The immunobiology of Ro52 (TRIM21) in autoimmunity: A critical review

Journal of Autoimmunity

Volumn 39, Issue 1-2, 2012, Pages 77-82

  Oke, Vilija ^a   Wahren Herlenius, Marie ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

Author keywords

Autoantibodies; Autoantigen; Autoimmunity; CLE; Interferon; Ro52; Sj gren's syndrome; SLE; TRIM21

Indexed keywords

AUTOANTIBODY; B CELL ACTIVATING FACTOR; LA ANTIBODY; PROTEIN; PROTEIN ANTIBODY; RITUXIMAB; RO ANTIBODY; RO52 AUTOANTIBODY; RO52 PROTEIN; UNCLASSIFIED DRUG;

APOPTOSIS; AUTOIMMUNE HEPATITIS; AUTOIMMUNITY; CELL COMPARTMENTALIZATION; CELL CYCLE; CONGENITAL HEART BLOCK; HUMAN; IMMUNOBIOLOGY; IMMUNOREGULATION; INTERSTITIAL LUNG DISEASE; MYOSITIS; NONHUMAN; PHOTOSENSITIVITY; PRIMARY BILIARY CIRRHOSIS; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN MOTIF; PROTEIN STRUCTURE; REVIEW; SJOEGREN SYNDROME; SYSTEMIC LUPUS ERYTHEMATOSUS; SYSTEMIC SCLEROSIS;

ANIMALS; AUTOIMMUNE DISEASES; AUTOIMMUNITY; HUMANS; INTERFERON REGULATORY FACTOR-3; INTERFERON REGULATORY FACTOR-7; INTERFERON REGULATORY FACTORS; RIBONUCLEOPROTEINS; UBIQUITINATION;

EID: 84862496763     PISSN: 08968411     EISSN: 10959157     Source Type: Journal    
DOI: 10.1016/j.jaut.2012.01.014     Document Type: Review

References (86)

1. Popovic K., Wahren-Herlenius M., Nyberg F. Clinical follow-up of 102 anti-Ro/SSA-positive patients with dermatological manifestations. Acta Derm Venereol 2008, 88:370-375.
2. Eriksson C., Kokkonen H., Johansson M., Hallmans G., Wadell G., Rantapaa-Dahlqvist S. Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden. Arthritis Res Ther 2011, 13:R30.
3. Ben-Chetrit E., Chan E.K., Sullivan K.F., Tan E.M. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med 1988, 167:1560-1571.
4. Chan E.K., Hamel J.C., Buyon J.P., Tan E.M. Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen. J Clin Invest 1991, 87:68-76.
5. Itoh K., Itoh Y., Frank M.B. Protein heterogeneity in the human Ro/SSA ribonucleoproteins. the 52- and 60-kD Ro/SSA autoantigens are encoded by separate genes. J Clin Invest 1991, 87:177-186.
6. Schulte-Pelkum J., Fritzler M., Mahler M. Latest update on the Ro/SS-A autoantibody system. Autoimmun Rev 2009, 8:632-637.
7. Sontheimer R.D., Maddison P.J., Reichlin M., Jordon R.E., Stastny P., Gilliam J.N. Serologic and HLA associations in subacute cutaneous lupus erythematosus, a clinical subset of lupus erythematosus. Ann Intern Med 1982, 97:664-671.
8. Salomonsson S., Dzikaite V., Zeffer E., Eliasson H., Ambrosi A., Bergman G., et al. A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block. Scand J Immunol 2011, 74:511-517.
9. Salomonsson S., Dorner T., Theander E., Bremme K., Larsson P., Wahren-Herlenius M. A serologic marker for fetal risk of congenital heart block. Arthritis Rheum 2002, 46:1233-1241.
10. Popovic K., Brauner S., Ek M., Wahren-Herlenius M., Nyberg F. Fine specificity of the Ro/SSA autoantibody response in relation to serological and clinical findings in 96 patients with self-reported cutaneous symptoms induced by the sun. Lupus 2007, 16:10-17.
11. Ghillani P., Andre C., Toly C., Rouquette A.M., Bengoufa D., Nicaise P., et al. Clinical significance of anti-Ro52 (TRIM21) antibodies non-associated with anti-SSA 60kDa antibodies: results of a multicentric study. Autoimmun Rev 2011, 10:509-513.
12. Venables P.J. Sjogren's syndrome. Best Pract Res Clin Rheumatol 2004, 18:313-329.
13. Hanly J.G., Su L., Farewell V., Fritzler M.J. Comparison between multiplex assays for autoantibody detection in systemic lupus erythematosus. J Immunol Methods 2010, 358:75-80.
14. Rutjes S.A., Vree Egberts W.T., Jongen P., Van Den Hoogen F., Pruijn G.J., Van Venrooij W.J. Anti-Ro52 antibodies frequently co-occur with anti-Jo-1 antibodies in sera from patients with idiopathic inflammatory myopathy. Clin Exp Immunol 1997, 109:32-40.
15. Montano-Loza A.J., Shums Z., Norman G.L., Czaja A.J. Prognostic implications of antibodies to Ro/SSA and soluble liver antigen in type 1 autoimmune hepatitis. Liver Int 2011, Official Journal of the International Association for the Study of the Liver.
16. Koenig M., Fritzler M.J., Targoff I.N., Troyanov Y., Senecal J.L. Heterogeneity of autoantibodies in 100 patients with autoimmune myositis: insights into clinical features and outcomes. Arthritis Res Ther 2007, 9:R78.
17. Marie I., Hatron P.Y., Dominique S., Cherin P., Mouthon L., Menard J.F., et al. Short-term and long-term outcome of anti-Jo1-positive patients with anti-Ro52 antibody. Semin Arthritis Rheum 2011.
18. Bozic B., Pruijn G.J., Rozman B., van Venrooij W.J. Sera from patients with rheumatic diseases recognize different epitope regions on the 52-kD Ro/SS-A protein. Clin Exp Immunol 1993, 94:227-235.
19. Ottosson L., Hennig J., Espinosa A., Brauner S., Wahren-Herlenius M., Sunnerhagen M. Structural, functional and immunologic characterization of folded subdomains in the Ro52 protein targeted in Sjogren's syndrome. Mol Immunol 2006, 43:588-598.
20. Reymond A., Meroni G., Fantozzi A., Merla G., Cairo S., Luzi L., et al. The tripartite motif family identifies cell compartments. EMBO J 2001, 20:2140-2151.
21. Nisole S., Stoye J.P., Saib A. TRIM family proteins: retroviral restriction and antiviral defence. nature reviews. Microbiol 2005, 3:799-808.
22. Yap M.W., Nisole S., Lynch C., Stoye J.P. Trim5alpha protein restricts both HIV-1 and murine leukemia virus. Proc Natl Acad Sci U S A 2004, 101:10786-10791.
23. McNab F.W., Rajsbaum R., Stoye J.P., O'Garra A. Tripartite-motif proteins and innate immune regulation. Curr Opinn Immunol 2011, 23:46-56.
24. Espinosa A., Zhou W., Ek M., Hedlund M., Brauner S., Popovic K., et al. The Sjogren's syndrome-associated autoantigen Ro52 is an E3 ligase that regulates proliferation and cell death. J Immunol 2006, 176:6277-6285.
25. Hershko A., Heller H., Elias S., Ciechanover A. Components of ubiquitin-protein ligase system. resolution, affinity purification, and role in protein breakdown. J Biol Chem 1983, 258:8206-8214.
26. Clague M.J., Urbe S. Ubiquitin: same molecule, different degradation pathways. Cell 2010, 143:682-685.
27. Plafker S.M., Plafker K.S., Weissman A.M., Macara I.G. Ubiquitin charging of human class III ubiquitin-conjugating enzymes triggers their nuclear import. J Cell Biol 2004, 167:649-659.
28. Wada K., Kamitani T. Autoantigen Ro52 is an E3 ubiquitin ligase. Biochem Biophys Res Commun 2006, 339:415-421.
29. Kong H.J., Anderson D.E., Lee C.H., Jang M.K., Tamura T., Tailor P., et al. Cutting edge: autoantigen Ro52 is an interferon inducible E3 ligase that ubiquitinates IRF-8 and enhances cytokine expression in macrophages. J Immunol 2007, 179:26-30.
30. Higgs R., Lazzari E., Wynne C., Ni Gabhann J., Espinosa A., Wahren-Herlenius M., et al. Self protection from anti-viral responses-Ro52 promotes degradation of the transcription factor IRF7 downstream of the viral Toll-like receptors. PLoS One 2010, 5:e11776.
31. Higgs R., Ni Gabhann J., Ben Larbi N., Breen E.P., Fitzgerald K.A., Jefferies C.A. The E3 ubiquitin ligase Ro52 negatively regulates IFN-beta production post-pathogen recognition by polyubiquitin-mediated degradation of IRF3. J Immunol 2008, 181:1780-1786.
32. Espinosa A., Dardalhon V., Brauner S., Ambrosi A., Higgs R., Quintana F.J., et al. Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway. J Exp Med 2009, 206:1661-1671.
33. Yang K., Shi H.X., Liu X.Y., Shan Y.F., Wei B., Chen S., et al. TRIM21 is essential to sustain IFN regulatory factor 3 activation during antiviral response. J Immunol 2009, 182:3782-3792.
34. Sabile A., Meyer A.M., Wirbelauer C., Hess D., Kogel U., Scheffner M., et al. Regulation of p27 degradation and S-phase progression by Ro52 RING finger protein. Mol Cell Biol 2006, 26:5994-6004.
35. Ishii T., Ohnuma K., Murakami A., Takasawa N., Yamochi T., Iwata S., et al. SS-A/Ro52, an autoantigen involved in CD28-mediated IL-2 production. J Immunol 2003, 170:3653-3661.
36. Rhodes D.A., Ihrke G., Reinicke A.T., Malcherek G., Towey M., Isenberg D.A., et al. The 52 000 MW Ro/SS-A autoantigen in Sjogren's syndrome/systemic lupus erythematosus (Ro52) is an interferon-gamma inducible tripartite motif protein associated with membrane proximal structures. Immunol 2002, 106:246-256.
37. Keeble A.H., Khan Z., Forster A., James L.C. TRIM21 is an IgG receptor that is structurally, thermodynamically, and kinetically conserved. Proc Natl Acad Sci U S A 2008, 105:6045-6050.
38. Espinosa A., Oke V., Elfving A., Nyberg F., Covacu R., Wahren-Herlenius M. The autoantigen Ro52 is an E3 ligase resident in the cytoplasm but enters the nucleus upon cellular exposure to nitric oxide. Exp Cell Res 2008, 314:3605-3613.
39. Nobuhara Y., Kawano S., Kageyama G., Sugiyama D., Saegusa J., Kumagai S. Is SS-A/Ro52 a hydrogen peroxide-sensitive signaling molecule?. Antioxid Redox Signal 2007, 9:385-391.
40. Strandberg L., Ambrosi A., Espinosa A., Ottosson L., Eloranta M.L., Zhou W., et al. Interferon-alpha induces up-regulation and nuclear translocation of the Ro52 autoantigen as detected by a panel of novel Ro52-specific monoclonal antibodies. J Clin Immunol 2008, 28:220-231.
41. Harbers M., Nomura T., Ohno S., Ishii S. Intracellular localization of the Ret finger protein depends on a functional nuclear export signal and protein kinase C activation. J Biol Chem 2001, 276:48596-48607.
42. Wen W., Meinkoth J.L., Tsien R.Y., Taylor S.S. Identification of a signal for rapid export of proteins from the nucleus. Cell 1995, 82:463-473.
43. Chan E.K., Di Donato F., Hamel J.C., Tseng C.E., Buyon J.P. 52-kD SS-A/Ro: genomic structure and identification of an alternatively spliced transcript encoding a novel leucine zipper-minus autoantigen expressed in fetal and adult heart. J Exp Med 1995, 182:983-992.
44. Nakken B., Jonsson R., Bolstad A.I. Polymorphisms of the Ro52 gene associated with anti-Ro 52-kd autoantibodies in patients with primary Sjogren's syndrome. Arthritis Rheum 2001, 44:638-646.
45. Gottenberg J.E., Cagnard N., Lucchesi C., Letourneur F., Mistou S., Lazure T., et al. Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjogren's syndrome. Proc Natl Acad Sci U S A 2006, 103:2770-2775.
46. Baechler E.C., Batliwalla F.M., Karypis G., Gaffney P.M., Ortmann W.A., Espe K.J., et al. Interferon-inducible gene expression signature in peripheral blood cells of patients with severe lupus. Proc Natl Acad Sci U S A 2003, 100:2610-2615.
47. Lundberg I.E., Helmers S.B. The type I interferon system in idiopathic inflammatory myopathies. Autoimmun 2010, 43:239-243.
48. Weckerle C.E., Franek B.S., Kelly J.A., Kumabe M., Mikolaitis R.A., Green S.L., et al. Network analysis of associations between serum interferon alpha activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum 2010.
49. Yoshimi R., Chang T.H., Wang H., Atsumi T., Morse H.C., Ozato K. Gene disruption study reveals a nonredundant role for TRIM21/Ro52 in NF-kappaB-dependent cytokine expression in fibroblasts. J Immunol 2009, 182:7527-7538.
50. Abbas A.K. Cellular and molecular immunology 2007, Saunders Elsevier, , Philadelphia. 6th ed.
51. Munir M. TRIM proteins: another class of viral victims. Sci Signal 2010, 3:jc2.
52. Nordmark G., Alm G.V., Ronnblom L. Mechanisms of disease: primary Sjogren's syndrome and the type I interferon system. Nat Clin Pract Rheumatol 2006, 2:262-269.
53. Theofilopoulos A.N., Baccala R., Beutler B., Kono D.H. Type I interferons (alpha/beta) in immunity and autoimmunity. Annu Rev Immunol 2005, 23:307-336.
54. Thibault D.L., Chu A.D., Graham K.L., Balboni I., Lee L.Y., Kohlmoos C., et al. IRF9 and STAT1 are required for IgG autoantibody production and B cell expression of TLR7 in mice. J Clin Invest 2008, 118:1417-1426.
55. Klippel J.H. Primer on the rheumatic diseases 2008, Springer. 13th ed. J.H. Klippel (Ed.).
56. Mok M.Y. The immunological basis of B-cell therapy in systemic lupus erythematosus. Int J Rheum Dis 2010, 13:3-11.
57. Bohnhorst J.O., Bjorgan M.B., Thoen J.E., Natvig J.B., Thompson K.M. Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center founder cells in healthy individuals and disturbance in the B cell subpopulations in patients with primary Sjogren's syndrome. J Immunol 2001, 167:3610-3618.
58. Bohnhorst J.O., Thoen J.E., Natvig J.B., Thompson K.M. Significantly depressed percentage of CD27+ (memory) B cells among peripheral blood B cells in patients with primary Sjogren's syndrome. Scand J Immunol 2001, 54:421-427.
59. Groom J.R., Fletcher C.A., Walters S.N., Grey S.T., Watt S.V., Sweet M.J., et al. BAFF and MyD88 signals promote a lupuslike disease independent of T cells. J Exp Med 2007, 204:1959-1971.
60. Vallerskog T., Heimburger M., Gunnarsson I., Zhou W., Wahren-Herlenius M., Trollmo C., et al. Differential effects on BAFF and APRIL levels in rituximab-treated patients with systemic lupus erythematosus and rheumatoid arthritis. Arthritis Res Ther 2006, 8:R167.
61. Quartuccio L., Fabris M., Moretti M., Barone F., Bombardieri M., Rupolo M., et al. Resistance to rituximab therapy and local BAFF overexpression in Sjogren's syndrome-related myoepithelial sialadenitis and low-grade parotid B-cell lymphoma. Open Rheumatol J 2008, 2:38-43.
62. Jonsdottir T., Gunnarsson I., Risselada A., Henriksson E.W., Klareskog L., van Vollenhoven R.F. Treatment of refractory SLE with rituximab plus cyclophosphamide: clinical effects, serological changes, and predictors of response. Ann Rheum Dis 2008, 67:330-334.
63. Dall'Era M., Wofsy D. Connective tissue diseases: belimumab for systemic lupus erythematosus: breaking through?. Nat Rev Rheumatol 2010, 6:124-125.
64. Crispin J.C., Tsokos G.C. Interleukin-17-producing T cells in lupus. Curr Opin Rheumatol 2010, 22:499-503.
65. Garrett-Sinha L.A., John S., Gaffen S.L. IL-17 and the Th17 lineage in systemic lupus erythematosus. Curr Opin Rheumatol 2008, 20:519-525.
66. Yang J., Chu Y., Yang X., Gao D., Zhu L., Wan L., et al. Th17 and natural Treg cell population dynamics in systemic lupus erythematosus. Arthritis Rheum 2009, 60:1472-1483.
67. Tanasescu C., Balanescu E., Balanescu P., Olteanu R., Badea C., Grancea C., et al. IL-17 in cutaneous lupus erythematosus. Eur J Intern Med 2010, 21:202-207.
68. Katsifis G.E., Rekka S., Moutsopoulos N.M., Pillemer S., Wahl S.M. Systemic and local interleukin-17 and linked cytokines associated with Sjogren's syndrome immunopathogenesis. Am J Pathol 2009, 175:1167-1177.
69. Hennig J., Ottosson L., Andresen C., Horvath L., Kuchroo V.K., Broo K., et al. Structural organization and Zn2+-dependent subdomain interactions involving autoantigenic epitopes in the ring-B-box-coiled-coil (RBCC) region of Ro52. J Biol Chem 2005, 280:33250-33261.
70. Itoh Y., Kriet J.D., Reichlin M. Organ distribution of the Ro (SS-A) antigen in the guinea pig. Arthritis Rheum 1990, 33:1815-1821.
71. Ioannides D., Golden B.D., Buyon J.P., Bystryn J.C. Expression of SS-A/Ro and SS-B/La antigens in skin biopsy specimens of patients with photosensitive forms of lupus erythematosus. Arch Dermatol 2000, 136:340-346.
72. Ohlsson M., Jonsson R., Brokstad K.A. Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjogren's syndrome. Scand J Immunol 2002, 56:456-469.
73. Bolstad A.I., Eiken H.G., Rosenlund B., Alarcon-Riquelme M.E., Jonsson R. Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjogren's syndrome. Arthritis Rheum 2003, 48:174-185.
74. Oke V., Vassilaki I., Espinosa A., Strandberg L., Kuchroo V.K., Nyberg F., et al. High Ro52 expression in spontaneous and UV-induced cutaneous inflammation. J Invest Dermatol 2009, 129:2000-2010.
75. Lee H.J., Sinha A.A. Cutaneous lupus erythematosus: understanding of clinical features, genetic basis, and pathobiology of disease guides therapeutic strategies. Autoimmun 2006, 39:433-444.
76. Saegusa J., Kawano S., Koshiba M., Hayashi N., Kosaka H., Funasaka Y., et al. Oxidative stress mediates cell surface expression of SS-A/Ro antigen on keratinocytes. Free Radic Biol Med 2002, 32:1006-1016.
77. Casciola-Rosen L., Rosen A. Ultraviolet light-induced keratinocyte apoptosis: a potential mechanism for the induction of skin lesions and autoantibody production in LE. Lupus 1997, 6:175-180.
78. Lawley W., Doherty A., Denniss S., Chauhan D., Pruijn G., van Venrooij W.J., et al. Rapid lupus autoantigen relocalization and reactive oxygen species accumulation following ultraviolet irradiation of human keratinocytes. Rheumatol (Oxford) 2000, 39:253-261.
79. Munoz L.E., Lauber K., Schiller M., Manfredi A.A., Herrmann M. The role of defective clearance of apoptotic cells in systemic autoimmunity. Nat Rev Rheumatol 2010, 6:280-289.
80. Baumann I., Kolowos W., Voll R.E., Manger B., Gaipl U., Neuhuber W.L., et al. Impaired uptake of apoptotic cells into tingible body macrophages in germinal centers of patients with systemic lupus erythematosus. Arthritis Rheum 2002, 46:191-201.
81. Ronnblom L., Alm G.V., Eloranta M.L. Type I interferon and lupus. Curr Opin Rheumatol 2009, 21:471-477.
82. Rhodes B., Vyse T.J. The genetics of SLE: an update in the light of genome-wide association studies. Rheumatol 2008, 47:1603-1611.
83. Song J.S., Do J.H., Lee S.W. The prevalence and the clinical relevance of anti-Ro52 in Korean patients with primary Sjogren's syndrome. Rheumatol Int 2011.
84. Lee L.A., Frank M.B., McCubbin V.R., Reichlin M. Autoantibodies of neonatal lupus erythematosus. J Invest Dermatol 1994, 102:963-966.
85. Yoshimasu T., Hiroi A., Ohtani T., Uede K., Furukawa F. Comparison of anti 60 and 52 kDa SS-A/Ro antibodies in the pathogenesis of cutaneous lupus erythematosus. J Dermatol Sci 2002, 29:35-41.
86. Granito A., Muratori P., Muratori L., Pappas G., Cassani F., Worthington J., 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 2007, 26:831-838.