Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases
Abstract
:1. Introduction
2. Structure of Ro60
3. Ro60 in Quality Control and Cellular Distribution of Small RNAs
3.1. YRNAs
3.2. 5S rRNA
3.3. Alu and L1 Retroelement Transcripts
4. Ro60’s Role in RNA Editing
5. Ro60 RNP Complex and Its Extracellular Presentation
5.1. Components of the Ro60 RNP Autoantigen Complex
5.2. Ro60 RNP Complex Transportation and Delivery to Antigen-Presenting Cells (APCs)
6. Innate Immune Sensing of Ro60 RNP Complexes and Inflammation
6.1. Endosomal TLR-Mediated Responses
6.2. Activation of Inflammasomes
6.3. Ro60 Antigen Presentation to T Cells
6.4. B-Cell Activation by Ro60 RNP
7. Ro60 Autoantibodies in the Pathogenesis of Autoimmune Diseases
8. Ro60 Autoantibodies in the Diagnosis and Monitoring of Autoimmune Diseases
8.1. Clinical Laboratory Techniques for Anti-Ro60 Detection and Measurement
8.2. Use of Ro60 Serology in Diagnosis and Monitoring
9. Commensals, Ro60 Cross-Reactivity, and Autoimmunity
10. Conclusions and Future Perspectives
Author Contributions
Funding
Conflicts of Interest
References
- Radziszewska, A.; Webb, K.; Peckham, H.; Ioannou, Y. Ro60 Expression Decreases with Age in Peripheral Blood Mononuclear Cells of Children and Adolescents and Correlates with Tlr7 Stimulation in Pdcs of Prepubertal Children. Ann. Rheum. Dis. 2017, 76, 389. [Google Scholar] [CrossRef]
- Clancy, R.M.; Alvarez, D.; Komissarova, E.; Barrat, F.J.; Swartz, J.; Buyon, J.P. Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: A novel pathway to autoimmune-associated heart block. J. Immunol. 2010, 184, 2148–2155. [Google Scholar] [CrossRef] [PubMed]
- Hung, T.; Pratt, G.A.; Sundararaman, B.; Townsend, M.J.; Chaivorapol, C.; Bhangale, T.; Graham, R.R.; Ortmann, W.; Criswell, L.A.; Yeo, G.W.; et al. The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression. Science 2015, 350, 455–459. [Google Scholar] [CrossRef] [PubMed]
- O’Brien, C.A.; Wolin, S.L. A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors. Genes Dev. 1994, 8, 2891–2903. [Google Scholar] [CrossRef] [PubMed]
- Campos-Almaraz, M.; Fraire-Velazquez, S.; Moreno, J.; Herrera-Esparza, R. The 5S rRNA is associated with Ro60 ribonucleoprotein and is co-precipitated with hYRNAs by anti-Ro antibodies. Autoimmunity 1999, 31, 95–101. [Google Scholar] [CrossRef] [PubMed]
- Keene, J.D. RNA regulons: Coordination of post-transcriptional events. Nat. Rev. Genet. 2007, 8, 533–543. [Google Scholar] [CrossRef] [PubMed]
- Glisovic, T.; Bachorik, J.L.; Yong, J.; Dreyfuss, G. RNA-binding proteins and post-transcriptional gene regulation. FEBS Lett. 2008, 582, 1977–1986. [Google Scholar] [CrossRef] [PubMed]
- Bechara, R.; Vagner, S.; Mariette, X. Post-transcriptional checkpoints in autoimmunity. Nat. Rev. Rheumatol. 2023, 19, 486–502. [Google Scholar] [CrossRef]
- Bohnsack, K.E.; Yi, S.; Venus, S.; Jankowsky, E.; Bohnsack, M.T. Cellular functions of eukaryotic RNA helicases and their links to human diseases. Nat. Rev. Mol. Cell Biol. 2023, 24, 749–769. [Google Scholar] [CrossRef]
- Ferrer, J.; Dimitrova, N. Transcription regulation by long non-coding RNAs: Mechanisms and disease relevance. Nat. Rev. Mol. Cell Biol. 2024, 25, 396–415. [Google Scholar] [CrossRef]
- Nemeth, K.; Bayraktar, R.; Ferracin, M.; Calin, G.A. Non-coding RNAs in disease: From mechanisms to therapeutics. Nat. Rev. Genet. 2024, 25, 211–232. [Google Scholar] [CrossRef] [PubMed]
- Boire, G.; Craft, J. Human Ro ribonucleoprotein particles: Characterization of native structure and stable association with the La polypeptide. J. Clin. Investig. 1990, 85, 1182–1190. [Google Scholar] [CrossRef] [PubMed]
- Valkov, N.; Das, S. Y RNAs: Biogenesis, Function and Implications for the Cardiovascular System. Adv. Exp. Med. Biol. 2020, 1229, 327–342. [Google Scholar] [CrossRef] [PubMed]
- Langley, A.R.; Chambers, H.; Christov, C.P.; Krude, T. Ribonucleoprotein particles containing non-coding Y RNAs, Ro60, La and nucleolin are not required for Y RNA function in DNA replication. PLoS ONE 2010, 5, e13673. [Google Scholar] [CrossRef] [PubMed]
- Ramesh, A.; Savva, C.G.; Holzenburg, A.; Sacchettini, J.C. Crystal structure of Rsr, an ortholog of the antigenic Ro protein, links conformational flexibility to RNA binding activity. J. Biol. Chem. 2007, 282, 14960–14967. [Google Scholar] [CrossRef] [PubMed]
- Fuchs, G.; Stein, A.J.; Fu, C.; Reinisch, K.M.; Wolin, S.L. Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen. Nat. Struct. Mol. Biol. 2006, 13, 1002–1009. [Google Scholar] [CrossRef] [PubMed]
- Stein, A.J.; Fuchs, G.; Fu, C.; Wolin, S.L.; Reinisch, K.M. Structural insights into RNA quality control: The Ro autoantigen binds misfolded RNAs via its central cavity. Cell 2005, 121, 529–539. [Google Scholar] [CrossRef] [PubMed]
- Colombatti, A.; Bonaldo, P.; Doliana, R. Type A modules: Interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins. Matrix 1993, 13, 297–306. [Google Scholar] [CrossRef] [PubMed]
- Whittaker, C.A.; Hynes, R.O. Distribution and evolution of von Willebrand/integrin A domains: Widely dispersed domains with roles in cell adhesion and elsewhere. Mol. Biol. Cell 2002, 13, 3369–3387. [Google Scholar] [CrossRef]
- Bateman, A.; Kickhoefer, V. The TROVE module: A common element in Telomerase, Ro and Vault ribonucleoproteins. BMC Bioinform. 2003, 4, 49. [Google Scholar] [CrossRef]
- Rutjes, S.A.; Lund, E.; van der Heijden, A.; Grimm, C.; van Venrooij, W.J.; Pruijn, G.J. Identification of a novel cis-acting RNA element involved in nuclear export of hY RNAs. RNA 2001, 7, 741–752. [Google Scholar] [CrossRef] [PubMed]
- Kowalski, M.P.; Krude, T. Functional roles of non-coding Y RNAs. Int. J. Biochem. Cell Biol. 2015, 66, 20–29. [Google Scholar] [CrossRef] [PubMed]
- Wang, I.; Kowalski, M.P.; Langley, A.R.; Rodriguez, R.; Balasubramanian, S.; Hsu, S.T.; Krude, T. Nucleotide contributions to the structural integrity and DNA replication initiation activity of noncoding y RNA. Biochemistry 2014, 53, 5848–5863. [Google Scholar] [CrossRef] [PubMed]
- Mathews, M.B.; Francoeur, A.M. La antigen recognizes and binds to the 3’-oligouridylate tail of a small RNA. Mol. Cell. Biol. 1984, 4, 1134–1140. [Google Scholar] [CrossRef] [PubMed]
- Green, C.D.; Long, K.S.; Shi, H.; Wolin, S.L. Binding of the 60-kDa Ro autoantigen to Y RNAs: Evidence for recognition in the major groove of a conserved helix. RNA 1998, 4, 750–765. [Google Scholar] [CrossRef] [PubMed]
- Wolin, S.L.; Steitz, J.A. The Ro small cytoplasmic ribonucleoproteins: Identification of the antigenic protein and its binding site on the Ro RNAs. Proc. Natl. Acad. Sci. USA 1984, 81, 1996–2000. [Google Scholar] [CrossRef] [PubMed]
- Pruijn, G.J.; Slobbe, R.L.; van Venrooij, W.J. Analysis of protein—RNA interactions within Ro ribonucleoprotein complexes. Nucleic Acids Res. 1991, 19, 5173–5180. [Google Scholar] [CrossRef] [PubMed]
- Spurlock, C.F., 3rd; Tossberg, J.T.; Guo, Y.; Sriram, S.; Crooke, P.S., 3rd; Aune, T.M. Defective structural RNA processing in relapsing-remitting multiple sclerosis. Genome Biol. 2015, 16, 58. [Google Scholar] [CrossRef] [PubMed]
- Shi, H.; O’Brien, C.A.; Van Horn, D.J.; Wolin, S.L. A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens. RNA 1996, 2, 769–784. [Google Scholar]
- Hogg, J.R.; Collins, K. Human Y5 RNA specializes a Ro ribonucleoprotein for 5S ribosomal RNA quality control. Genes Dev. 2007, 21, 3067–3072. [Google Scholar] [CrossRef]
- Szymanski, M.; Zielezinski, A.; Barciszewski, J.; Erdmann, V.A.; Karlowski, W.M. 5SRNAdb: An information resource for 5S ribosomal RNAs. Nucleic Acids Res. 2016, 44, D180–D183. [Google Scholar] [CrossRef] [PubMed]
- Deininger, P. Alu elements: Know the SINEs. Genome Biol. 2011, 12, 236. [Google Scholar] [CrossRef] [PubMed]
- Zinshteyn, B.; Nishikura, K. Adenosine-to-inosine RNA editing. Wiley Interdiscip. Rev. Syst. Biol. Med. 2009, 1, 202–209. [Google Scholar] [CrossRef] [PubMed]
- Savva, Y.A.; Rieder, L.E.; Reenan, R.A. The ADAR protein family. Genome Biol. 2012, 13, 252. [Google Scholar] [CrossRef] [PubMed]
- Vlachogiannis, N.I.; Tual-Chalot, S.; Zormpas, E.; Bonini, F.; Ntouros, P.A.; Pappa, M.; Bournia, V.K.; Tektonidou, M.G.; Souliotis, V.L.; Mavragani, C.P.; et al. Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis. J. Autoimmun. 2021, 125, 102755. [Google Scholar] [CrossRef] [PubMed]
- Li, Q.; Gloudemans, M.J.; Geisinger, J.M.; Fan, B.; Aguet, F.; Sun, T.; Ramaswami, G.; Li, Y.I.; Ma, J.B.; Pritchard, J.K.; et al. RNA editing underlies genetic risk of common inflammatory diseases. Nature 2022, 608, 569–577. [Google Scholar] [CrossRef] [PubMed]
- Tariq, A.; Garncarz, W.; Handl, C.; Balik, A.; Pusch, O.; Jantsch, M.F. RNA-interacting proteins act as site-specific repressors of ADAR2-mediated RNA editing and fluctuate upon neuronal stimulation. Nucleic Acids Res. 2013, 41, 2581–2593. [Google Scholar] [CrossRef] [PubMed]
- Quinones-Valdez, G.; Tran, S.S.; Jun, H.I.; Bahn, J.H.; Yang, E.W.; Zhan, L.; Brummer, A.; Wei, X.; Van Nostrand, E.L.; Pratt, G.A.; et al. Regulation of RNA editing by RNA-binding proteins in human cells. Commun. Biol. 2019, 2, 19. [Google Scholar] [CrossRef] [PubMed]
- Vlachogiannis, N.I.; Gatsiou, A.; Silvestris, D.A.; Stamatelopoulos, K.; Tektonidou, M.G.; Gallo, A.; Sfikakis, P.P.; Stellos, K. Increased adenosine-to-inosine RNA editing in rheumatoid arthritis. J. Autoimmun. 2020, 106, 102329. [Google Scholar] [CrossRef]
- Vasudevan, A.A.; Smits, S.H.; Hoppner, A.; Haussinger, D.; Koenig, B.W.; Munk, C. Structural features of antiviral DNA cytidine deaminases. Biol. Chem. 2013, 394, 1357–1370. [Google Scholar] [CrossRef]
- Gallois-Montbrun, S.; Kramer, B.; Swanson, C.M.; Byers, H.; Lynham, S.; Ward, M.; Malim, M.H. Antiviral protein APOBEC3G localizes to ribonucleoprotein complexes found in P bodies and stress granules. J. Virol. 2007, 81, 2165–2178. [Google Scholar] [CrossRef] [PubMed]
- Mavragani, C.P.; Kirou, K.A.; Nezos, A.; Seshan, S.; Wild, T.; Wahl, S.M.; Moutsopoulos, H.M.; Crow, M.K. Expression of APOBEC family members as regulators of endogenous retroelements and malignant transformation in systemic autoimmunity. Clin. Immunol. 2021, 223, 108649. [Google Scholar] [CrossRef] [PubMed]
- Fayyaz, A.; Kurien, B.T.; Scofield, R.H. Autoantibodies in Sjogren’s Syndrome. Rheum. Dis. Clin. N. Am. 2016, 42, 419–434. [Google Scholar] [CrossRef]
- Jones, E.L.; Laidlaw, S.M.; Dustin, L.B. TRIM21/Ro52—Roles in Innate Immunity and Autoimmune Disease. Front. Immunol. 2021, 12, 738473. [Google Scholar] [CrossRef] [PubMed]
- Clark, G.; Reichlin, M.; Tomasi, J.T.B. Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus. J. Immunol. 1969, 102, 117–122. [Google Scholar] [CrossRef] [PubMed]
- Juste-Dolz, A.; do Nascimento, N.M.; Monzo, I.; Grau-Garcia, E.; Roman-Ivorra, J.A.; Lopez-Paz, J.L.; Escorihuela, J.; Puchades, R.; Morais, S.; Gimenez-Romero, D.; et al. New structural insights into the role of TROVE2 complexes in the on-set and pathogenesis of systemic lupus erythematosus determined by a combination of QCM-D and DPI. Anal. Bioanal. Chem. 2019, 411, 4709–4720. [Google Scholar] [CrossRef] [PubMed]
- Scofield, R.H.; Kurien, B.T.; Gross, J.K.; Reed, N.B.; Taylor, A.K.; Dominguez, N.; Mehta, P.; Guthridge, J.M.; Bachmann, M. Interaction of calcium and Ro60: Increase of antigenicity. Mol. Immunol. 2004, 41, 809–816. [Google Scholar] [CrossRef] [PubMed]
- Kurien, B.T.; Bachmann, M.P. On-Membrane Renaturation of Recombinant Ro60 Autoantigen by Calcium Ions. Methods Mol. Biol. 2015, 1314, 255–261. [Google Scholar] [CrossRef] [PubMed]
- Kurien, B.T.; Porter, A.; Dorri, Y.; Iqbal, S.; D’Souza, A.; Singh, A.; Asfa, S.; Cartellieri, M.; Mathias, K.; Matsumoto, H.; et al. Degree of modification of Ro60 by the lipid peroxidation by-product 4-hydroxy-2-nonenal may differentially induce Sjogren syndrome or systemic lupus erythematosus in BALB/c mice. Free Radic. Biol. Med. 2011, 50, 1222–1233. [Google Scholar] [CrossRef]
- Reed, J.; Sim, S.; Wolin, S.; Clancy, R.M.; Buyon, J. Ro60 Requires Y3 RNA for Cell Surface Exposure and Inflammation Associated with Cardiac Manifestations of Neonatal Lupus. J. Immunol. 2013, 191, 110–116. [Google Scholar] [CrossRef]
- Gao, Y.; Qin, Y.; Wan, C.; Sun, Y.; Meng, J.; Huang, J.; Hu, Y.; Jin, H.; Yang, K. Small Extracellular Vesicles: A Novel Avenue for Cancer Management. Front. Oncol. 2021, 11, 638357. [Google Scholar] [CrossRef] [PubMed]
- Kapsogeorgou, E.K.; Abu-Helu, R.F.; Moutsopoulos, H.M.; Manoussakis, M.N. Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins. Arthritis Rheumatol. 2005, 52, 1517–1521. [Google Scholar] [CrossRef] [PubMed]
- Driedonks, T.A.P.; Mol, S.; de Bruin, S.; Peters, A.L.; Zhang, X.; Lindenbergh, M.F.S.; Beuger, B.M.; van Stalborch, A.D.; Spaan, T.; de Jong, E.C.; et al. Y-RNA subtype ratios in plasma extracellular vesicles are cell type- specific and are candidate biomarkers for inflammatory diseases. J. Extracell. Vesicles 2020, 9, 1764213. [Google Scholar] [CrossRef] [PubMed]
- Driedonks, T.A.P.; Nolte-’t Hoen, E.N.M. Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System. Front. Immunol. 2018, 9, 3164. [Google Scholar] [CrossRef] [PubMed]
- Cambier, L.; de Couto, G.; Ibrahim, A.; Echavez, A.K.; Valle, J.; Liu, W.; Kreke, M.; Smith, R.R.; Marban, L.; Marban, E. Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion. EMBO Mol. Med. 2017, 9, 337–352. [Google Scholar] [CrossRef] [PubMed]
- Chakrabortty, S.K.; Prakash, A.; Nechooshtan, G.; Hearn, S.; Gingeras, T.R. Extracellular vesicle-mediated transfer of processed and functional RNY5 RNA. RNA 2015, 21, 1966–1979. [Google Scholar] [CrossRef] [PubMed]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Rosen, A.; Casciola-Rosen, L.; Ahearn, J. Novel packages of viral and self-antigens are generated during apoptosis. J. Exp. Med. 1995, 181, 1557–1561. [Google Scholar] [CrossRef]
- Pan, Z.J.; Davis, K.; Maier, S.; Bachmann, M.P.; Kim-Howard, X.R.; Keech, C.; Gordon, T.P.; McCluskey, J.; Farris, A.D. Neo-epitopes are required for immunogenicity of the La/SS-B nuclear antigen in the context of late apoptotic cells. Clin. Exp. Immunol. 2006, 143, 237–248. [Google Scholar] [CrossRef]
- Reed, J.H.; Jackson, M.W.; Gordon, T.P. A B cell apotope of Ro 60 in systemic lupus erythematosus. Arthritis Rheum. 2008, 58, 1125–1129. [Google Scholar] [CrossRef]
- McArthur, C.; Wang, Y.; Veno, P.; Zhang, J.; Fiorella, R. Intracellular trafficking and surface expression of SS-A (Ro), SS-B (La), poly(ADP-ribose) polymerase and alpha-fodrin autoantigens during apoptosis in human salivary gland cells induced by tumour necrosis factor-alpha. Arch. Oral Biol. 2002, 47, 443–448. [Google Scholar] [CrossRef] [PubMed]
- Hizir, Z.; Bottini, S.; Grandjean, V.; Trabucchi, M.; Repetto, E. RNY (YRNA)-derived small RNAs regulate cell death and inflammation in monocytes/macrophages. Cell Death Dis. 2017, 8, e2530. [Google Scholar] [CrossRef] [PubMed]
- Barrat, F.J.; Meeker, T.; Chan, J.H.; Guiducci, C.; Coffman, R.L. Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms. Eur. J. Immunol. 2007, 37, 3582–3586. [Google Scholar] [CrossRef]
- Hon, K.L.; Leung, A.K. Neonatal lupus erythematosus. Autoimmune Dis. 2012, 2012, 301274. [Google Scholar] [CrossRef] [PubMed]
- Buyon, J.P.; Saxena, A.; Izmirly, P.M.; Cuneo, B.; Wainwright, B. Neonatal lupus: Clinical spectrum, biomarkers, pathogenesis, and approach to treatment. In Systemic Lupus Erythematosus, 2nd ed.; Elsevier: Amsterdam, The Netherlands, 2021; pp. 507–519. [Google Scholar] [CrossRef]
- Murakami, Y.; Fukui, R.; Tanaka, R.; Motoi, Y.; Kanno, A.; Sato, R.; Yamaguchi, K.; Amano, H.; Furukawa, Y.; Suzuki, H.; et al. Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes. Front. Immunol. 2021, 12, 777197. [Google Scholar] [CrossRef] [PubMed]
- Green, N.M.; Moody, K.S.; Debatis, M.; Marshak-Rothstein, A. Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands. J. Biol. Chem. 2012, 287, 39789–39799. [Google Scholar] [CrossRef] [PubMed]
- Guo, H.; Callaway, J.B.; Ting, J.P. Inflammasomes: Mechanism of action, role in disease, and therapeutics. Nat. Med. 2015, 21, 677–687. [Google Scholar] [CrossRef] [PubMed]
- Shin, J.I.; Lee, K.H.; Joo, Y.H.; Lee, J.M.; Jeon, J.; Jung, H.J.; Shin, M.; Cho, S.; Kim, T.H.; Park, S.; et al. Inflammasomes and autoimmune and rheumatic diseases: A comprehensive review. J. Autoimmun. 2019, 103, 102299. [Google Scholar] [CrossRef] [PubMed]
- Chen, B.; Wang, Y.; Chen, G. New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases. Nutrients 2023, 15, 4584. [Google Scholar] [CrossRef]
- Demarco, B.; Danielli, S.; Fischer, F.A.; Bezbradica, J.S. How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumatoid Arthritis. Cells 2022, 11, 1307. [Google Scholar] [CrossRef]
- Shaw, P.J.; McDermott, M.F.; Kanneganti, T.D. Inflammasomes and autoimmunity. Trends Mol. Med. 2011, 17, 57–64. [Google Scholar] [CrossRef] [PubMed]
- Kim, S.K.; Choe, J.Y.; Lee, G.H. Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjogren’s syndrome. Clin. Chim. Acta 2017, 474, 147–154. [Google Scholar] [CrossRef] [PubMed]
- Vakrakou, A.G.; Boiu, S.; Ziakas, P.D.; Xingi, E.; Boleti, H.; Manoussakis, M.N. Systemic activation of NLRP3 inflammasome in patients with severe primary Sjogren’s syndrome fueled by inflammagenic DNA accumulations. J. Autoimmun. 2018, 91, 23–33. [Google Scholar] [CrossRef] [PubMed]
- Verstappen, G.M.; Pringle, S.; Bootsma, H.; Kroese, F.G.M. Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis. Nat. Rev. Rheumatol. 2021, 17, 333–348. [Google Scholar] [CrossRef] [PubMed]
- Zhao, C.; Zhao, W. NLRP3 Inflammasome-A Key Player in Antiviral Responses. Front. Immunol. 2020, 11, 211. [Google Scholar] [CrossRef] [PubMed]
- Mu, X.; Ahmad, S.; Hur, S. Endogenous Retroelements and the Host Innate Immune Sensors. Adv. Immunol. 2016, 132, 47–69. [Google Scholar] [CrossRef] [PubMed]
- Tarallo, V.; Hirano, Y.; Gelfand, B.D.; Dridi, S.; Kerur, N.; Kim, Y.; Cho, W.G.; Kaneko, H.; Fowler, B.J.; Bogdanovich, S.; et al. DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88. Cell 2012, 149, 847–859. [Google Scholar] [CrossRef] [PubMed]
- Li, J.; Hu, L.; Liu, Y.; Huang, L.; Mu, Y.; Cai, X.; Weng, C. DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation. J. Immunol. 2015, 195, 5732–5749. [Google Scholar] [CrossRef] [PubMed]
- Mitoma, H.; Hanabuchi, S.; Kim, T.; Bao, M.; Zhang, Z.; Sugimoto, N.; Liu, Y.J. The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome. Immunity 2013, 39, 123–135. [Google Scholar] [CrossRef]
- Lee, J.; Mohammad, N.; Lu, Y.; Kang, K.; Han, K.; Brantly, M. Alu RNA induces NLRP3 expression through TLR7 activation in alpha-1-antitrypsin-deficient macrophages. JCI Insight 2022, 7, e158791. [Google Scholar] [CrossRef]
- Routsias, J.G.; Tzioufas, A.G.; Sakarellos-Daitsiotis, M.; Sakarellos, C.; Moutsopoulos, H.M. Epitope mapping of the Ro/SSA60KD autoantigen reveals disease-specific antibody-binding profiles. Eur. J. Clin. Investig. 1996, 26, 514–521. [Google Scholar] [CrossRef] [PubMed]
- McClain, M.T.; Heinlen, L.D.; Dennis, G.J.; Roebuck, J.; Harley, J.B.; James, J.A. Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry. Nat. Med. 2005, 11, 85–89. [Google Scholar] [CrossRef] [PubMed]
- Wolin, S.L.; Reinisch, K.M. The Ro 60 kDa autoantigen comes into focus: Interpreting epitope mapping experiments on the basis of structure. Autoimmun. Rev. 2006, 5, 367–372. [Google Scholar] [CrossRef] [PubMed]
- Yin, J.; Zheng, J.; Deng, F.; Zhao, W.; Chen, Y.; Huang, Q.; Huang, R.; Wen, L.; Yue, X.; Petersen, F.; et al. Gene Expression Profiling of Lacrimal Glands Identifies the Ectopic Expression of MHC II on Glandular Cells as a Presymptomatic Feature in a Mouse Model of Primary Sjogren’s Syndrome. Front. Immunol. 2018, 9, 2362. [Google Scholar] [CrossRef] [PubMed]
- Speight, P.M.; Cruchley, A.; Williams, D.M. Epithelial HLA-DR expression in labial salivary glands in Sjogren’s syndrome and non-specific sialadenitis. J. Oral Pathol. Med. 1989, 18, 178–183. [Google Scholar] [CrossRef] [PubMed]
- Fillatreau, S.; Manfroi, B.; Dorner, T. Toll-like receptor signalling in B cells during systemic lupus erythematosus. Nat. Rev. Rheumatol. 2021, 17, 98–108. [Google Scholar] [CrossRef]
- Avalos, A.M.; Uccellini, M.B.; Lenert, P.; Viglianti, G.A.; Marshak-Rothstein, A. FcgammaRIIB regulation of BCR/TLR-dependent autoreactive B-cell responses. Eur. J. Immunol. 2010, 40, 2692–2698. [Google Scholar] [CrossRef] [PubMed]
- Bolland, S.; Ravetch, J.V. Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis. Immunity 2000, 13, 277–285. [Google Scholar] [CrossRef]
- Barlev, A.N.; Malkiel, S.; Kurata-Sato, I.; Dorjee, A.L.; Suurmond, J.; Diamond, B. FcgammaRIIB regulates autoantibody responses by limiting marginal zone B cell activation. J. Clin. Investig. 2022, 132, e157250. [Google Scholar] [CrossRef]
- Corzo, C.A.; Varfolomeev, E.; Setiadi, A.F.; Francis, R.; Klabunde, S.; Senger, K.; Sujatha-Bhaskar, S.; Drobnick, J.; Do, S.; Suto, E.; et al. The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells. Sci. Signal. 2020, 13, eaaz1053. [Google Scholar] [CrossRef]
- Cosgrove, H.A.; Gingras, S.; Kim, M.; Bastacky, S.; Tilstra, J.S.; Shlomchik, M.J. B cell-intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice. JCI Insight 2023, 8, e172219. [Google Scholar] [CrossRef] [PubMed]
- Arbuckle, M.R.; McClain, M.T.; Rubertone, M.V.; Scofield, R.H.; Dennis, G.J.; James, J.A.; Harley, J.B. Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N. Engl. J. Med. 2003, 349, 1526–1533. [Google Scholar] [CrossRef]
- Derksen, V.; Huizinga, T.W.J.; van der Woude, D. The role of autoantibodies in the pathophysiology of rheumatoid arthritis. Semin. Immunopathol. 2017, 39, 437–446. [Google Scholar] [CrossRef]
- Lindop, R.; Arentz, G.; Thurgood, L.A.; Reed, J.H.; Jackson, M.W.; Gordon, T.P. Pathogenicity and proteomic signatures of autoantibodies to Ro and La. Immunol. Cell Biol. 2012, 90, 304–309. [Google Scholar] [CrossRef]
- Tonello, M.; Ruffatti, A.; Favaro, M.; Tison, T.; Del Ross, T.; Calligaro, A.; Hoxha, A.; Mattia, E.; Punzi, L. Maternal autoantibody profiles at risk for autoimmune congenital heart block: A prospective study in high-risk patients. Lupus Sci. Med. 2016, 3, e000129. [Google Scholar] [CrossRef]
- Miranda-Carus, M.E.; Askanase, A.D.; Clancy, R.M.; Di Donato, F.; Chou, T.M.; Libera, M.R.; Chan, E.K.; Buyon, J.P. Anti-SSA/Ro and anti-SSB/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages. J. Immunol. 2000, 165, 5345–5351. [Google Scholar] [CrossRef] [PubMed]
- Briassouli, P.; Komissarova, E.V.; Clancy, R.M.; Buyon, J.P. Role of the urokinase plasminogen activator receptor in mediating impaired efferocytosis of anti-SSA/Ro-bound apoptotic cardiocytes: Implications in the pathogenesis of congenital heart block. Circ. Res. 2010, 107, 374–387. [Google Scholar] [CrossRef] [PubMed]
- Robbins, A.; Hentzien, M.; Toquet, S.; Didier, K.; Servettaz, A.; Pham, B.N.; Giusti, D. Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52/TRIM21 Antibody Detection in Autoimmune Diseases. Front. Immunol. 2019, 10, 444. [Google Scholar] [CrossRef] [PubMed]
- Ching, K.H.; Burbelo, P.D.; Gonzalez-Begne, M.; Roberts, M.E.; Coca, A.; Sanz, I.; Iadarola, M.J. Salivary anti-Ro60 and anti-Ro52 antibody profiles to diagnose Sjogren’s Syndrome. J. Dent. Res. 2011, 90, 445–449. [Google Scholar] [CrossRef]
- Jonsson, R.; Theander, E.; Sjostrom, B.; Brokstad, K.; Henriksson, G. Autoantibodies present before symptom onset in primary Sjogren syndrome. JAMA 2013, 310, 1854–1855. [Google Scholar] [CrossRef]
- Theander, E.; Jonsson, R.; Sjostrom, B.; Brokstad, K.; Olsson, P.; Henriksson, G. Prediction of Sjogren’s Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling. Arthritis Rheumatol. 2015, 67, 2427–2436. [Google Scholar] [CrossRef]
- Lau, C.M.; Broughton, C.; Tabor, A.S.; Akira, S.; Flavell, R.A.; Mamula, M.J.; Christensen, S.R.; Shlomchik, M.J.; Viglianti, G.A.; Rifkin, I.R.; et al. RNA-associated autoantigens activate B cells by combined B cell antigen receptor/Toll-like receptor 7 engagement. J. Exp. Med. 2005, 202, 1171–1177. [Google Scholar] [CrossRef] [PubMed]
- Menendez, A.; Gomez, J.; Caminal-Montero, L.; Diaz-Lopez, J.B.; Cabezas-Rodriguez, I.; Mozo, L. Common and specific associations of anti-SSA/Ro60 and anti-Ro52/TRIM21 antibodies in systemic lupus erythematosus. Sci. World J. 2013, 2013, 832789. [Google Scholar] [CrossRef]
- Scofield, R.H. Autoantibodies as predictors of disease. Lancet 2004, 363, 1544–1546. [Google Scholar] [CrossRef] [PubMed]
- Lindop, R.; Arentz, G.; Bastian, I.; Whyte, A.F.; Thurgood, L.A.; Chataway, T.K.; Jackson, M.W.; Gordon, T.P. Long-term Ro60 humoral autoimmunity in primary Sjogren’s syndrome is maintained by rapid clonal turnover. Clin. Immunol. 2013, 148, 27–34. [Google Scholar] [CrossRef]
- Heinlen, L.D.; McClain, M.T.; Ritterhouse, L.L.; Bruner, B.F.; Edgerton, C.C.; Keith, M.P.; James, J.A.; Harley, J.B. 60 kD Ro and nRNP A frequently initiate human lupus autoimmunity. PLoS ONE 2010, 5, e9599. [Google Scholar] [CrossRef]
- Tetsuka, S.; Suzuki, T.; Ogawa, T.; Hashimoto, R.; Kato, H. Anti-Ro/SSA Antibodies May Be Responsible for Cerebellar Degeneration in Sjogren’s Syndrome. J. Clin. Med. Res. 2021, 13, 113–120. [Google Scholar] [CrossRef] [PubMed]
- Hu, C.; Huang, W.; Chen, H.; Song, G.; Li, P.; Shan, Q.; Zhang, X.; Zhang, F.; Zhu, H.; Wu, L.; et al. Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus. PLoS ONE 2015, 10, e0126643. [Google Scholar] [CrossRef]
- Lee, A.Y.S.; Beroukas, D.; Brown, L.; Lucchesi, C.; Kaur, A.; Gyedu, L.; Hughes, N.; Ng, Y.H.; Saran, O.; Gordon, T.P.; et al. Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles. Clin. Exp. Immunol. 2021, 203, 13–21. [Google Scholar] [CrossRef]
- Derksen, R.H.; Meilof, J.F. Anti-Ro/SS-A and anti-La/SS-B autoantibody levels in relation to systemic lupus erythematosus disease activity and congenital heart block. A longitudinal study comprising two consecutive pregnancies in a patient with systemic lupus erythematosus. Arthritis Rheum. 1992, 35, 953–959. [Google Scholar] [CrossRef]
- Fukuzumi, N.; Hayashi, N.; Saegusa, J.; Kinoshita, S.; Kawano, S.; Kumagai, S. Usefulness of anti-SS-A/Ro antibody measurement based on fluorescence enzyme immunoassay with Ro60 and Ro52 antigen. Rinsho Byori 2011, 59, 352–359. [Google Scholar] [PubMed]
- Chen, Y.L.; Hu, C.J.; Peng, L.Y.; Wang, C.H.; Zhao, Y.; Zhang, W.; Liu, D.Z.; Chinese Sjogren’s Syndrome Collaborative Research Group. Current state of technologies and recognition of anti-SSA/Ro antibodies in China: A multi-center study. J. Clin. Lab. Anal. 2021, 35, e24045. [Google Scholar] [CrossRef] [PubMed]
- Lee, A.Y.S.; Putty, T.; Lin, M.W.; Swaminathan, S.; Suan, D.; Chataway, T.; Thurlings, R.M.; Gordon, T.P.; Wang, J.J.; Reed, J.H. Isolated anti-Ro52 identifies a severe subset of Sjogren’s syndrome patients. Front. Immunol. 2023, 14, 1115548. [Google Scholar] [CrossRef] [PubMed]
- Zampeli, E.; Mavrommati, M.; Moutsopoulos, H.M.; Skopouli, F.N. Anti-Ro52 and/or anti-Ro60 immune reactivity: Autoantibody and disease associations. Clin. Exp. Rheumatol. 2020, 38 (Suppl. S126), 134–141. [Google Scholar] [PubMed]
- Chauhan, R.; Gupta, N.; Tiwari, A.K.; Raina, V.; Nandi, S.P. Development of a Novel Multiplex Bead-based Assay for Measuring Autoantibodies on Flow Cytometric Platform. Immunol. Investig. 2022, 51, 588–601. [Google Scholar] [CrossRef] [PubMed]
- Yuan, W.; Cao, H.; Li, W.; Wu, X.; Zheng, J. Comparison study of bead-based and line-blot multiplex ANA immunoassays in the diagnosis of systemic autoimmune rheumatic diseases. Clin. Rheumatol. 2022, 41, 899–909. [Google Scholar] [CrossRef] [PubMed]
- Satoh, M.; Tanaka, S.; Chan, E.K. The uses and misuses of multiplex autoantibody assays in systemic autoimmune rheumatic diseases. Front. Immunol. 2015, 6, 181. [Google Scholar] [CrossRef] [PubMed]
- Qin, Y.; Fan, C.; Wang, Y.; Feng, M.; Liang, Z.; Zhao, X.; Gao, C.; Luo, J. Analytical and clinical performance of different platforms simultaneously detecting 15 antinuclear antibodies. J. Clin. Lab. Anal. 2022, 36, e24554. [Google Scholar] [CrossRef]
- Deroo, L.; Achten, H.; De Boeck, K.; Genbrugge, E.; Bauters, W.; Roels, D.; Dochy, F.; Creytens, D.; Deprez, J.; Van den Bosch, F.; et al. The value of separate detection of anti-Ro52, anti-Ro60 and anti-SSB/La reactivities in relation to diagnosis and phenotypes in primary Sjogren’s syndrome. Clin. Exp. Rheumatol. 2022, 40, 2310–2317. [Google Scholar] [CrossRef]
- Hagiwara, S.; Tsuboi, H.; Honda, F.; Takahashi, H.; Kurata, I.; Ohyama, A.; Yagishita, M.; Abe, S.; Kurashima, Y.; Kaneko, S.; et al. Association of anti-Ro/SSA antibody with response to biologics in patients with rheumatoid arthritis. Mod. Rheumatol. 2016, 26, 857–862. [Google Scholar] [CrossRef]
- Chen, P.K.; Lan, J.L.; Chen, Y.M.; Chen, H.H.; Chang, S.H.; Chung, C.M.; Rutt, N.H.; Tan, T.M.; Mamat, R.N.R.; Anuar, N.D.; et al. Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA. J. Immunol. Res. 2021, 2021, 6656121. [Google Scholar] [CrossRef] [PubMed]
- Thursby, E.; Juge, N. Introduction to the human gut microbiota. Biochem. J. 2017, 474, 1823–1836. [Google Scholar] [CrossRef] [PubMed]
- Mousa, W.K.; Chehadeh, F.; Husband, S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol. 2022, 13, 906258. [Google Scholar] [CrossRef] [PubMed]
- Greiling, T.M.; Dehner, C.; Chen, X.; Hughes, K.; Iniguez, A.J.; Boccitto, M.; Ruiz, D.Z.; Renfroe, S.C.; Vieira, S.M.; Ruff, W.E.; et al. Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus. Sci. Transl. Med. 2018, 10, eaan2306. [Google Scholar] [CrossRef]
- Szymula, A.; Rosenthal, J.; Szczerba, B.M.; Bagavant, H.; Fu, S.M.; Deshmukh, U.S. T cell epitope mimicry between Sjogren’s syndrome Antigen A (SSA)/Ro60 and oral, gut, skin and vaginal bacteria. Clin. Immunol. 2014, 152, 1–9. [Google Scholar] [CrossRef]
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Mahla, R.S.; Jones, E.L.; Dustin, L.B. Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases. Int. J. Mol. Sci. 2024, 25, 7705. https://doi.org/10.3390/ijms25147705
Mahla RS, Jones EL, Dustin LB. Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases. International Journal of Molecular Sciences. 2024; 25(14):7705. https://doi.org/10.3390/ijms25147705
Chicago/Turabian StyleMahla, Ranjeet Singh, Esther L. Jones, and Lynn B. Dustin. 2024. "Ro60—Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases" International Journal of Molecular Sciences 25, no. 14: 7705. https://doi.org/10.3390/ijms25147705