{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:40:23Z","timestamp":1792010423281,"version":"4.4.0"},"reference-count":126,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,14]],"date-time":"2024-07-14T00:00:00Z","timestamp":1720915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Oxford\u2013Bristol Myers Squibb\u2013Celgene Research Fellowship Programme","award":["Q323RSV101"],"award-info":[{"award-number":["Q323RSV101"]}]},{"DOI":"10.13039\/501100008741","name":"EULAR","doi-asserted-by":"publisher","award":["Q323RSV101"],"award-info":[{"award-number":["Q323RSV101"]}],"id":[{"id":"10.13039\/501100008741","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Kennedy Trust for Rheumatology Research","award":["Q323RSV101"],"award-info":[{"award-number":["Q323RSV101"]}]},{"name":"Henni Mester Fellowship (University College, University of Oxford)","award":["Q323RSV101"],"award-info":[{"award-number":["Q323RSV101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Ro60\/SSA2 autoantigen is an RNA-binding protein and a core component of nucleocytoplasmic ribonucleoprotein (RNP) complexes. Ro60 is essential in RNA metabolism, cell stress response pathways, and cellular homeostasis. It stabilises and mediates the quality control and cellular distribution of small RNAs, including YRNAs (for the \u2018y\u2019 in \u2018cytoplasmic\u2019), retroelement transcripts, and misfolded RNAs. Ro60 transcriptional dysregulation or loss of function can result in the generation and release of RNA fragments from YRNAs and other small RNAs. Small RNA fragments can instigate an inflammatory cascade through endosomal toll-like receptors (TLRs) and cytoplasmic RNA sensors, which typically sense pathogen-associated molecular patterns, and mount the first line of defence against invading pathogens. However, the recognition of host-originating RNA moieties from Ro60 RNP complexes can activate inflammatory response pathways and compromise self-tolerance. Autoreactive B cells may produce antibodies targeting extracellular Ro60 RNP complexes. Ro60 autoantibodies serve as diagnostic markers for various autoimmune diseases, including Sj\u00f6gren\u2019s disease (SjD) and systemic lupus erythematosus (SLE), and they may also act as predictive markers for anti-drug antibody responses among rheumatic patients. Understanding Ro60\u2019s structure, function, and role in self-tolerance can enhance our understanding of the underlying molecular mechanisms of autoimmune conditions.<\/jats:p>","DOI":"10.3390\/ijms25147705","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T15:17:06Z","timestamp":1721056626000},"page":"7705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Ro60\u2014Roles in RNA Processing, Inflammation, and Rheumatic Autoimmune Diseases"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5525-8442","authenticated-orcid":false,"given":"Ranjeet Singh","family":"Mahla","sequence":"first","affiliation":[{"name":"The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1032-650X","authenticated-orcid":false,"given":"Esther L.","family":"Jones","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-1867","authenticated-orcid":false,"given":"Lynn B.","family":"Dustin","sequence":"additional","affiliation":[{"name":"The Kennedy Institute of Rheumatology, University of Oxford, Oxford OX3 7FY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,14]]},"reference":[{"key":"ref_1","first-page":"389","article-title":"Ro60 Expression Decreases with Age in Peripheral Blood Mononuclear Cells of Children and Adolescents and Correlates with Tlr7 Stimulation in Pdcs of Prepubertal Children","volume":"76","author":"Radziszewska","year":"2017","journal-title":"Ann. Rheum. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2148","DOI":"10.4049\/jimmunol.0902248","article-title":"Ro60-associated single-stranded RNA links inflammation with fetal cardiac fibrosis via ligation of TLRs: A novel pathway to autoimmune-associated heart block","volume":"184","author":"Clancy","year":"2010","journal-title":"J. Immunol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1126\/science.aac7442","article-title":"The Ro60 autoantigen binds endogenous retroelements and regulates inflammatory gene expression","volume":"350","author":"Hung","year":"2015","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2891","DOI":"10.1101\/gad.8.23.2891","article-title":"A possible role for the 60-kD Ro autoantigen in a discard pathway for defective 5S rRNA precursors","volume":"8","author":"Wolin","year":"1994","journal-title":"Genes Dev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3109\/08916939908994052","article-title":"The 5S rRNA is associated with Ro60 ribonucleoprotein and is co-precipitated with hYRNAs by anti-Ro antibodies","volume":"31","author":"Moreno","year":"1999","journal-title":"Autoimmunity"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1038\/nrg2111","article-title":"RNA regulons: Coordination of post-transcriptional events","volume":"8","author":"Keene","year":"2007","journal-title":"Nat. Rev. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1977","DOI":"10.1016\/j.febslet.2008.03.004","article-title":"RNA-binding proteins and post-transcriptional gene regulation","volume":"582","author":"Glisovic","year":"2008","journal-title":"FEBS Lett."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41584-023-00980-y","article-title":"Post-transcriptional checkpoints in autoimmunity","volume":"19","author":"Bechara","year":"2023","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1038\/s41580-023-00628-5","article-title":"Cellular functions of eukaryotic RNA helicases and their links to human diseases","volume":"24","author":"Bohnsack","year":"2023","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1038\/s41580-023-00694-9","article-title":"Transcription regulation by long non-coding RNAs: Mechanisms and disease relevance","volume":"25","author":"Ferrer","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1038\/s41576-023-00662-1","article-title":"Non-coding RNAs in disease: From mechanisms to therapeutics","volume":"25","author":"Nemeth","year":"2024","journal-title":"Nat. Rev. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1172\/JCI114551","article-title":"Human Ro ribonucleoprotein particles: Characterization of native structure and stable association with the La polypeptide","volume":"85","author":"Boire","year":"1990","journal-title":"J. Clin. Investig."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/978-981-15-1671-9_20","article-title":"Y RNAs: Biogenesis, Function and Implications for the Cardiovascular System","volume":"1229","author":"Valkov","year":"2020","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Langley, A.R., Chambers, H., Christov, C.P., and Krude, T. (2010). Ribonucleoprotein particles containing non-coding Y RNAs, Ro60, La and nucleolin are not required for Y RNA function in DNA replication. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0013673"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"14960","DOI":"10.1074\/jbc.M611163200","article-title":"Crystal structure of Rsr, an ortholog of the antigenic Ro protein, links conformational flexibility to RNA binding activity","volume":"282","author":"Ramesh","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1038\/nsmb1156","article-title":"Structural and biochemical basis for misfolded RNA recognition by the Ro autoantigen","volume":"13","author":"Fuchs","year":"2006","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.cell.2005.03.009","article-title":"Structural insights into RNA quality control: The Ro autoantigen binds misfolded RNAs via its central cavity","volume":"121","author":"Stein","year":"2005","journal-title":"Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/S0934-8832(11)80025-9","article-title":"Type A modules: Interacting domains found in several non-fibrillar collagens and in other extracellular matrix proteins","volume":"13","author":"Colombatti","year":"1993","journal-title":"Matrix"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3369","DOI":"10.1091\/mbc.e02-05-0259","article-title":"Distribution and evolution of von Willebrand\/integrin A domains: Widely dispersed domains with roles in cell adhesion and elsewhere","volume":"13","author":"Whittaker","year":"2002","journal-title":"Mol. Biol. Cell"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bateman, A., and Kickhoefer, V. (2003). The TROVE module: A common element in Telomerase, Ro and Vault ribonucleoproteins. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-49"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1017\/S1355838201002503","article-title":"Identification of a novel cis-acting RNA element involved in nuclear export of hY RNAs","volume":"7","author":"Rutjes","year":"2001","journal-title":"RNA"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.biocel.2015.07.003","article-title":"Functional roles of non-coding Y RNAs","volume":"66","author":"Kowalski","year":"2015","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"5848","DOI":"10.1021\/bi500470b","article-title":"Nucleotide contributions to the structural integrity and DNA replication initiation activity of noncoding y RNA","volume":"53","author":"Wang","year":"2014","journal-title":"Biochemistry"},{"key":"ref_24","first-page":"1134","article-title":"La antigen recognizes and binds to the 3\u2019-oligouridylate tail of a small RNA","volume":"4","author":"Mathews","year":"1984","journal-title":"Mol. Cell. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1017\/S1355838298971667","article-title":"Binding of the 60-kDa Ro autoantigen to Y RNAs: Evidence for recognition in the major groove of a conserved helix","volume":"4","author":"Green","year":"1998","journal-title":"RNA"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1996","DOI":"10.1073\/pnas.81.7.1996","article-title":"The Ro small cytoplasmic ribonucleoproteins: Identification of the antigenic protein and its binding site on the Ro RNAs","volume":"81","author":"Wolin","year":"1984","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5173","DOI":"10.1093\/nar\/19.19.5173","article-title":"Analysis of protein\u2014RNA interactions within Ro ribonucleoprotein complexes","volume":"19","author":"Pruijn","year":"1991","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Spurlock, C.F., Tossberg, J.T., Guo, Y., Sriram, S., Crooke, P.S., and Aune, T.M. (2015). Defective structural RNA processing in relapsing-remitting multiple sclerosis. Genome Biol., 16.","DOI":"10.1186\/s13059-015-0629-x"},{"key":"ref_29","first-page":"769","article-title":"A misfolded form of 5S rRNA is complexed with the Ro and La autoantigens","volume":"2","author":"Shi","year":"1996","journal-title":"RNA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"3067","DOI":"10.1101\/gad.1603907","article-title":"Human Y5 RNA specializes a Ro ribonucleoprotein for 5S ribosomal RNA quality control","volume":"21","author":"Hogg","year":"2007","journal-title":"Genes Dev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"D180","DOI":"10.1093\/nar\/gkv1081","article-title":"5SRNAdb: An information resource for 5S ribosomal RNAs","volume":"44","author":"Szymanski","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Deininger, P. (2011). Alu elements: Know the SINEs. Genome Biol., 12.","DOI":"10.1186\/gb-2011-12-12-236"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1002\/wsbm.10","article-title":"Adenosine-to-inosine RNA editing","volume":"1","author":"Zinshteyn","year":"2009","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Savva, Y.A., Rieder, L.E., and Reenan, R.A. (2012). The ADAR protein family. Genome Biol., 13.","DOI":"10.1186\/gb-2012-13-12-252"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"102755","DOI":"10.1016\/j.jaut.2021.102755","article-title":"Adenosine-to-inosine RNA editing contributes to type I interferon responses in systemic sclerosis","volume":"125","author":"Vlachogiannis","year":"2021","journal-title":"J. Autoimmun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1038\/s41586-022-05052-x","article-title":"RNA editing underlies genetic risk of common inflammatory diseases","volume":"608","author":"Li","year":"2022","journal-title":"Nature"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1093\/nar\/gks1353","article-title":"RNA-interacting proteins act as site-specific repressors of ADAR2-mediated RNA editing and fluctuate upon neuronal stimulation","volume":"41","author":"Tariq","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"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., and Pratt, G.A. (2019). Regulation of RNA editing by RNA-binding proteins in human cells. Commun. Biol., 2.","DOI":"10.1038\/s42003-018-0271-8"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102329","DOI":"10.1016\/j.jaut.2019.102329","article-title":"Increased adenosine-to-inosine RNA editing in rheumatoid arthritis","volume":"106","author":"Vlachogiannis","year":"2020","journal-title":"J. Autoimmun."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1515\/hsz-2013-0165","article-title":"Structural features of antiviral DNA cytidine deaminases","volume":"394","author":"Vasudevan","year":"2013","journal-title":"Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2165","DOI":"10.1128\/JVI.02287-06","article-title":"Antiviral protein APOBEC3G localizes to ribonucleoprotein complexes found in P bodies and stress granules","volume":"81","author":"Kramer","year":"2007","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"108649","DOI":"10.1016\/j.clim.2020.108649","article-title":"Expression of APOBEC family members as regulators of endogenous retroelements and malignant transformation in systemic autoimmunity","volume":"223","author":"Mavragani","year":"2021","journal-title":"Clin. Immunol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1016\/j.rdc.2016.03.002","article-title":"Autoantibodies in Sjogren\u2019s Syndrome","volume":"42","author":"Fayyaz","year":"2016","journal-title":"Rheum. Dis. Clin. N. Am."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Jones, E.L., Laidlaw, S.M., and Dustin, L.B. (2021). TRIM21\/Ro52\u2014Roles in Innate Immunity and Autoimmune Disease. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.738473"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4049\/jimmunol.102.1.117","article-title":"Characterization of a Soluble Cytoplasmic Antigen Reactive with Sera from Patients with Systemic Lupus Erythmatosus","volume":"102","author":"Clark","year":"1969","journal-title":"J. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4709","DOI":"10.1007\/s00216-018-1407-x","article-title":"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","volume":"411","author":"Monzo","year":"2019","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.molimm.2004.03.036","article-title":"Interaction of calcium and Ro60: Increase of antigenicity","volume":"41","author":"Scofield","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1007\/978-1-4939-2718-0_26","article-title":"On-Membrane Renaturation of Recombinant Ro60 Autoantigen by Calcium Ions","volume":"1314","author":"Kurien","year":"2015","journal-title":"Methods Mol. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1016\/j.freeradbiomed.2010.10.687","article-title":"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","volume":"50","author":"Kurien","year":"2011","journal-title":"Free Radic. Biol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"110","DOI":"10.4049\/jimmunol.1202849","article-title":"Ro60 Requires Y3 RNA for Cell Surface Exposure and Inflammation Associated with Cardiac Manifestations of Neonatal Lupus","volume":"191","author":"Reed","year":"2013","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Gao, Y., Qin, Y., Wan, C., Sun, Y., Meng, J., Huang, J., Hu, Y., Jin, H., and Yang, K. (2021). Small Extracellular Vesicles: A Novel Avenue for Cancer Management. Front. Oncol., 11.","DOI":"10.3389\/fonc.2021.638357"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1517","DOI":"10.1002\/art.21005","article-title":"Salivary gland epithelial cell exosomes: A source of autoantigenic ribonucleoproteins","volume":"52","author":"Kapsogeorgou","year":"2005","journal-title":"Arthritis Rheumatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1764213","DOI":"10.1080\/20013078.2020.1764213","article-title":"Y-RNA subtype ratios in plasma extracellular vesicles are cell type- specific and are candidate biomarkers for inflammatory diseases","volume":"9","author":"Driedonks","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Driedonks, T.A.P., and Nolte-\u2019t Hoen, E.N.M. (2018). Circulating Y-RNAs in Extracellular Vesicles and Ribonucleoprotein Complexes; Implications for the Immune System. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.03164"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"337","DOI":"10.15252\/emmm.201606924","article-title":"Y RNA fragment in extracellular vesicles confers cardioprotection via modulation of IL-10 expression and secretion","volume":"9","author":"Cambier","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.1261\/rna.053629.115","article-title":"Extracellular vesicle-mediated transfer of processed and functional RNY5 RNA","volume":"21","author":"Chakrabortty","year":"2015","journal-title":"RNA"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1046\/j.1365-3083.2002.01072_79.x","article-title":"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\u2019s syndrome","volume":"56","author":"Ohlsson","year":"2002","journal-title":"Scand. J. Immunol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1557","DOI":"10.1084\/jem.181.4.1557","article-title":"Novel packages of viral and self-antigens are generated during apoptosis","volume":"181","author":"Rosen","year":"1995","journal-title":"J. Exp. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1111\/j.1365-2249.2005.03001.x","article-title":"Neo-epitopes are required for immunogenicity of the La\/SS-B nuclear antigen in the context of late apoptotic cells","volume":"143","author":"Pan","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1002\/art.23377","article-title":"A B cell apotope of Ro 60 in systemic lupus erythematosus","volume":"58","author":"Reed","year":"2008","journal-title":"Arthritis Rheum."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/S0003-9969(02)00025-0","article-title":"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","volume":"47","author":"McArthur","year":"2002","journal-title":"Arch. Oral Biol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e2530","DOI":"10.1038\/cddis.2016.429","article-title":"RNY (YRNA)-derived small RNAs regulate cell death and inflammation in monocytes\/macrophages","volume":"8","author":"Hizir","year":"2017","journal-title":"Cell Death Dis."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3582","DOI":"10.1002\/eji.200737815","article-title":"Treatment of lupus-prone mice with a dual inhibitor of TLR7 and TLR9 leads to reduction of autoantibody production and amelioration of disease symptoms","volume":"37","author":"Barrat","year":"2007","journal-title":"Eur. J. Immunol."},{"key":"ref_64","first-page":"301274","article-title":"Neonatal lupus erythematosus","volume":"2012","author":"Hon","year":"2012","journal-title":"Autoimmune Dis."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Buyon, J.P., Saxena, A., Izmirly, P.M., Cuneo, B., and Wainwright, B. (2021). Neonatal lupus: Clinical spectrum, biomarkers, pathogenesis, and approach to treatment. Systemic Lupus Erythematosus, Elsevier. [2nd ed.].","DOI":"10.1016\/B978-0-12-814551-7.00053-2"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Murakami, Y., Fukui, R., Tanaka, R., Motoi, Y., Kanno, A., Sato, R., Yamaguchi, K., Amano, H., Furukawa, Y., and Suzuki, H. (2021). Anti-TLR7 Antibody Protects Against Lupus Nephritis in NZBWF1 Mice by Targeting B Cells and Patrolling Monocytes. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.777197"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"39789","DOI":"10.1074\/jbc.M112.383000","article-title":"Activation of autoreactive B cells by endogenous TLR7 and TLR3 RNA ligands","volume":"287","author":"Green","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"677","DOI":"10.1038\/nm.3893","article-title":"Inflammasomes: Mechanism of action, role in disease, and therapeutics","volume":"21","author":"Guo","year":"2015","journal-title":"Nat. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"102299","DOI":"10.1016\/j.jaut.2019.06.010","article-title":"Inflammasomes and autoimmune and rheumatic diseases: A comprehensive review","volume":"103","author":"Shin","year":"2019","journal-title":"J. Autoimmun."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Chen, B., Wang, Y., and Chen, G. (2023). New Potentiality of Bioactive Substances: Regulating the NLRP3 Inflammasome in Autoimmune Diseases. Nutrients, 15.","DOI":"10.3390\/nu15214584"},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Demarco, B., Danielli, S., Fischer, F.A., and Bezbradica, J.S. (2022). How Pyroptosis Contributes to Inflammation and Fibroblast-Macrophage Cross-Talk in Rheumatoid Arthritis. Cells, 11.","DOI":"10.3390\/cells11081307"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.molmed.2010.11.001","article-title":"Inflammasomes and autoimmunity","volume":"17","author":"Shaw","year":"2011","journal-title":"Trends Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.cca.2017.09.019","article-title":"Enhanced expression of NLRP3 inflammasome-related inflammation in peripheral blood mononuclear cells in Sjogren\u2019s syndrome","volume":"474","author":"Kim","year":"2017","journal-title":"Clin. Chim. Acta"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.jaut.2018.02.010","article-title":"Systemic activation of NLRP3 inflammasome in patients with severe primary Sjogren\u2019s syndrome fueled by inflammagenic DNA accumulations","volume":"91","author":"Vakrakou","year":"2018","journal-title":"J. Autoimmun."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/s41584-021-00605-2","article-title":"Epithelial-immune cell interplay in primary Sjogren syndrome salivary gland pathogenesis","volume":"17","author":"Verstappen","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Zhao, C., and Zhao, W. (2020). NLRP3 Inflammasome-A Key Player in Antiviral Responses. Front. Immunol., 11.","DOI":"10.3389\/fimmu.2020.00211"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/bs.ai.2016.07.001","article-title":"Endogenous Retroelements and the Host Innate Immune Sensors","volume":"132","author":"Mu","year":"2016","journal-title":"Adv. Immunol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/j.cell.2012.03.036","article-title":"DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88","volume":"149","author":"Tarallo","year":"2012","journal-title":"Cell"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"5732","DOI":"10.4049\/jimmunol.1501606","article-title":"DDX19A Senses Viral RNA and Mediates NLRP3-Dependent Inflammasome Activation","volume":"195","author":"Li","year":"2015","journal-title":"J. Immunol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.immuni.2013.07.001","article-title":"The DHX33 RNA helicase senses cytosolic RNA and activates the NLRP3 inflammasome","volume":"39","author":"Mitoma","year":"2013","journal-title":"Immunity"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e158791","DOI":"10.1172\/jci.insight.158791","article-title":"Alu RNA induces NLRP3 expression through TLR7 activation in alpha-1-antitrypsin-deficient macrophages","volume":"7","author":"Lee","year":"2022","journal-title":"JCI Insight"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1046\/j.1365-2362.1996.186316.x","article-title":"Epitope mapping of the Ro\/SSA60KD autoantigen reveals disease-specific antibody-binding profiles","volume":"26","author":"Routsias","year":"1996","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1038\/nm1167","article-title":"Early events in lupus humoral autoimmunity suggest initiation through molecular mimicry","volume":"11","author":"McClain","year":"2005","journal-title":"Nat. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1016\/j.autrev.2005.10.004","article-title":"The Ro 60 kDa autoantigen comes into focus: Interpreting epitope mapping experiments on the basis of structure","volume":"5","author":"Wolin","year":"2006","journal-title":"Autoimmun. Rev."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Yin, J., Zheng, J., Deng, F., Zhao, W., Chen, Y., Huang, Q., Huang, R., Wen, L., Yue, X., and Petersen, F. (2018). 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\u2019s Syndrome. Front. Immunol., 9.","DOI":"10.3389\/fimmu.2018.02362"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1111\/j.1600-0714.1989.tb00758.x","article-title":"Epithelial HLA-DR expression in labial salivary glands in Sjogren\u2019s syndrome and non-specific sialadenitis","volume":"18","author":"Speight","year":"1989","journal-title":"J. Oral Pathol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1038\/s41584-020-00544-4","article-title":"Toll-like receptor signalling in B cells during systemic lupus erythematosus","volume":"17","author":"Fillatreau","year":"2021","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1002\/eji.200940184","article-title":"FcgammaRIIB regulation of BCR\/TLR-dependent autoreactive B-cell responses","volume":"40","author":"Avalos","year":"2010","journal-title":"Eur. J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S1074-7613(00)00027-3","article-title":"Spontaneous autoimmune disease in Fc(gamma)RIIB-deficient mice results from strain-specific epistasis","volume":"13","author":"Bolland","year":"2000","journal-title":"Immunity"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"e157250","DOI":"10.1172\/JCI157250","article-title":"FcgammaRIIB regulates autoantibody responses by limiting marginal zone B cell activation","volume":"132","author":"Barlev","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"eaaz1053","DOI":"10.1126\/scisignal.aaz1053","article-title":"The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells","volume":"13","author":"Corzo","year":"2020","journal-title":"Sci. Signal."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e172219","DOI":"10.1172\/jci.insight.172219","article-title":"B cell-intrinsic TLR7 expression drives severe lupus in TLR9-deficient mice","volume":"8","author":"Cosgrove","year":"2023","journal-title":"JCI Insight"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1526","DOI":"10.1056\/NEJMoa021933","article-title":"Development of autoantibodies before the clinical onset of systemic lupus erythematosus","volume":"349","author":"Arbuckle","year":"2003","journal-title":"N. Engl. J. Med."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00281-017-0627-z","article-title":"The role of autoantibodies in the pathophysiology of rheumatoid arthritis","volume":"39","author":"Derksen","year":"2017","journal-title":"Semin. Immunopathol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1038\/icb.2011.108","article-title":"Pathogenicity and proteomic signatures of autoantibodies to Ro and La","volume":"90","author":"Lindop","year":"2012","journal-title":"Immunol. Cell Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e000129","DOI":"10.1136\/lupus-2015-000129","article-title":"Maternal autoantibody profiles at risk for autoimmune congenital heart block: A prospective study in high-risk patients","volume":"3","author":"Tonello","year":"2016","journal-title":"Lupus Sci. Med."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5345","DOI":"10.4049\/jimmunol.165.9.5345","article-title":"Anti-SSA\/Ro and anti-SSB\/La autoantibodies bind the surface of apoptotic fetal cardiocytes and promote secretion of TNF-alpha by macrophages","volume":"165","author":"Askanase","year":"2000","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1161\/CIRCRESAHA.109.213629","article-title":"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","volume":"107","author":"Briassouli","year":"2010","journal-title":"Circ. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Robbins, A., Hentzien, M., Toquet, S., Didier, K., Servettaz, A., Pham, B.N., and Giusti, D. (2019). Diagnostic Utility of Separate Anti-Ro60 and Anti-Ro52\/TRIM21 Antibody Detection in Autoimmune Diseases. Front. Immunol., 10.","DOI":"10.3389\/fimmu.2019.00444"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1177\/0022034510390811","article-title":"Salivary anti-Ro60 and anti-Ro52 antibody profiles to diagnose Sjogren\u2019s Syndrome","volume":"90","author":"Ching","year":"2011","journal-title":"J. Dent. Res."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1854","DOI":"10.1001\/jama.2013.278448","article-title":"Autoantibodies present before symptom onset in primary Sjogren syndrome","volume":"310","author":"Jonsson","year":"2013","journal-title":"JAMA"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"2427","DOI":"10.1002\/art.39214","article-title":"Prediction of Sjogren\u2019s Syndrome Years Before Diagnosis and Identification of Patients With Early Onset and Severe Disease Course by Autoantibody Profiling","volume":"67","author":"Theander","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1084\/jem.20050630","article-title":"RNA-associated autoantigens activate B cells by combined B cell antigen receptor\/Toll-like receptor 7 engagement","volume":"202","author":"Lau","year":"2005","journal-title":"J. Exp. Med."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"832789","DOI":"10.1155\/2013\/832789","article-title":"Common and specific associations of anti-SSA\/Ro60 and anti-Ro52\/TRIM21 antibodies in systemic lupus erythematosus","volume":"2013","author":"Menendez","year":"2013","journal-title":"Sci. World J."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.1016\/S0140-6736(04)16154-0","article-title":"Autoantibodies as predictors of disease","volume":"363","author":"Scofield","year":"2004","journal-title":"Lancet"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.clim.2013.03.015","article-title":"Long-term Ro60 humoral autoimmunity in primary Sjogren\u2019s syndrome is maintained by rapid clonal turnover","volume":"148","author":"Lindop","year":"2013","journal-title":"Clin. Immunol."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Heinlen, L.D., McClain, M.T., Ritterhouse, L.L., Bruner, B.F., Edgerton, C.C., Keith, M.P., James, J.A., and Harley, J.B. (2010). 60 kD Ro and nRNP A frequently initiate human lupus autoimmunity. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0009599"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"113","DOI":"10.14740\/jocmr4429","article-title":"Anti-Ro\/SSA Antibodies May Be Responsible for Cerebellar Degeneration in Sjogren\u2019s Syndrome","volume":"13","author":"Tetsuka","year":"2021","journal-title":"J. Clin. Med. Res."},{"key":"ref_109","doi-asserted-by":"crossref","unstructured":"Hu, C., Huang, W., Chen, H., Song, G., Li, P., Shan, Q., Zhang, X., Zhang, F., Zhu, H., and Wu, L. (2015). Autoantibody profiling on human proteome microarray for biomarker discovery in cerebrospinal fluid and sera of neuropsychiatric lupus. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0126643"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1111\/cei.13508","article-title":"Identification of a unique anti-Ro60 subset with restricted serological and molecular profiles","volume":"203","author":"Lee","year":"2021","journal-title":"Clin. Exp. Immunol."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1002\/art.1780350817","article-title":"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","volume":"35","author":"Derksen","year":"1992","journal-title":"Arthritis Rheum."},{"key":"ref_112","first-page":"352","article-title":"Usefulness of anti-SS-A\/Ro antibody measurement based on fluorescence enzyme immunoassay with Ro60 and Ro52 antigen","volume":"59","author":"Fukuzumi","year":"2011","journal-title":"Rinsho Byori"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"e24045","DOI":"10.1002\/jcla.24045","article-title":"Current state of technologies and recognition of anti-SSA\/Ro antibodies in China: A multi-center study","volume":"35","author":"Chen","year":"2021","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Lee, A.Y.S., Putty, T., Lin, M.W., Swaminathan, S., Suan, D., Chataway, T., Thurlings, R.M., Gordon, T.P., Wang, J.J., and Reed, J.H. (2023). Isolated anti-Ro52 identifies a severe subset of Sjogren\u2019s syndrome patients. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1115548"},{"key":"ref_115","first-page":"134","article-title":"Anti-Ro52 and\/or anti-Ro60 immune reactivity: Autoantibody and disease associations","volume":"38","author":"Zampeli","year":"2020","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1080\/08820139.2020.1854782","article-title":"Development of a Novel Multiplex Bead-based Assay for Measuring Autoantibodies on Flow Cytometric Platform","volume":"51","author":"Chauhan","year":"2022","journal-title":"Immunol. Investig."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1007\/s10067-021-05946-7","article-title":"Comparison study of bead-based and line-blot multiplex ANA immunoassays in the diagnosis of systemic autoimmune rheumatic diseases","volume":"41","author":"Yuan","year":"2022","journal-title":"Clin. Rheumatol."},{"key":"ref_118","doi-asserted-by":"crossref","unstructured":"Satoh, M., Tanaka, S., and Chan, E.K. (2015). The uses and misuses of multiplex autoantibody assays in systemic autoimmune rheumatic diseases. Front. Immunol., 6.","DOI":"10.3389\/fimmu.2015.00181"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"e24554","DOI":"10.1002\/jcla.24554","article-title":"Analytical and clinical performance of different platforms simultaneously detecting 15 antinuclear antibodies","volume":"36","author":"Qin","year":"2022","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_120","first-page":"2310","article-title":"The value of separate detection of anti-Ro52, anti-Ro60 and anti-SSB\/La reactivities in relation to diagnosis and phenotypes in primary Sjogren\u2019s syndrome","volume":"40","author":"Deroo","year":"2022","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"857","DOI":"10.3109\/14397595.2016.1153567","article-title":"Association of anti-Ro\/SSA antibody with response to biologics in patients with rheumatoid arthritis","volume":"26","author":"Hagiwara","year":"2016","journal-title":"Mod. Rheumatol."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"6656121","DOI":"10.1155\/2021\/6656121","article-title":"Anti-TROVE2 Antibody Determined by Immune-Related Array May Serve as a Predictive Marker for Adalimumab Immunogenicity and Effectiveness in RA","volume":"2021","author":"Chen","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"1823","DOI":"10.1042\/BCJ20160510","article-title":"Introduction to the human gut microbiota","volume":"474","author":"Thursby","year":"2017","journal-title":"Biochem. J."},{"key":"ref_124","doi-asserted-by":"crossref","unstructured":"Mousa, W.K., Chehadeh, F., and Husband, S. (2022). Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.906258"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"eaan2306","DOI":"10.1126\/scitranslmed.aan2306","article-title":"Commensal orthologs of the human autoantigen Ro60 as triggers of autoimmunity in lupus","volume":"10","author":"Greiling","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2014.02.004","article-title":"T cell epitope mimicry between Sjogren\u2019s syndrome Antigen A (SSA)\/Ro60 and oral, gut, skin and vaginal bacteria","volume":"152","author":"Szymula","year":"2014","journal-title":"Clin. Immunol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/14\/7705\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T15:16:34Z","timestamp":1760109394000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/14\/7705"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,14]]},"references-count":126,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2024,7]]}},"alternative-id":["ijms25147705"],"URL":"https:\/\/doi.org\/10.3390\/ijms25147705","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,14]]}}}