cirrhosis: An appraisal of 170 Italian patients. Ann. Rheum. Dis. 60(11), 1046-1049 (2001). (Pubitemid 32989177)
6. Muratori P, Muratori L, Ferrari R et al. Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am. J. Gastroenterol. 98(2), 431-437 (2003). A study that analyzed antinuclear reactivities of PBC patients in detail and correlated the fine specificities observed with clinical, biochemical and immunologic parameters. (Pubitemid 36232395)
7. Yang WH, Yu JH, Nakajima A, Neuberg D, Lindor K, Bloch DB. Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure? Clin. Gastroenterol. Hepatol. 2(12), 1116-1122 (2004). (Pubitemid 40037643)
8. Rigopoulou EI, Davies ET, Pares A et al. Prevalence and clinical significance of isotype specific antinuclear antibodies in primary biliary cirrhosis. Gut 54(4), 528-532 (2005). Very interesting study showing a high prevalence of PBC-specific ANA when investigated at the level of IgG isotype, and demonstrating that PBC-specific ANA of IgG3 isotype are associated with more severe disease. (Pubitemid 40395506)
9. Walker JG, Doniach D, Roitt IM, Sherlock S. Serological tests in diagnosis of primary biliary cirrhosis. Lancet 1(7390), 827-831 (1965).
10. Doniach D, Roitt IM, Walker JG, Sherlock S. Tissue antibodies in primary biliary cirrhosis, active chronic (lupoid) hepatitis, cryptogenic cirrhosis and other liver diseases and their clinical implications. Clin. Exp. Immunol. 1(3), 237-262 (1966).
11. 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. 10(4), 438-445 (1995).
12. Rigamonti C, Shand LM, Feudjo M et al. Clinical features and prognosis of primary biliary cirrhosis associated with systemic sclerosis. Gut 55(3), 388-394 (2006). (Pubitemid 43268280)
13. Granito A, Muratori P, Muratori L et al. Antibodies to SS-A/Ro-52kD and centromere in autoimmune liver disease: A clue to diagnosis and prognosis of primary biliary cirrhosis. Aliment Pharmacol. Ther. 26(6), 831-838 (2007). Detailed analysis of antinuclear reactivities classically detected in rheumatological patients, in autoimmune liver diseases. (Pubitemid 47346710)
14. Chou MJ, Lee SL, Chen TY, Tsay GJ. Specificity of antinuclear antibodies in primary biliary cirrhosis. Ann. Rheum. Dis. 54(2), 148-151 (1995).
15. Agmon-Levin N, Shapira Y, Selmi C et al. A comprehensive evaluation of serum autoantibodies in primary biliary cirrhosis. J. Autoimmun. 34(1), 55-58 (2010).
16. Invernizzi P, Selmi C, Ranftler C, Podda M, Wesierska-Gadek J. Antinuclear antibodies in primary biliary cirrhosis. Semin. Liver Dis. 25(3), 298-310 (2005). An exhaustive review of ANA in PBC. (Pubitemid 41254577)
17. Invernizzi P, Podda M, Battezzati PM et al. Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J. Hepatol. 34(3), 366-372 (2001). Demonstrates the prognostic significance of ANA directed against nuclear pore complex components. (Pubitemid 32240814)
18. Szostecki C, Guldner HH, Will H. Autoantibodies against 'nuclear dots' in primary biliary cirrhosis. Semin. Liver Dis. 17(1), 71-78 (1997). (Pubitemid 27157373)
19. Borden KL. Pondering the promyelocytic leukemia protein (PML) puzzle: Possible functions for PML nuclear bodies. Mol. Cell Biol. 22(15), 5259-5269 (2002). (Pubitemid 34755740)
20. Worman HJ, Courvalin JC. Antinuclear antibodies specific for primary biliary cirrhosis. Autoimmun. Rev. 2(4), 211-217 (2003). (Pubitemid 36793945)
21. Janka C, Selmi C, Gershwin ME, Will H, Sternsdorf T. Small ubiquitin-related modifiers: A novel and independent class of autoantigens in primary biliary cirrhosis. Hepatology 41(3), 609-616 (2005). (Pubitemid 40289510)
22. Granito A, Yang WH, Muratori L et al. PML nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis. Am. J. Gastroenterol. 105(1), 125-131 (2010).
23. Szostecki C, Krippner H, Penner E, Bautz FA. Autoimmune sera recognize a 100 kD nuclear protein antigen (sp-100). Clin. Exp. Immunol. 68(1), 108-116 (1987). (Pubitemid 17044783)
24. Szostecki C, Guldner HH, Netter HJ, Will H. Isolation and characterization of cDNA encoding a human nuclear antigen predominantly recognized by autoantibodies from patients with primary biliary cirrhosis. J. Immunol. 145(12), 4338-4347 (1990).
25. Bluthner M, Schafer C, Schneider C, Bautz FA. Identification of major linear epitopes on the sp100 nuclear PBC autoantigen by the gene-fragment phage-display technology. Autoimmunity 29(1), 33-42 (1999). (Pubitemid 29097570)
26. Powell F, Schroeter AL, Dickson ER. Antinuclear antibodies in primary biliary cirrhosis. Lancet 1(8371), 288-289 (1984). (Pubitemid 14178545)
27. Zuchner D, Sternsdorf T, Szostecki C, Heathcote EJ, Cauch-Dudek K, Will H. Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatology 26(5), 1123-1130 (1997). (Pubitemid 27509292)
28. Muratori P, Muratori L, Cassani F et al. Anti-multiple nuclear dots (anti-MND) and anti-SP100 antibodies in hepatic and rheumatological disorders. Clin. Exp. Immunol. 127(1), 172-175 (2002). (Pubitemid 34155473)
29. Dubel L, Farges O, Courvalin JC, Sebagh M, Johanet C. Persistence of gp210 and multiple nuclear dots antibodies does not correlate with recurrence of primary biliary cirrhosis 6 years after liver transplantation. J. Hepatol. 28(1), 169-170 (1998). (Pubitemid 28122518)
30. Luettig B, Boeker KH, Schoessler W et al. The antinuclear autoantibodies Sp100 and gp210 persist after orthotopic liver transplantation in patients with primary biliary cirrhosis. J. Hepatol. 28(5), 824-828 (1998). (Pubitemid 28223487)
31. Vergani D, Bogdanos DP. Positive markers in AMA-negative PBC. Am. J. Gastroenterol. 98(2), 241-243 (2003). (Pubitemid 36232366)
32. Pawlotsky JM, Andre C, Metreau JM, Beaugrand M, Zafrani ES, Dhumeaux D. Multiple nuclear dots antinuclear antibodies are not specific for primary biliary cirrhosis. Hepatology 16(1), 127-131 (1992).
33. Wichmann I, Montes-Cano MA, Respaldiza N et al. Clinical significance of anti-multiple nuclear dots/Sp100 autoantibodies. Scand. J. Gastroenterol. 38(9), 996-999 (2003). (Pubitemid 37153630)
34. Bogdanos DP, Vergani D, Muratori P, Muratori L, Bianchi FB. Specificity of anti-sp100 antibody for primary biliary cirrhosis. Scand. J. Gastroenterol. 39(4), 405-406 author reply 407 (2004). (Pubitemid 38526735)
35. Rigopoulou EI, Dalekos GN. Anti-sp100 antibodies in primary biliary cirrhosis. Scand. J. Gastroenterol. 39(4), 406-407; author reply 407 (2004). (Pubitemid 38526736)
36. Granito A, Muratori P, Muratori L et al. Antinuclear antibodies giving the 'multiple nuclear dots' or the 'rim-like/membranous' patterns: Diagnostic accuracy for primary biliary cirrhosis. Aliment Pharmacol. Ther. 24(11-12), 1575-1583 (2006). (Pubitemid 44915205)
37. De Thé H, Chomienne C, Lanotte M, Degos L, Dejean A. The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor a gene to a novel transcribed locus. Nature 347(6293), 558-561 (1990).
38. Sternsdorf T, Grotzinger T, Jensen K, Will H. Nuclear dots: Actors on many stages. Immunobiology 198(1-3), 307-331 (1997). (Pubitemid 28021406)
39. Sternsdorf T, Guldner HH, Szostecki C, Grotzinger T, Will H. Two nuclear dot-Associated proteins, PML and Sp100, are often co-Autoimmunogenic in patients with primary biliary cirrhosis. Scand. J. Immunol. 42(2), 257-268 (1995).
40. Ruffatti A, Arslan P, Floreani A et al. Nuclear membrane-staining antinuclear antibody in patients with primary biliary cirrhosis. J. Clin. Immunol. 5(5), 357-361 (1985). (Pubitemid 16257940)
41. Ye Q, Worman HJ. Primary structure analysis and lamin B and DNA binding of human LBR, an integral protein of the nuclear envelope inner membrane. J. Biol. Chem. 269(15), 11306-11311 (1994). (Pubitemid 24200343)
42. Worman HJ, Lazaridis I, Georgatos SD. Nuclear lamina heterogeneity in mammalian cells. Differential expression of the major lamins and variations in lamin B phosphorylation. J. Biol. Chem. 263(24), 12135-12141 (1988).
43. Wesierska-Gadek J, Hohenuer H, Hitchman E, Penner E. Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis. Gastroenterology 110(3), 840-847 (1996). (Pubitemid 26071851)
44. Reeves WH, Chaudhary N, Salerno A, Blobel G. Lamin B autoantibodies in sera of certain patients with systemic lupus erythematosus. J. Exp. Med. 165(3), 750-762 (1987). (Pubitemid 17059451)
45. Lassoued K, Brenard R, Degos F et al. 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(1), 181-186 (1990). (Pubitemid 20202507)
46. Senecal JL, Ichiki S, Girard D, Raymond Y. Autoantibodies to nuclear lamins and to intermediate filament proteins: Natural, pathologic or pathogenic? J. Rheumatol. 20(2), 211-219 (1993). (Pubitemid 23066026)
47. Konstantinov K, Foisner R, Byrd D et al. Integral membrane proteins associated with the nuclear lamina are novel autoimmune antigens of the nuclear envelope. Clin. Immunol. Immunopathol. 74(1), 89-99 (1995).
48. Bandin O, Courvalin JC, Poupon R, Dubel L, Homberg JC, Johanet C. 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(5), 1020-1024 (1996). (Pubitemid 26137040)
49. Miyachi K, Shibata M, Onozuka Y, Kikuchi F, Imai N, Horigome T. Primary biliary cirrhosis sera recognize not only gp210 but also proteins of the p62 complex bearing N-Acetylglucosamine residues from rat liver nuclear envelope. Anti-p62 complex antibody in PBC. Mol. Biol. Rep. 23(3-4), 227-234 (1996). (Pubitemid 27153045)
50. Lozano F, Pares A, Borche L et al. Autoantibodies against nuclear envelope-Associated proteins in primary biliary cirrhosis. Hepatology 8(4), 930-938 (1988).
51. Lassoued K, Guilly MN, Andre C et al. Autoantibodies to 200 kD polypeptide(s) of the nuclear envelope: A new serologic marker of primary biliary cirrhosis. Clin. Exp. Immunol. 74(2), 283-288 (1988).
52. Courvalin JC, Lassoued K, Bartnik E, Blobel G, Wozniak RW. 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(1), 279-285 (1990). (Pubitemid 20227003)
53. Nickowitz RE, Worman HJ. 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(6), 2237-2242 (1993). (Pubitemid 23344884)
54. Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E. Autoantibodies from patients with primary biliary cirrhosis preferentially react with the amino-terminal domain of nuclear pore complex glycoprotein gp210. J. Exp. Med. 182(4), 1159-1162 (1995).
55. Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E. Autoantibodies against constituents of nuclear pore complexes in patients with primary biliary cirrhosis and autoimmune hepatitis. Acta Biochim. Pol. 42(2), 197-200 (1995).
56. Wesierska-Gadek J, Hohenauer H, Hitchman E, Penner E. 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(4), 167-174 (1996). (Pubitemid 27207867)
57. Nickowitz RE, Wozniak RW, Schaffner F, Worman HJ. Autoantibodies against integral membrane proteins of the nuclear envelope in patients with primary biliary cirrhosis. Gastroenterology 106(1), 193-199 (1994). (Pubitemid 24011881)
58. Itoh S, Ichida T, Yoshida T et al. 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(3), 257-265 (1998). (Pubitemid 28183956)
59. Miyachi K, Hankins RW, Matsushima H et al. Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: A multicenter study. J. Autoimmun. 20(3), 247-254 (2003). (Pubitemid 36561490)
60. Wesierska-Gadek J, Penner E, Battezzati PM et al. Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology 43(5), 1135-1144 (2006). (Pubitemid 43724638)
61. Courvalin JC, Lassoued K, Worman HJ, Blobel G. Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J. Exp. Med. 172(3), 961-967 (1990). (Pubitemid 20301243)
62. Worman HJ, Yuan J, Blobel G, Georgatos SD. A lamin B receptor in the nuclear envelope. Proc. Natl Acad. Sci. USA 85(22), 8531-8534 (1988). (Pubitemid 19024995)
63. Lin F, Noyer CM, Ye Q, Courvalin JC, Worman HJ. Autoantibodies from patients with primary biliary cirrhosis recognize a region within the nucleoplasmic domain of inner nuclear membrane protein LBR. Hepatology 23(1), 57-61 (1996). (Pubitemid 26012092)
64. Orton SM, Peace-Brewer A, Schmitz JL, Freeman K, Miller WC, Folds JD. Practical evaluation of methods for detection and specificity of autoantibodies to extractable nuclear antigens. Clin. Diagn. Lab Immunol. 11(2), 297-301 (2004). (Pubitemid 38380809)
65. Briolay J, Gioud M, Monier JC et al. Antinuclear antibodies detected by indirect immunofluorescence on HEp2 cells and by immunoblotting in patients with systemic sclerosis. Autoimmunity 2(2), 165-176 (1989). (Pubitemid 19058077)
66. Eissfeller P, Sticherling M, Scholz D et al. Comparison of different test systems for simultaneous autoantibody detection in connective tissue diseases. Ann. NY Acad. Sci. 1050, 327-339 (2005). (Pubitemid 41129451)
67. Muratori P, Granito A, Pappas G et al. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am. J. Gastroenterol. 104(6), 1420-1425 (2009).
68. Efe C, Purnak T, Ozaslan E, Wahlin S. The serological profile of the autoimmune hepatitis/primary biliary cirrhosis overlap syndrome. Am. J. Gastroenterol. 105(1), 226, author reply 226-227 (2010).
69. Prince M, Chetwynd A, Newman W, Metcalf JV, James OF. Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: Follow-up for up to 28 years. Gastroenterology 123(4), 1044-1051 (2002).
70. Springer J, Cauch-Dudek K, O'Rourke K, Wanless IR, Heathcote EJ. Asymptomatic primary biliary cirrhosis: A study of its natural history and prognosis. Am. J. Gastroenterol. 94(1), 47-53 (1999). (Pubitemid 29063443)
71. Nakamura M, Shimizu-Yoshida Y, Takii Y et al. Antibody titer to gp210-C terminal peptide as a clinical parameter for monitoring primary biliary cirrhosis. J. Hepatol. 42(3), 386-392 (2005). (Pubitemid 40254254)
72. Nakamura M, Kondo H, Mori T et al. Anti-gp210 and anti-centromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology 45(1), 118-127 (2007). The authors suggest two different patterns of disease progression in PBC: A 'hepatic failure type', related to the presence of anti-gp210 antibodies and a 'portal hypertension type' related to the presence of anticentromere antibodies. (Pubitemid 46144371)
73. Bogdanos DP, Liaskos C, Pares A et al. Anti-gp210 antibody mirrors disease severity in primary biliary cirrhosis. Hepatology 45(6), 1583; author reply 1583-1584 (2007).
74. Sfakianaki O, Koulentaki M, Tzardi M et al. Peri-nuclear antibodies correlate with survival in Greek primary biliary cirrhosis patients. World J. Gastroenterol. 16(39), 4938-4943 (2010).
75. Vergani D, Alvarez F, Bianchi FB et al. Liver autoimmune serology: A consensus statement from the committee for autoimmune serology of the International autoimmune hepatitis group. J. Hepatol. 41(4), 677-683 (2004). An internationally representative committee defines guidelines for more reliable testing. (Pubitemid 39297806)
76. Rigopoulou EI, Dalekos GN. Molecular diagnostics of primary biliary cirrhosis. Expert Opin. Med. Diagn. 2(6), 621-634 (2008). (Pubitemid 351997852)
77. Liu H, Norman GL, Shums Z et al. PBC screen: An IgG/IgA dual isotype ELISA detecting multiple mitochondrial and nuclear autoantibodies specific for primary biliary cirrhosis. J. Autoimmun. 35(4), 436-442 (2010).
78. Oertelt S, Rieger R, Selmi C et al. A sensitive bead assay for antimitochondrial antibodies: Chipping away at AMA-negative primary biliary cirrhosis. Hepatology 45(3), 659-665 (2007). (Pubitemid 46450617)
79. Nakamura M, Yasunami M, Kondo H et al. Analysis of HLA-DRB1 polymorphisms in Japanese patients with primary biliary cirrhosis (PBC): The HLA-DRB1polymorphism determines the relative risk of antinuclear antibodies for disease progression in PBC. Hepatol. Res. 40(5), 494-504 (2010).
80. Wiik AS, Hoier-Madsen M, Forslid J, Charles P, Meyrowitsch J. Antinuclear antibodies: A contemporary nomenclature using HEp-2 cells. J. Autoimmun. 35(3), 276-290 (2010).