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

Scandinavian Journal of Immunology - Tập 42 Số 2 - Trang 257-268 - 1995
Thomas Sternsdorf1, H H Guldner1, Carin Szostecki1, Thilo Grötzinger1, Hans Will1
1Heinrich‐Pette Institute of Experimental Virology and Immunology at the University of Hamburg, Hamburg, Germany

Tóm tắt

The nucleoproteins Sp100 and PML, the first an autoantigen predominant in patients with primary biliary cirrhosis (PBC) and the second a transformation and cell growth suppressing protein aberrantly expressed in promyelocytic leukaemia ceils, were recently shown to colocalize in dot‐like nuclear domains. Here we analysed whether PML, like Sp100, is also an autoantigen in patients with PBC and other autoimmune diseases, and whether both proteins interact directly. Testing sera from autoimmune patients using an immunoprecipitation assay with radiolabelled PML and an immunofluorescence assay based on a cell hne overexpressing PML, autoantibodies (Aabs) against PML were found in the majority of anti‐Sp100 Aab positive patients. Only very few patients with PBC or other autoimmune diseases contained anti‐PML or anti‐Sp100 Aabs exclusively. In contrast to Sp100, immunoreactivity of recombinant PML in immunoblots was only weak and was directed to one region. This suggests that anti‐PML Aabs recognize fewer and preferentially conformation‐dependent epitopes. In an immuno precipitation assay using in vitro synthesized Sp 100 and PML proteins and Abs to recombinant proteins, no direct interaction was observed. Taken together, these data indicate that Aabs against PML are as highly prevalent and specific for patients with PBC as those against Sp100. The colocalization of these autoantigens and the frequent co‐occurence of the corresponding Aabs might reflect an association of both proteins mediated by one or several other proteins.

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Tài liệu tham khảo

Vierling JM, 1990, Hepatology: A Textbook of Liver Disease, 1158

10.1016/0168-8278(91)90903-O

Bernstein RM, 1984, Diversity of autoantibodies in primary biliary cirrhosis and chronic active hepatitis, Clin Exp Immunol, 55, 553

10.1016/S0140-6736(84)90164-8

10.1016/S0309-1651(05)80021-9

10.1083/jcb.112.5.785

10.1016/0092-8674(94)90341-7

10.1016/0092-8674(94)90340-9

10.1016/0962-8924(93)90214-L

Szostecki C, 1987, Autoimmune sera recognize a 100 kD nuclear protein antigen (Sp100), Clin Exp Immunol, 68, 108

10.4049/jimmunol.145.12.4338

10.1111/j.1365-3083.1992.tb03224.x

10.1002/art.1780340614

10.1111/j.1365-2249.1991.tb05630.x

10.4049/jimmunol.149.12.4067

10.1182/blood.V82.6.1858.1858

10.1099/0022-1317-74-12-2679

10.1099/0022-1317-75-6-1223

Maul GG, 1994, HSV‐1 IE Protein Vmw110 causes redistribution of PML, Embo J, 13, 5062, 10.1002/j.1460-2075.1994.tb06835.x

10.1038/347558a0

10.1016/0092-8674(91)90112-C

10.1126/science.1720570

10.1002/j.1460-2075.1994.tb06356.x

Breitman TR, 1981, Terminal differentiation of promyelocytic leucaemia cells in response to retinoic acid, Blood, 57, 1000, 10.1182/blood.V57.6.1000.1000

10.1128/MCB.14.10.6858

10.1007/BF00192686

10.1016/0092-8674(91)90356-4

Lambert V, 1990, Virus‐neutralizing monoclonal antibody to a conserved epitope on the duck hepatitis B virus pre‐S protein, J Virol, 64, 1290, 10.1128/jvi.64.3.1290-1297.1990

10.1073/pnas.89.12.5547

10.1007/BF00286991

10.1016/0092-8674(91)90113-D

Stemler M, 1990, Mapping of B‐cell epitopes of the human hepatitis B virus X protein, J Virol, 64, 2802, 10.1128/jvi.64.6.2802-2809.1990

Sambrook J, 1989, Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory, 18.26

10.1073/pnas.76.9.4350

Guldner HH, 1988, Epitope mapping with a recombinant human 68‐kDa (Ul) ribonucleoprotein antigen reveals heterogeneous autoantibody profiles in human autoimmune sera, J Immunol, 141, 469, 10.4049/jimmunol.141.2.469

10.1136/jcp.38.7.801

10.1136/jcp.40.2.232

10.1016/0950-3528(87)90053-4

10.1159/000412228

Prost AC, 1987, Comparing HEp‐2 cell line with rat liver in routine screening test for anti‐nuclear and anti‐ nucleolar autoantibodies in autoimmune diseases, Ann Biol Clin, 45, 610

10.1002/hep.1840160121

Szostecki C, 1994, Die humorale Autoimmun‐antwort gegen das nukleäre Sp100 Autoantigen in Patienten mit primär biliärer Zirrhose, Z ärztl Fortbild, 88, 573

10.1002/art.1780290401

10.1016/S0065-2776(08)60641-0

10.1073/pnas.90.24.12010

Mamula MJ, 1994, B cells process and present lupus autoaniigens that initiate autoimmune T cell responses, J Immunol, 152, 1453, 10.4049/jimmunol.152.3.1453

10.1007/BF02205547

Epstein AL, 1984, Immunobiochemical characterization with monoclonal antibodies of Epstein‐Barr virus‐associated eariy antigens in chemically induced cells, J Virol, 50, 372, 10.1128/jvi.50.2.372-379.1984

10.1242/jcs.101.4.773

10.1128/MCB.13.10.6170

Fagioli M, 1992, Alternative splicing of PML transcripts predicts coexpression of several carboxy‐term‐inally diiferent protein isoforms, Oncogene, 7, 1083

10.1006/bbrc.1993.2100

10.1016/S0140-6736(84)91108-5

10.1002/hep.1840140305

10.1016/S0016-5085(94)95333-3