Two Nuclear Dot‐Associated Proteins, PML and SplOO, are Often Co‐Autoimmunogenic in Patients with Primary Biliary Cirrhosis

Sternsdorf, Thomas; Guldner, H. H.; Szostecki, Carin; Grötzinger, Thilo; Will, Hans

doi:10.1111/j.1365-3083.1995.tb03652.x

Cited by 123 publications

(94 citation statements)

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“…The antibody has also been detected in patients with AMA -negative PBC and thus is considered a useful marker for serological diagnosis of PBC 40) . The anti -PML antibody has been detected in PBC patients positive for anti -Sp100 antibody, and patients positive for these antibodies have been shown to show faster progression of PBC than those negative for these antibodies 41,42) . In the present study, however, the prevalence of each of these antibodies among patients negative for AMA -M2 and M2 -E3 was only 6.3% and was seldom correlated with laboratory test results.…”

Section: Discussionmentioning

confidence: 99%

Autoantibodies by Line Immunoassay in Patients With Primary Biliary Cirrhosis

Saito¹,

Takahashi²,

Abe³

et al. 2012

Fukushima J. Med. Sci.

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: Objectives : We attempted to measure multiple autoantibodies simultaneously using line immunoassay (LIA) in patients with primary biliary cirrhosis (PBC) with or without anti -mitochondrial antibody (AMA) and patients with PBC -autoimmune hepatitis (AIH) overlap, and we examined the clinical significance of measuring these autoantibodies. Methods : The study population consisted of 80 patients with PBC (including 12 AMA -negative patients), 16 patients with PBC -AIH overlap and 40 patients with AIH as controls. Nine antibodies (AMA -M2, M2 -3E, Sp100, PML, gp210, Ro -52, LKM -1, LC -1 and SLA/LP) were detected by LIA, and AMA -M2 and anti -centromere antibody (ACA) were detected by ELISA. We examined the relationship between these autoantibodies and clinical findings. Results : The positive prevalence of each autoantibody and ACA in the PBC group, as determined by LIA, was as follows : 13.8% for anti -Sp100, 8.7% for anti -PML, 40% for anti -gp210 and 27.5% for anti -Ro -52 antibodies and 32.5% for ACA. In the PBC -AIH overlap group, the prevalence of anti -gp210 antibody (68.7%) and that of anti -Ro -52 antibody (81.2%) were significantly higher than those in the PBC and AIH groups. Only a few patients were positive for 2 or more autoantibodies. Nine patients were determined to be negative for all autoantibodies by LIA, of whom 7 were positive for ACA. Patients positive for anti -gp210 antibody included more patients classified as stage 4 on histology than did the negative group. Those positive for ACA included more patents with varices than did the negative group. Conclusion : LIA can measure multiple autoantibodies simultaneously and thus is considered useful in diagnosing PBC and PBC -AIH overlap. In addition, ACA is a useful marker for identifying AMA -negative PBC.

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Section: Discussionmentioning

confidence: 99%

Autoantibodies by Line Immunoassay in Patients With Primary Biliary Cirrhosis

Saito¹,

Takahashi²,

Abe³

et al. 2012

Fukushima J. Med. Sci.

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“…Since PML has transcription factor-like structural features [Borden et al, 1995;Goddard et al, 1991;Reddy et al, 19921, it may be that it is part of a protein complex that is associated with DNA. Another protein of this complex is the human auto-immune antigen SplOO [Sternsdorf et al, 1995;Szostecki et al, 19901. These observations are consistent with the idea that PML bodies, as visualized by fluorescence microscopy and electron microscopy [Stuurman et al, 19921, are protein complexes associated with specific loci of the human genome, possibly affecting the transcriptional activity of these loci, resulting in late replication. Interaction with the PML-RARa fusion protein may disrupt the protein complex and change the activity of the loci to which PML bodies are associated, resulting in AF'L.…”

Section: Discussionmentioning

confidence: 99%

PML-containing nuclear bodies: Their spatial distribution in relation to other nuclear components

et al. 1996

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PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components Grande, M.A.; van der Kraan, K.; van Steensel, B.; Schul, W.; de The, H.; van der Voort, H.T.M.; de Jong, L.; van Driel, R. Link to publicationCitation for published version (APA): Grande, M. A., van der Kraan, K., van Steensel, B., Schul, W., de The, H., van der Voort, H. T. M., ... van Driel, R. (1996). PML-containing nuclear bodies: their spatial distribution in relation to other nuclear components. Journal of Cellular Biochemistry, 63, 280-291. 3.0.CO;2-T" class="link">https://doi.org/10.1002/(SICI)1097-4644(19961201)63:33.0.CO;2-T General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. The PML protein is a human growth suppressor concentrated in 10 to 20 nuclear bodies per nucleus (PML bodies). Disruption of the PML gene has been shown to be related to acute promyelocytic leukaemia (APL). To obtain information about the function of PML bodies we have investigated the 3D-distribution of PML bodies in the nucleus of T24 cells and compared it with the spatial distribution of a variety of other nuclear components, using fluorescence dual-labeling immunocytochemistry and confocal microscopy. Results show that PML bodies are not enriched in nascent RNA, the splicing component U2-snRNP, or transcription factors (glucocorticoid receptor, 'TFIIH, and E2F). These results show that PML bodies are not prominent sites of RNA synthesis or RNA splicing. We found that a large fraction of PML bodies (50 to 80%) is closely associated with DNA replication domains during exclusively middle-late S-phase. Furthermore, in most cells that we analysed we found at least one PML body was tightly associated with a coiled body. In the APL cell line NB4, the PML gene is fused with the RARa gene due to a chromosomal rearrangement. PML bodies have disappeared and the PML antigen, i.e., PML and the PML-RAR fusion protcin, is dispersed in a punctated pattern throughout the nucleoplasm. We showed that in NB4 cells the sites that are rich in PML antigen significantly colocalize with sites at which nascent RNA accumulates. This suggests that, in contrast to non-APL cells, in NB4 cells the PML antigen is associated with sites of transcription. The implications of these findings for the function of PML bod...

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“…In addition to AMAs, which are the hallmark of PBC, antinuclear antibodies (ANAs) have also been detected in 30% of PBC patients [8][9][10] . Two PBC-specific ANA immunofluorescence patterns have been identified [11,12] : "multiple nuclear dots", corresponding to the antigens Sp100 and Sp140, promyelocytic leukemia (PML) nuclear body proteins and small ubiquitin-like modifiers (SUMOs) [13,14] , and "nuclear membrane" (rim), caused by anti-nuclear envelope antibodies (ANEAs), such as gp210 and nucleoporin p62 [15,16] . The anti-gp210 antibodies are highly specific for PBC and are associated with disease activity and severity [17,18] .…”

Section: Introductionmentioning

confidence: 99%