Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation
© 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology..
OBJECTIVE: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status.
METHODS: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients.
RESULTS: In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher β2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations.
CONCLUSION: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:76 |
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Enthalten in: |
Arthritis & rheumatology (Hoboken, N.J.) - 76(2024), 5 vom: 01. Apr., Seite 751-762 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Bettacchioli, Eléonore [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 25.04.2024 Date Revised 25.04.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1002/art.42789 |
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funding: |
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PPN (Katalog-ID): |
NLM36620677X |
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245 | 1 | 0 | |a Association of Combined Anti-Ro52/TRIM21 and Anti-Ro60/SSA Antibodies With Increased Sjögren Disease Severity Through Interferon Pathway Activation |
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500 | |a Citation Status MEDLINE | ||
520 | |a © 2023 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology. | ||
520 | |a OBJECTIVE: The biologic diagnosis of primary Sjögren disease (SjD) mainly relies on anti-Ro60/SSA antibodies, whereas the significance of anti-Ro52/TRIM21 antibodies currently remains unclear. The aim of this study was to characterize the clinical, serological, biologic, transcriptomic, and interferon profiles of patients with SjD according to their anti-Ro52/TRIM21 antibody status | ||
520 | |a METHODS: Patients with SjD from the European PRECISESADS (n = 376) and the Brittany Diagnostic Suspicion of primitive Sjögren's Syndrome (DIApSS); (n = 146) cohorts were divided into four groups: double negative (Ro52-/Ro60-), isolated anti-Ro52/TRIM21 positive (Ro52+), isolated anti-Ro60/SSA positive (Ro60+), and double-positive (Ro52+/Ro60+) patients. Clinical information; EULAR Sjögren Syndrome Disease Activity Index, a score representing systemic activity; and biologic markers associated with disease severity were evaluated. Transcriptome data obtained from whole blood by RNA sequencing and type I and II interferon signatures were analyzed for PRECISESADS patients | ||
520 | |a RESULTS: In the DIApSS cohort, Ro52+/Ro60+ patients showed significantly more parotidomegaly (33.3% vs 0%-11%) along with higher β2-microglobulin (P = 0.0002), total immunoglobulin (P < 0.0001), and erythrocyte sedimentation rate levels (P = 0.002) as well as rheumatoid factor (RF) positivity (66.2% vs 20.8%-25%) compared to other groups. The PRECISESADS cohort corroborated these observations, with increased arthritis (P = 0.046), inflammation (P = 0.005), hypergammaglobulinemia (P < 0.0001), positive RF (P < 0.0001), leukopenia (P = 0.004), and lymphopenia (P = 0.009) in Ro52+/Ro60+ patients. Cumulative EULAR Sjögren Syndrome Disease Activity Index results further confirmed these disparities (P = 0.002). Transcriptome analysis linked anti-Ro52/TRIM21 antibody positivity to interferon pathway activation as an underlying cause for these clinical correlations | ||
520 | |a CONCLUSION: These results suggest that the combination of anti-Ro52/TRIM21 and anti-Ro60/SSA antibodies is associated with a clinical, biologic, and transcriptional profile linked to greater disease severity in SjD through the potentiation of the interferon pathway activation by anti-Ro52/TRIM21 antibodies | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 7 | |a SS-A antigen |2 NLM | |
650 | 7 | |a Ribonucleoproteins |2 NLM | |
650 | 7 | |a RO60 protein, human |2 NLM | |
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650 | 7 | |a Interferons |2 NLM | |
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650 | 7 | |a RNA, Small Cytoplasmic |2 NLM | |
700 | 1 | |a Saraux, Alain |e verfasserin |4 aut | |
700 | 1 | |a Tison, Alice |e verfasserin |4 aut | |
700 | 1 | |a Cornec, Divi |e verfasserin |4 aut | |
700 | 1 | |a Dueymes, Maryvonne |e verfasserin |4 aut | |
700 | 1 | |a Foulquier, Nathan |e verfasserin |4 aut | |
700 | 1 | |a Hillion, Sophie |e verfasserin |4 aut | |
700 | 1 | |a Roguedas-Contios, Anne-Marie |e verfasserin |4 aut | |
700 | 1 | |a Benyoussef, Anas-Alexis |e verfasserin |4 aut | |
700 | 1 | |a Alarcon-Riquelme, Marta E |e verfasserin |4 aut | |
700 | 1 | |a Pers, Jacques-Olivier |e verfasserin |4 aut | |
700 | 1 | |a Devauchelle-Pensec, Valérie |e verfasserin |4 aut | |
700 | 0 | |a PRECISESADS Clinical Consortium, and PRECISESADS Sjögren Consortium |e verfasserin |4 aut | |
700 | 1 | |a Beretta, Lorenzo |e investigator |4 oth | |
700 | 1 | |a Vigone, Barbara |e investigator |4 oth | |
700 | 1 | |a Pers, Jacques-Olivier |e investigator |4 oth | |
700 | 1 | |a Saraux, Alain |e investigator |4 oth | |
700 | 1 | |a Devauchelle-Pensec, Valérie |e investigator |4 oth | |
700 | 1 | |a Cornec, Divi |e investigator |4 oth | |
700 | 1 | |a Jousse-Joulin, Sandrine |e investigator |4 oth | |
700 | 1 | |a Lauwerys, Bernard |e investigator |4 oth | |
700 | 1 | |a Ducreux, Julie |e investigator |4 oth | |
700 | 1 | |a Maudoux, Anne-Lise |e investigator |4 oth | |
700 | 1 | |a Vasconcelos, Carlos |e investigator |4 oth | |
700 | 1 | |a Tavares, Ana |e investigator |4 oth | |
700 | 1 | |a Neves, Esmeralda |e investigator |4 oth | |
700 | 1 | |a Faria, Raquel |e investigator |4 oth | |
700 | 1 | |a Brandão, Mariana |e investigator |4 oth | |
700 | 1 | |a Campar, Ana |e investigator |4 oth | |
700 | 1 | |a Marinho, António |e investigator |4 oth | |
700 | 1 | |a Farinha, Fátima |e investigator |4 oth | |
700 | 1 | |a Almeida, Isabel |e investigator |4 oth | |
700 | 1 | |a González-Gay, Miguel Ángel |e investigator |4 oth | |
700 | 1 | |a Blanco Alonso, Ricardo |e investigator |4 oth | |
700 | 1 | |a Corrales Martínez, Alfonso |e investigator |4 oth | |
700 | 1 | |a Cervera, Ricard |e investigator |4 oth | |
700 | 1 | |a Rodríguez-Pintó, Ignasi |e investigator |4 oth | |
700 | 1 | |a Espinosa, Gerard |e investigator |4 oth | |
700 | 1 | |a Lories, Rik |e investigator |4 oth | |
700 | 1 | |a De Langhe, Ellen |e investigator |4 oth | |
700 | 1 | |a Hunzelmann, Nicolas |e investigator |4 oth | |
700 | 1 | |a Belz, Doreen |e investigator |4 oth | |
700 | 1 | |a Witte, Torsten |e investigator |4 oth | |
700 | 1 | |a Baerlecken, Niklas |e investigator |4 oth | |
700 | 1 | |a Stummvoll, Georg |e investigator |4 oth | |
700 | 1 | |a Zauner, Michael |e investigator |4 oth | |
700 | 1 | |a Lehner, Michaela |e investigator |4 oth | |
700 | 1 | |a Collantes, Eduardo |e investigator |4 oth | |
700 | 1 | |a Ortega-Castro, Rafaela |e investigator |4 oth | |
700 | 1 | |a Aguirre-Zamorano, Angeles |e investigator |4 oth | |
700 | 1 | |a Escudero-Contreras, Alejandro |e investigator |4 oth | |
700 | 1 | |a Castro-Villegas, Carmen |e investigator |4 oth | |
700 | 1 | |a Jiménez Gómez, Yolanda |e investigator |4 oth | |
700 | 1 | |a Ortego, Norberto |e investigator |4 oth | |
700 | 1 | |a Concepción Fernández Roldán, María |e investigator |4 oth | |
700 | 1 | |a Raya, Enrique |e investigator |4 oth | |
700 | 1 | |a Jiménez Moleón, Inmaculada |e investigator |4 oth | |
700 | 1 | |a de Ramon, Enrique |e investigator |4 oth | |
700 | 1 | |a Quintero, Isabel Díaz |e investigator |4 oth | |
700 | 1 | |a Meroni, Pier Luigi |e investigator |4 oth | |
700 | 1 | |a Gerosa, Maria |e investigator |4 oth | |
700 | 1 | |a Schioppo, Tommaso |e investigator |4 oth | |
700 | 1 | |a Artusi, Carolina |e investigator |4 oth | |
700 | 1 | |a Chizzolini, Carlo |e investigator |4 oth | |
700 | 1 | |a Dufour, Aleksandra |e investigator |4 oth | |
700 | 1 | |a Wynar, Donatienne |e investigator |4 oth | |
700 | 1 | |a Kovács, Laszló |e investigator |4 oth | |
700 | 1 | |a Balog, Attila |e investigator |4 oth | |
700 | 1 | |a Deák, Magdolna |e investigator |4 oth | |
700 | 1 | |a Dulic, Sonja |e investigator |4 oth | |
700 | 1 | |a Kádár, Gabriella |e investigator |4 oth | |
700 | 1 | |a Hiepe, Falk |e investigator |4 oth | |
700 | 1 | |a Gerl, Velia |e investigator |4 oth | |
700 | 1 | |a Thiel, Silvia |e investigator |4 oth | |
700 | 1 | |a Rodriguez Maresca, Manuel |e investigator |4 oth | |
700 | 1 | |a López-Berrio, Antonio |e investigator |4 oth | |
700 | 1 | |a Aguilar-Quesada, Rocío |e investigator |4 oth | |
700 | 1 | |a Navarro-Linares, Héctor |e investigator |4 oth | |
700 | 1 | |a Ioannou, Yiannis |e investigator |4 oth | |
700 | 1 | |a Chamberlain, Chris |e investigator |4 oth | |
700 | 1 | |a Marovac, Jacqueline |e investigator |4 oth | |
700 | 1 | |a Alarcón Riquelme, Marta |e investigator |4 oth | |
700 | 1 | |a Gomes Anjos, Tania |e investigator |4 oth | |
700 | 1 | |a Beretta, Lorenzo |e investigator |4 oth | |
700 | 1 | |a Pers, Jacques-Olivier |e investigator |4 oth | |
700 | 1 | |a Saraux, Alain |e investigator |4 oth | |
700 | 1 | |a Vasconcelos, Carlos |e investigator |4 oth | |
700 | 1 | |a Cervera, Ricard |e investigator |4 oth | |
700 | 1 | |a Rodríguez-Pintó, Ignasi |e investigator |4 oth | |
700 | 1 | |a Lories, Rik |e investigator |4 oth | |
700 | 1 | |a De Langhe, Ellen |e investigator |4 oth | |
700 | 1 | |a Witte, Torsten |e investigator |4 oth | |
700 | 1 | |a Collantes, Eduardo |e investigator |4 oth | |
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700 | 1 | |a Jiménez Gómez, Yolanda |e investigator |4 oth | |
700 | 1 | |a Chizzolini, Carlo |e investigator |4 oth | |
700 | 1 | |a Kovács, Laszló |e investigator |4 oth | |
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