Volume 4, Issue 1, June 2020, Page: 1-10
Ro-autoantibody System and Characterisation of Protein Isoforms of Ro60 in Systemic Erythematosus Lupus (An Update)
Manideep Chowdary Pachva, Department of Molecular Genetics, Bangor University, Bangor, United Kingdom
Received: Feb. 3, 2020;       Accepted: Feb. 24, 2020;       Published: May 11, 2020
DOI: 10.11648/j.jcebe.20200401.11      View  301      Downloads  73
Abstract
Systemic lupus erythematosus (SLE) is a multisystem inflammatory and autoimmune disorder that usually affects various self-tissues of the body, whose sera is predominantly reported to have autoantibodies against Ro60 or TROVE-2 protein. Ro60 is a ring-shaped RNA-binding protein, that usually binds misfolded non-coding RNAs, pre-5S rRNA, and several small cytoplasmic RNA molecules known as Y RNAs (hY-RNAs). Y RNAs are known to be involved in regulating cellular stress responses and also in initiation of chromosomal replication. Ro60 is known to have 6 isoforms along with the short isoform. Recent studies of Ro60 protein in mammalian cells suggests that Ro60 is vital for the cell survival after the UV irradiation. It is evident that Ro60 is essential for degrading the damaged RNA due to the UV irradiation, because exposure to the UV irradiation might result in RNA: RNA and RNA: Protein crosslinks. Also, role of Ro60 in maintaining the tolerance is supported by the experiment which resulted in development of lupus like syndrome in the Ro60 knock-down mice by producing antibodies against chromatin and ribosomes. Thus, it is evident from the various studies that Ro60 is inevitably important for the cells and tissues for preventing the autoimmunity. This review focusses on the pathology and autoantibody system in SLE, structure and functions of the Ro60 in association with Y RNAs, and epitope bindings of Ro60 to the anti-Ro positive sera from SLE patients.
Keywords
Self-tolerance, Systemic Lupus Erythematosus, Ro60 Protein, Y RNAs, Anti-Ro Autoantibodies
To cite this article
Manideep Chowdary Pachva, Ro-autoantibody System and Characterisation of Protein Isoforms of Ro60 in Systemic Erythematosus Lupus (An Update), Journal of Chemical, Environmental and Biological Engineering. Vol. 4, No. 1, 2020, pp. 1-10. doi: 10.11648/j.jcebe.20200401.11
Copyright
Copyright © 2020 Authors retain the copyright of this article.
This article is an open access article distributed under the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Reference
[1]
Kuby, J., Goldsby, R. A., Kindst, J., and Osborne, B.. (2007). Kuby Immunology 7th edition (New York: W. H. Freeman).
[2]
Smith, D. A., and Germolec, D. R. (1999). Introduction to immunology and autoimmunity. Environ. Health Perspect. 107, 661–665.
[3]
Parkin, J., and Cohen, B. (2001). An overview of the immune system. Lancet Lond. Engl. 357, 1777–1789.
[4]
Chaplin, D. D. (2006). 1. Overview of the human immune response. J. Allergy Clin. Immunol. 117, S430–S435.
[5]
Chaplin, D. D. (2003). 1. Overview of the immune response. J. Allergy Clin. Immunol. 111, S442–S459.
[6]
Beutler, B., Hoebe, K., Du, X., and Ulevitch, R. J. (2003). How we detect microbes and respond to them: the Toll-like receptors and their transducers. J. Leukoc. Biol. 74, 479–485.
[7]
Goodnow, C. C., Sprent, J., de St Groth, B. F., and Vinuesa, C. G. (2005). Cellular and genetic mechanisms of self tolerance and autoimmunity. Nature 435, 590–597.
[8]
Xing, Y., and Hogquist, K. A. (2012). T-Cell Tolerance: Central and Peripheral. Cold Spring Harb. Perspect. Biol. 4.
[9]
Lorber, M., Gershwin, M. E., and Shoenfeld, Y. (1994). The coexistence of systemic lupus erythematosus with other autoimmune diseases: the kaleidoscope of autoimmunity. Semin. Arthritis Rheum. 24, 105–113.
[10]
Pohl, D., and Benseler, S. (2013). Chapter 131 - Systemic inflammatory and autoimmune disorders. In Handbook of Clinical Neurology, M. L. and H. B. S. Olivier Dulac, ed. (Elsevier), pp. 1243–1252.
[11]
Suárez-Fueyo, A., Bradley, S. J., and Tsokos, G. C. (2016). T cells in Systemic Lupus Erythematosus. Curr. Opin. Immunol. 43, 32–38.
[12]
Manson, J. J., and Rahman, A. (2006). Systemic lupus erythematosus. Orphanet J. Rare Dis. 1, 6.
[13]
Liu, Z., and Davidson, A. (2012). Taming lupus-a new understanding of pathogenesis is leading to clinical advances. Research Gate 18, 871–882.
[14]
Flesher, D. L. T., Sun, X., Behrens, T. W., Graham, R. R., and Criswell, L. A. (2010). Recent advances in the genetics of systemic lupus erythematosus. Expert Rev. Clin. Immunol. 6, 461–479.
[15]
Gaffney, P. M., Moser, K. L., Graham, R. R., and Behrens, T. W. (2002). Recent advances in the genetics of systemic lupus erythematosus. Rheum. Dis. Clin. North Am. 28, 111–126.
[16]
Schur, P. H. (1995). Genetics of systemic lupus erythematosus. Lupus 4, 425–437.
[17]
Bauer, J. W., Baechler, E. C., Petri, M., Batliwalla, F. M., Crawford, D., Ortmann, W. A., Espe, K. J., Li, W., Patel, D. D., Gregersen, P. K., et al. (2006). Elevated serum levels of interferon-regulated chemokines are biomarkers for active human systemic lupus erythematosus. PLoS Med. 3, e491.
[18]
Gilliet, M., Cao, W., and Liu, Y.-J. (2008). Plasmacytoid dendritic cells: sensing nucleic acids in viral infection and autoimmune diseases. Nat. Rev. Immunol. 8, 594–606.
[19]
COJOCARU, M., COJOCARU, I. M., SILOSI, I., and VRABIE, C. D. (2011). Manifestations of Systemic Lupus Erythematosus. Mædica 6, 330–336.
[20]
Dema, B., and Charles, N. (2016). Autoantibodies in SLE: Specificities, Isotypes and Receptors. Antibodies 5, 2.
[21]
Tan, E. M. (1989). Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv. Immunol. 44, 93–151.
[22]
Yaniv, G., Twig, G., Shor, D. B.-A., Furer, A., Sherer, Y., Mozes, O., Komisar, O., Slonimsky, E., Klang, E., Lotan, E., et al. (2015). A volcanic explosion of autoantibodies in systemic lupus erythematosus: a diversity of 180 different antibodies found in SLE patients. Autoimmun. Rev. 14, 75–79.
[23]
Li, J., Leng, X., Li, Z., Ye, Z., Li, C., Li, X., Zhu, P., Wang, Z., Zheng, Y., Li, X., et al. (2014). Chinese SLE treatment and research group registry: III. association of autoantibodies with clinical manifestations in Chinese patients with systemic lupus erythematosus. J. Immunol. Res. 2014, 809389.
[24]
Conrad, K., Roggenbuck, D., Reinhold, D., and Sack, U. (2012). Autoantibody diagnostics in clinical practice. Autoimmun. Rev. 11, 207–211.
[25]
Arbuckle, M. R., McClain, M. T., Rubertone, M. V., Scofield, R. H., Dennis, G. J., James, J. A., and Harley, J. B. (2003). Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 349, 1526–1533.
[26]
Sim, S., Yao, J., Weinberg, D. E., Niessen, S., Yates, J. R., and Wolin, S. L. (2012). The zipcode-binding protein ZBP1 influences the subcellular location of the Ro 60-kDa autoantigen and the noncoding Y3 RNA. RNA 18, 100–110.
[27]
Wolin, S. L., and Reinisch, K. M. (2006). The Ro 60 kDa autoantigen comes into focus: Interpreting epitope mapping experiments on the basis of structure. Autoimmun. Rev. 5, 367–372.
[28]
Yoshimi, R., Ueda, A., Ozato, K., and Ishigatsubo, Y. (2012). Clinical and Pathological Roles of Ro/SSA Autoantibody System. J. Immunol. Res. 2012, e606195.
[29]
Hung, T., Pratt, G., Sundararaman, B., Townsend, M. J., Chaivorapol, C., Bhangale, T., Graham, R. R., Ortmann, W., Criswell, L. A., Yeo, G., et al. (2015). The Ro60 Autoantigen Binds Endogenous Retroelements and Regulates Inflammatory Gene Expression. Science 350, 455–459.
[30]
Stein, A. J., Fuchs, G., Fu, C., Wolin, S. L., and Reinisch, K. M. (2005). Structural Insights into RNA Quality Control: The Ro Autoantigen Binds Misfolded RNAs via Its Central Cavity. Cell 121, 529–539.
[31]
Ben-Chetrit, E., Gandy, B. J., Tan, E. M., and Sullivan, K. F. (1989). Isolation and characterization of a cDNA clone encoding the 60-kD component of the human SS-A/Ro ribonucleoprotein autoantigen. J. Clin. Invest. 83, 1284–1292.
[32]
Scofield, R. H., Kurien, B. T., Gross, J. K., Reed, N. B., Taylor, A. K., Dominguez, N., Mehta, P., Guthridge, J. M., and Bachmann, M. (2004). Interaction of calcium and Ro60: increase of antigenicity. Mol. Immunol. 41, 809–816.
[33]
Smith, S., Ní Gabhann, J., McCarthy, E., Coffey, B., Mahony, R., Byrne, J. C., Stacey, K., Ball, E., Bell, A., Cunnane, G., et al. (2014). Estrogen receptor α regulates tripartite motif-containing protein 21 expression, contributing to dysregulated cytokine production in systemic lupus erythematosus. Arthritis Rheumatol. Hoboken NJ 66, 163–172.
[34]
Liu, Y., Snow, B. E., Hande, M. P., Baerlocher, G., Kickhoefer, V. A., Yeung, D., Wakeham, A., Itie, A., Siderovski, D. P., Lansdorp, P. M., et al. (2000). Telomerase-associated protein TEP1 is not essential for telomerase activity or telomere length maintenance in vivo. Mol. Cell. Biol. 20, 8178–8184.
[35]
Papa, L., Akinyi, L., Liu, M. C., Pineda, J. A., Tepas, J. J., Oli, M. W., Zheng, W., Robinson, G., Robicsek, S. A., Gabrielli, A., et al. (2010). Ubiquitin C-terminal hydrolase is a novel biomarker in humans for severe traumatic brain injury. Crit. Care Med. 38, 138–144.
[36]
Kowalski, M. P., and Krude, T. (2015). Functional roles of non-coding Y RNAs. Int. J. Biochem. Cell Biol. 66, 20–29.
[37]
Lerner, M. R., Boyle, J. A., Hardin, J. A., and Steitz, J. A. (1981). Two novel classes of small ribonucleoproteins detected by antibodies associated with lupus erythematosus. Science 211, 400–402.
[38]
Maraia, R., Sakulich, A. L., Brinkmann, E., and Green, E. D. (1996). Gene encoding human Ro-associated autoantigen Y5 RNA. Nucleic Acids Res. 24, 3552–3559.
[39]
Teunissen, S. W., Kruithof, M. J., Farris, A. D., Harley, J. B., Venrooij, W. J., and Pruijn, G. J. (2000). Conserved features of Y RNAs: a comparison of experimentally derived secondary structures. Nucleic Acids Res. 28, 610–619.
[40]
Christov, C. P., Trivier, E., and Krude, T. (2008). Noncoding human Y RNAs are overexpressed in tumours and required for cell proliferation. Br. J. Cancer 98, 981–988.
[41]
Deutscher, S. L., Harley, J. B., and Keene, J. D. (1988). Molecular analysis of the 60-kDa human Ro ribonucleoprotein. Proc. Natl. Acad. Sci. U. S. A. 85, 9479–9483.
[42]
McCauliffe, D. (1997). Cutaneous diseases in adults associated with Anti-Ro/SS-A autoantibody production. Lupus 6, 158–166.
[43]
Mond, C. B., Peterson, M. G., and Rothfield, N. F. (1989). Correlation of anti-Ro antibody with photosensitivity rash in systemic lupus erythematosus patients. Arthritis Rheum. 32, 202–204.
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