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© Borgis - Postępy Nauk Medycznych 11/2011, s. 963-968
*Alicja Bauer
Antimitochondrial and antinuclear antibodies in primary biliary cirrhosis**
Przeciwciała antymitochondrialne i antyjądrowe w pierwotnej żółciowej marskości wątroby
Department of Biochemistry and Molecular Biology, Medical Center of Postgraduate Education, Warsaw
Head of Department: prof dr hab. Barbara Czarnocka
Pierwotna żółciowa marskość (PBC) jest przewlekłą chorobą wątroby o nieznanej etiologii. Rozpoczyna sie od zmian zapalnych w małych kanalikach żółciowych, powoli doprowadzając do patologicznych zmian w tkance wątrobowej i całkowitej marskości wątroby. Przeciwciała występujące w surowicach pacjentów są przydatnym narzędziem uzupełniającym diagnozę choroby. Najbardziej czułym i swoistym markerem immunologicznym PBC są przeciwciała antimitochondrialne (AMA), skierowane przeciwko kompleksowi dehydrogenazy pirogronianowej, zlokalizowanemu w wewnętrznej błonie mitochondrialnej. Ponadto dla ok. 50% pacjentów z PBC charakterystyczne są przeciwciała przeciwjądrowe (ANA), gdzie głównymi autoantygenami są białka otoczki jądrowej: glikoproteina gp210, nukleoporyna p62 i receptor laminy B (LBR). Zwłaszcza przeciwciała skierowane przeciwko antygenom gp210 i p62 są bardzo specyficzne dla PBC i wykrywanie ich może być pomocne w diagnostyce serologicznej, zwłaszcza w przypadkach, w których nie wykryto przeciwciał przeciwmitochondrialnych. Istnieją doniesienia wskazujące na związek obecności przeciwciał skierowanych przeciwko białkom kompleksu porowego i gorszym rokowaniem w przebiegu PBC. Badania przeprowadzone w różnych regionach świata, wykazały też znaczne różnice w częstości występowania (9-45%) przeciwciał przeciwko białku gp210 w PBC. W ciągu ostatnich lat kolejne struktury jądrowe zostały zidentyfikowane jako istotne dla przeciwciał ANA w PBC. Należą do nich między innymi białko Sp100 i białka białaczki promielocytowej. Specyficzne przeciwciała przeciwjądrowe mogą stanowić nowe ważne, narzędzie w procesie diagnostycznym pacjentów z PBC.
Primary biliary cirrhosis (PBC) is a chronic liver disease of unknown etiology. It starts with inflammatory changes in the small biliary ducts and slowly develops pathological changes in the tissue, leading to complete liver cirrhosis. Serum autoantibodies are crucial tools for diagnosis of PBC. Antimitochondrial autoantibodies (AMA), directed against the 2-oxoacid-dehydrogenase complex of the inner mitochondrial membrane, are the most sensitive and specific immunologic markers of PBC. Additionally 50% of PBC patients have antinuclear antibodies (ANA). The nuclear envelope proteins have been identified as target of ANA reactivity. A part of PBC patients develops antibodies against constituents of the nuclear pore complex – gp210 protein, p62 nucleoporin and lamin B receptor (LBR). Antibodies to these antigens such as gp210 protein and p62 nucleoporin are highly specific for PBC and can aid in the serologic diagnosis, especially in cases in which antimitochondrial antibodies are not detectable. A review of several studies performed in various regions of the world showed wide differences in prevalence (9-45%) of antibodies against gp210 protein in PBC. There are reports indicating an association of positivity for antibodies against the nuclear pore complex with poor outcome of PBC. During the last years a number of another nuclear structures have been recognized as a specific targets of ANAs in PBC. These include Sp100 and promyelocytic leukemia proteins. Specific antinuclear antibodies will provide an important, novel clinical tool in diagnostic process of patients with PBC.
Primary biliary cirrhosis is a chronic, slowly progressive cholestatic liver disease with features of an autoimmune disorder, with unknown etiology. It starts with inflammatory changes in the small biliary ducts and after developing pathological changes in the tissue, leading to complete liver cirrhosis and the necessity of liver transplantation (1-3). PBC occurs between the ages of 35-70 and affects predominantly women (1, 4).
Antimitochondrial antibodies (AMA), which are present in 90-96% of patients, are the most characteristic of this entity and can be observed long before the disease is clinically overt (5, 6). In addition, epitopes of T cells and B cells targeting mitochondrial autoantigens have been identified (7, 8).
Antinuclear antibodies may be also detected in about 50% of patients and they are relevant as a tool for diagnosis of PBC, specially in AMA-negative patients and their high specificity for PBC has been confirmed in several reports (9-11). They are directed against three components of the nuclear envelope (NE): the lamina, the pore complex (NPC) and the inner membrane (10-12). Remarkable is the high specificity of anti-NPCs antibodies for PBC, which appears to be greater than 95%. Therefore, the presence of anti-NPC antibodies can be used to confirm the diagnosis of PBC in atypical cases, especially when AMA are undetectable (11-13).
The large geographical differences in the frequency of PBC and regional difference in AMA and anti-nuclear antibodies prevalence are explained by distinct immunogenetic background in the population of PBC patients (14, 15).
Antimitochondrial antibodies
The presence of autoantibodies in the serum of patients with primary biliary cirrhosis (PBC) were first suggested by Jan Mackay in 1958 (12). In the following years, PBC sera were found to manifest a characteristic pattern, when tested again animal tissues by indirect immunofluorescence (IIF) and the cytoplasmic target identified as the mitochondria. In the past 50 years an enormous number of experimental studies have focused on AMA, and numerous rewarding discoveries have been made.
There are nine subtypes of AMA, four of which have been involved in PBC, including anti-M2, anti-M4, anti-M8 and anti-M9. It has been demonstrated, that autoantigens recognized by anti-M2 are located in the inner membranes of mitochondria, whereas those recognized by anti-M4, anti-M8 and anti-M9 are located in the outer mitochondrial membranes. Anti-M9 can be detected in both anti-M2-positive and -negative PBC patients, while anti-M4 is only positive in the presence of anti-M2.
The target antigen M2 is attached to the inner mitochondrial membrane (13, 16, 17) and consists of five components (17). These components have been identified in the following years on molecular bases as subunits of the 2-oxo acid dehydrogenase complex of the inner mitochondrial membrane: the pyruvate dehydrogenase complex (PDC), the 2-oxoglutarate dehydrogenase complex and the branched-chain 2-oxo acid dehydrogenase complexes (18-20). Using an original expression vector, Gershwin first identified the cDNA encoding the 70 kDa mitochondrial antigen that led to the identification of E2 subunit of pyruvate dehydrogenase complex (PDC-E2) (21). Serum antimitochondrial antibodies react against members of the 2-oxo-acid dehydrogenase complexes (2-OADC) family, including PDC-E2, the E2 subunit of branched chain 2-oxo-acid dehydrogenase complex (BCOADC-E2), the E2 subunit of the oxoglutarate dehydrogenase complex (OGDC-E2),the dihydrolipoamide dehydrogenase (E3)-binding protein (E3BP), and the E1α subunit of pyruvate dehydrogenase complex (PDC-E1α) (22). Sera of histologically proven PBC cases react only with the antigens BCOADC or OGDC, but not with PDC-E2, in 4-13% (23,24). More recently, Gershwin, Leung, and colleagues created a recombinant fusion protein (MIT3), which includes the immunodominant portions of the 3 primary targets of AMA, E2 – subunits of the pyruvate dehydrogenase complex (PDC-E2), the branched-chain 2-oxo-acid dehydrogenase complex (BCOADC-E2) and the 2-oxo-glutarate dehydrogenase complex (OGDC-E2) (25).
The major M2-antigen which is recognized by nearly 90-96% of PBC sera is the E2 component of PDC.
By indirect immunofluorescence false-positive results are quite frequent and in many cases a more sensitive and specific confirmation test, such as immunoblotting or ELISA, is required. In studies of AMA reactivity in large numbers of sera, Leung et al. have demonstrated that recombinant antigens used for immunodiagnosis are strikingly specific for PBC. Specificity and sensitivity is dramatically increased with the use of ELISA and/or immunoblot assays compared with immunofluorescence (28). Recently, it has been suggested that Luminex and an ELISA using a mixture of purified PDC and MIT3 as antigenic targets may increase sensitivity of the AMA detection systems (26, 27).
AMA positivity is considered specific for PBC, indeed it is one of the three diagnostic criteria for the disease. No proof of a pathogenic role for AMA has been obtained thus far. It is not clear how autoantibodies directed against a ubiquitous antigen might in turn produce a highly tissue-specific autoimmune injury. Studies of AMA-M2-positive individuals with initially no evidence of cholestatic liver disease of whom the majority developed fully manifested PBC over time additionally indicated that these autoantibodies may indeed be sufficiently specific very early markers development of PBC (28-30). Metcalf et al. reported that about 75% of asymptomatic individuals with serum AMA eventually developed symptoms of PBC over a 10-25-year observation period (29). Serum AMA strongly suggest the diagnosis of PBC at early stages even before the appearing of biochemical cholestasis. Although highly specific, AMA do not predict the prognosis in patients with PBC (30). Study of stored sera of well-characterized PBC patients followed for 7-28 years indicate that AMA levels are not associated with disease severity and progression (28).
Furthermore, AMA will typically reappear in patients transplanted for PBC but histological features of PBC re-manifest in few cases (31).
M4 is a single antigen with molecular weight of 52 kDa. Anti-M4 is found predominantly in patients with histological features of chronic active hepatitis and PBC. Recent studies have identified the major proteins in the M4 fraction which is related to the PDC-E1 subunits and sulphite oxidase (32-37). Anti-M8 has been found only in coexistence with anti-M2, the presence of anti-M8 indicates progressive disease activity. On the other hand, not all anti-M2-positive patients have anti-M8 (34, 38). Anti-M9 antibody is detected predominantly in patients with asymptomatic and early PBC, and it also can be positive in anti-M2-negative PBC patients. Patients with only anti-M9 have all the typical biochemical features found in classic anti-M2-positive patients, but seem to have slower disease progression and benign outcome, whereas patients having complement-fixing antibodies against anti-M2, anti-M4, and anti-M8 seem to have more active disease and worse outcome (34, 36, 37), though this finding wasn’t supported by a blinded study on Dutch PBC patients conducted by Vleggaar et al (39).
The exact role played by AMA in the immunopathology and pathogenesis of PBC remains elusive. However, current data indicate that the destruction of biliary cells is mediated by liver-infiltrating autoreactive T cells specific for the dominant PDC-E2 autoantigen (40-43).
AMA are non-organ- and non-species-specific, and contain IgA, IgG and IgM subclasses. Some studies have demonstrated that the different AMA IgG subclasses have different clinical significance (44).
Several possible mechanisms have been suggested regarding the generation of AMA, such as oxidative damage, molecular mimicry and changed biliary epithelial cell (BEC) apoptosis (45, 46).
Approximately 5% of well-documented PBC patients do not react with any of the mitochondrial antigens using currently available assays.
Antinuclear antibodies
Nuclear envelope protein autoantibodies

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1. Kaplan MM, Gershwin ME: Primary biliary cirrhosis. N Engl J Med 2005; 353: 1261-1273.
2. Prince M, Chetwynd A, Newman W et al.: Survival and symptom progression in a geographically based cohort of patients with primary biliary cirrhosis: follow – up to 28 years. Gastroenterology 2002; 123: 1044-1051.
3. Watt FE, James OF, Jones DEJ: Paterns of autoimmunity in primary biliary cirrhosis patients and their families: a population-based cohort study. QJMed 2004; 97: 397-406.
4. Talwalkar JA, Lindor KD. Primary biliary cirrhosis. Lancet 2003; 362: 53-61.
5. Miyakawa H, Tanaka A, Kikuchi K et al.: Detection of antimitochondrial autoantibodies in immunofluorescentAMA-negative patients with primary biliary cirrhosis usingrecombinant oantigens. Hepatology 2001; 34: 243-248.
6. Muratori L, Granito A, Muratori P et al.: Antimitochondrial antibodies and other antibodies in primary biliary cirrhosis: Diagnostic and prognostic value. Clin Liver Dis 2008; 12; 261-276.
7. Kita H: Autoreactive CD8-secific T-cells response in primary biliary cirrhosis. Hepatol Res 2007; 37 Suppl 3: S402-S405.
8. Ichiki Y, Shimoda S, Hara H et al.: Analysis of T-cell receptor beta of the T-cells clones reactiveto the human PDC- E2 163-176 peptidein the context of HLA-DR53 in patients with primary cirrhosis. Hepatology 1997; 26: 728-733.
9. Shimoda S, Nakamura M, Ishibashi H et al.: Molecular mimicry of mitochondrial and nuclear autoantigens in primary biliary cirrhosis. Gastroenterology 2003; 124: 1915-1925.
10. Muratori P, Muratori L, Ferrari R et al.: Characterization and clinical impact of antinuclear antibodies in primary biliary cirrhosis. Am J Gastroenterol 2003; 98:431-437.
11. Invernizzi P, Podda M, Battezzati P et al.: Autoantibodies against nuclear pore complexes are associated with more active and severe liver disease in primary biliary cirrhosis. J Hepatol 2001; 34: 366-72.
12. Worman HJ: Nuclear envelope protein autoantigens in primary biliary cirrhosis. Hepatology Research 2007; 37: S406-S411.
13. Berg PA, Klein R, Lindenborn-Fotinos J, Klöppel W: ATPase-associated antigen (M2): marker antigen for serological diagnosis of primary biliary cirrhosis. Lancet 1982; 2: 1423-1426.
14. Metcalf J, James O: The geoepidemiology of primary biliary cirrhosis. Semin Liver Dis 1997; 1: 13-22.
15. Invernizzi P, Battezzati P, Crosignani A et al.: Peculiar HLA polymorphism in Italian patients with primary biliary cirrhosis. J Hepatol 2003; 38: 401-406.
16. Lindenborn-Fotinos J, Sayers TJ, Berg PA: Mitochondrial antibodies in primary biliary cirrhosis. VI. Association of the complement fixing antigen with a component of the mitochondrial F1-ATPase complex. Clin Exp Immunol 1982; 50: 267-274.
17. Lindenborn-Fotinos J, Baum H, Berg PA: Mitochondrial antibodies in primary biliary cirrhosis: species and nonspecies specific determinants of M2 antigen. Hepatology 1985; 5: 763-769.
18. Mackay IR, Whittingham S, Fida S et al.: The peculiar autoimmunity of primary biliary cirrhosis. Immunol Rev 2000; 174: 226-237.
19. Van de Water J, Gershwin ME, Leung P et al.: The autoepitope of the 74-kD mitochondrial autoantigen of primary biliary cirrhosis corresponds to the functional site of dihydrolipoamide acetyltransferase. J Exp Med 1988; 167: 1791-1799.
20. Yeaman SJ: The 2-oxo acid dehydrogenase complexes: recent advances. Biochem J 1989; 257: 625-632.
21. Vergani D, Bogdanos DP: Positive markers in AMA-negative PBC. Am J. Gastroenterol 2003; 98 (2): 241-3.
22. Gershwin ME, Mackay IR, Sturgess A, Coppel RL: Identification and specificity of cDNA encoding the 70kd mitochondrial antigen recognized in primary biliary cirrhosis. J Immunol 1987; 138 (10): 3525-31.
23. Bassendine MF, Jones DE, Yeaman SJ: Biochemistry and autoimmune response to the 2-oxoacid dehydrogenase complexes in primary biliary cirrhosis. Semin Liver Dis 1997; 17: 49-60.
24. Leung RL, Coppel A, Ansari S et al.: Antimitochondrial antibodies in primary biliary cirrhosis. Semin Liver Dis 1997; 17: 61-69.
25. Muratori L, Muratori P, Granito A et al.: The Western immunoblotting pattern of anti-mitochondrial antibodies is independent of the clinical expression of primary biliary cirrhosis. Dig Liver Dis 2005; 37: 108-112.
26. Fussey SP, Ali ST, Guest JR et al.: Reactivity of primary biliary cirrhosis sera with Escherichia coli dihydrolipoamide acetyltransferase (E2p): characterization of the main immunogenic region. Proc Natl Acad Sci USA 1990; 87: 3987-3991.
27. Koike K, Ishibashi H, Koike M: Immunoreactivity of porcine heart dihydrolipoamide acetyl- and succinyl-transferases (PDC-E2, OGDC-E2) with primary biliary cirrhosis sera: characterization of the autoantigenic region and effects of enzymatic delipoylation and relipoylation. Hepatology 1998; 27:1 467-1474.
28. Moteki S, Leung PS, Coppel RL et al.: Use of a designer triple expression hybrid clone for three different lipoyl domain for the detection of antimitochondrial autoantibodies. Hepatology 1996; 24: 97-103.
29. Mackay IR: Primary biliary cirrhosis showing a high titer of autoantibody; report of a case. NEJM 1958; 258 (4): 185-8.
30. Oertelt S, Rieger R, Selmi C et al.: A sensitive bead assay for antimitochondrial antibodies: chipping away at AMA-negative primary biliary cirrhosis. Hepatology 2007; 45: 659-665.
31. Dahnrich C, Pares A, Caballeria L et al.: New ELISA for detecting primary biliary cirrhosis-specific antimitochondrial antibodies. Clin Chem 2009; 55: 978-985.
32. Bogdanos DB, Baum H, Vergani D: Antimitochondrial and other autoantibodies. Clin Liver Dis 2003; 7 (4): 759-77.
33. Metcalf JV, Mitchison HC, Palmer JM et al.: Natural history of early primary biliary cirrhosis. Lancet 1996; 348 (9039): 1399-4026.
34. Joshi F, Cauch-Dudek K, Heathcote EJ et al.: Antimitochondrial antibody profiles: Are they valid prognostic indicators in primary biliary cirrhosis? Am J Gastroenterol 2002; 97 (4): 999-1002.
35. Neuberger J, Thomson R: PBC and AMA-what is the connection? Hepatology 1999; 29: 271-276.
36. Berg CP, Stein GM, Klein R et al.: Demonstration of PDC-E1 subunits as major antigens in the complement-fixing fraction M4 and re-evaluation of PDC-E1-specific antibodies in PBC patients. Liver Int 2006; 26: 846-855.
37. Preuss B, Berg C, Altenberend F et al.: Demonstration of autoantibodies to recombinant human sulphite oxidase in patients with chronic liver disorders and analysis of their clinical relevance. Clin Exp Immunol 2007; 150: 312-321.
38. Weber P, Brenner J, Stechemesser E et al.: Characterization and clinical relevance of a new complement-fixing antibody--anti-M8-in patients with primary biliary cirrhosis. Hepatology 1986; 6: 553-559.
39. Vleggaar FP, van Buuren HR: No prognostic significance of antimitochondrial antibody profile testing in primary biliary cirrhosis. Hepatogastroenterology 2004; 51: 937-940.
40. Shimoda S, Van de Water J, Ansari A et al.: Identification and precursor frequency analysis of a common T cell epitope motif in mitochondrial autoantigens in primary biliary cirrhosis. J Clin Invest 1998; 102: 1831-1840.
41. Lleo A, Selmi C, Invernizzi P et al.: The consequences of apoptosis in autoimmunity. J Autoimmun 2008; 31: 257-262.
42. Shigematsu H, Shimoda S, Nakamura M et al.: Fine specificity of T cells reactive to human PDC-E2 163-176 peptide, the immunodominant autoantigen in primary biliary cirrhosis: implications for molecular mimicry and cross-recognition among mitochondrial autoantigens. Hepatology 2000; 32: 901-9.
43. Shimoda S, Nakamura M, Shigematsu H et al.: Mimicry peptides of human PDC-E2 163-176 peptide, the immunodominant T cell epitope of primary biliary cirrhosis. Hepatology 2000; 31: 1212-1
44. Rigopoulou E, Davies E, Bogdanos D et al.: Antimitochondrial antibodies of immunoglobulin G3 subclass are associated with a more severe disease course in primary bilary cirrhosis. Liver Int 2007; 27: 126-31.
45. Berg PA, Klein R: Mitochondrial antigen/antibody systems in primary biliary cirrhosis: revisited. Liver 1995; 15: 281-292.
46. Klein R, Pointner H, Zilly W et al.: Antimitochondrial antibody profiles in primary biliary cirrhosis distinguish at early stages between a benign and a progressive course: a prospective study on 200 patients followed for 10 years. Liver 1997; 17: 119-128.
47. 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. Journal of Autoimmunity 2003; 20 (3): 247-54.
48. Worman H, Courvalin J: Antinuclear antibodies specific for primary biliary cirrhosis. Autoimmunity Rev 2003; 2: 211-217.
49. Bauer A, Habior A: Measurement of gp210 autoantibodies in sera of patients with primary biliary cirrhosis. JCLA 2007; 21: 227-231.
50. 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 2005; 42: 386-392.
51. Starr CM, D’Onofrio M, Park MK, Hanover JA: Primary sequence and heterologous expression of nuclear pore glycoprotein p62. J Cell Bio. 1990; 110 (6): 1861-71.
52. Invernizzi P, Selmi C, Ranftler C et al.: Antinuclear antibodies in primary biliary cirrhosis. Semin Liver Dis 2005; 25 (3): 298-310.
53. Wesierska-Gadek J, Hohenuer H, Hitchman E, Penner E: Autoantibodies against nucleoporin p62 constitute a novel marker of primary biliary cirrhosis. Gastroenterology 1996; 110: 840-847.
54. Worman, HJ, Yuan J, Blobel G, Georgatos SD: Proc. Natl Acad Sci USA 1988; 85: 8531.
55. Courvalin JC, Lassoused K, Worman HJ, Blobel G: Identification and characterization of antibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J Exp Med 1990; 172: 961-967.
56. Nakamura M, Kondo H, Mori T et al.: Anti-gp210 and anticentromere antibodies are different risk factors for the progression of primary biliary cirrhosis. Hepatology 2007; 45: 118-27.
57. Yang W, Yu J, Nakajima A et al.: Do antinuclear antibodies in primary biliary cirrhosis patients identify increased risk for liver failure? Clin Gastroenterol Hepatol 2004; 2: 1116-1122.
58. Muratori P, Muratori L, Cassani F et al.: Anti-multiple nuclear dots (anti-MND) and anti Sp100 antibodies in hepatic and rheumatological disorders. 2002; Clin Exp Immunol 127; 172-175.
59. Wesierska-Gadek J, Penner E, Battezzati P et al.: Correlation of initial autoantibody profile and clinical outcome in primary biliary cirrhosis. Hepatology 2006; 43: 1135-1144.
60. Nakamura M, Takii Y, Ito M et al.: Increased expression of nuclear envelope gp210 antigen in small bile ducts in primary biliary cirrhosis. J Autoimmun 2006; 26: 138-45.
61. Wesierska-Gadek J, Penner E, Battezzati PM et al.: Correlation of initial autoantibody profile and clinica outcome in primary biliary cirrhosis. Hepatology 2006; 43: 1135-44.
62. Miyachi K, et al.: A male patient who developed late-onset primary biliary cirrhosis presenting with antinuclear envelope antibodies. Mod Rheumatol 2002; 12: 246-49.
63. Courvalin J, Lassoued K, Bartnik E et al.: The 210kDa nuclear envelope polypeptyde recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. J Clin Invest 1990; 86: 279-285.
64. Wesierska-Gadek J, Klima A, Komina O et al.: Characterization of autoantibodies against components of the nuclear pore complex, high frequency of anti-p62 nucleoporin antibodies. Ann NY Acad Sci 2007; 1109: 519-30.
65. Szostecki C, Will H, Netter HJ, Guldner HH: Autoantibodies to the nuclearSp100 protein in primary biliary cirrhosis and associated diseases: epitope specificity and immunoglobulin class distribution. 1992; Scand J Immunol; 36: 555-564.
66. Muratori P, Muratori L, Gershwin ME et al.: True antimitochondrial antibody-negative primary biliary cirrhosis, low sensitivity of the routine assays, or both? Clin Exp Immunol 2004; 135: 154-158.
67. Lozano F, Pares A, Borche L et al.: Autoantibodies against nuclear envelope-associated proteins in primary biliary cirrhosis. Hepatology 1988; 8: 930-938.
68. Szostecki C, Guldner H, Will H: Autoantibodies against “nuclear dots” in primary biliary cirrhosis. Semin Liver Dis 1997; 17: 71-78.
69. Remmel T, Piirsoo A, Koiveer A et al.: Clinical significance of different antinuclear antibodies patterns in the course of primary biliary cirrhosis. Gastroenterology 1996; 43: 1135-1140.
70. Zuchner D, Sternsdorf T, Szostecki C et al.: Prevalence, kinetics, and therapeutic modulation of autoantibodies against Sp100 and promyelocytic leukemia protein in a large cohort of patients with primary biliary cirrhosis. Hepatology1997; 26: 1123-1130.
71. Szostecki C, Guldner HH, Will H: Autoantibodies against “nuclear dots” in primary biliary cirrhosis. Semin Liver Dis 1997; 17: 71-78.
72. Czaja AJ, Norman GL: Autoantibodies in the diagnosis and management of liver disease. J Clin Gastroenterol 2003; 37, 315-29.
73. Romero-Gomez M et al.: Serum immunological profile in patients with chronic autoimmune cholestasis. Am J Gastroenterol 2004; 99, 2150-57.
74. Granito A, Yang W, Muratori L et al.: PML Nuclear body component Sp140 is a novel autoantigen in primary biliary cirrhosis. Am J Gastroenterol 2010; 105: 125-131.
75. Parveen S, Morshed SA, Nishioka M: High prevalence of antibodies to recombinant reactivities. J Gastroenterol Hepatol 1995; 10: 438-45.
otrzymano: 2011-09-12
zaakceptowano do druku: 2011-10-17

Adres do korespondencji:
*Alicja Bauer
Zakład Biochemii i Biologii Molekularnej Centrum Medyczne Kształcenia Podyplomowego
ul. Marymoncka 99, 01-813 Warszawa
tel.: (22) 569-38-28

Postępy Nauk Medycznych 11/2011
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