Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome
Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these ab...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01153/full |
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| author | Armen Sanosyan Claire Daien Claire Daien Anaïz Nutz Karine Bollore Anne-Sophie Bedin Jacques Morel Jacques Morel Valérie Zimmermann Gaetane Nocturne Marianne Peries Nicolas Guigue Jacques-Eric Gottenberg Philippe Van de Perre Xavier Mariette Xavier Mariette Edouard Tuaillon |
| author_facet | Armen Sanosyan Claire Daien Claire Daien Anaïz Nutz Karine Bollore Anne-Sophie Bedin Jacques Morel Jacques Morel Valérie Zimmermann Gaetane Nocturne Marianne Peries Nicolas Guigue Jacques-Eric Gottenberg Philippe Van de Perre Xavier Mariette Xavier Mariette Edouard Tuaillon |
| author_sort | Armen Sanosyan |
| collection | DOAJ |
| description | Primary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these abnormalities are accompanied with disturbed systemic EBV control or have any association with pSS activity remains to be investigated. In this observational study, we initially explored anti-EBV antibodies and cell-free DNA in 395 samples from a cross-sectional plasma collection of pSS patients included in ASSESS French national cohort. Results were assessed in relation with disease activity. Further, to assess cell-associated EBV DNA we organized a case-control study including 20 blood samples from pSS patients followed in University Hospital Center of Montpellier. Results were compared with matched controls. Robust response against EBV early antigen (EA) was observed in pSS patients with anti-SSA/B (Sjögren's syndrome A and B) and anti-SSA autoantibodies compared to anti-SSA/B negatives (P < 0.01 and P = 0.01, respectively). Increased beta-2 microglobulin, kappa and lambda light chains, and immunoglobulin G levels were more frequently observed in anti-EA seropositive pSS subjects compared to anti-EA negative subjects (P < 0.001; P = 0.001; P = 0.003, respectively). Beta-2 microglobulin was independently associated with anti-EA positivity in multivariate analysis (P < 0.001). Plasma cell-free EBV DNA and EBV cellular reservoir was not different between pSS patients and controls. We conclude that serological evidence of EBV reactivation was more frequently observed and more strongly associated with anti-SSA/B status and B cell activation markers in pSS. However, serological profile of EBV reactivation was not accompanied by molecular evidence of systemic EBV reactivation. Our data indicated that EBV infection remains efficiently controlled in the blood of pSS patients. |
| first_indexed | 2024-12-19T05:26:46Z |
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| id | doaj.art-974785ea01b94b4eab4024ed6fa5f7b2 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-19T05:26:46Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-974785ea01b94b4eab4024ed6fa5f7b22022-12-21T20:34:21ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01153446578Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's SyndromeArmen Sanosyan0Claire Daien1Claire Daien2Anaïz Nutz3Karine Bollore4Anne-Sophie Bedin5Jacques Morel6Jacques Morel7Valérie Zimmermann8Gaetane Nocturne9Marianne Peries10Nicolas Guigue11Jacques-Eric Gottenberg12Philippe Van de Perre13Xavier Mariette14Xavier Mariette15Edouard Tuaillon16Pathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FranceCHU Montpellier, Department of Rheumatology, Montpellier, FranceInstitut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR 5535, Université de Montpellier, Montpellier, FranceCHRU de Nîmes, Nîmes, FrancePathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FrancePathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FranceCHU Montpellier, Department of Rheumatology, Montpellier, FranceInstitut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR 5535, Université de Montpellier, Montpellier, FranceInstitut de Génétique Moléculaire de Montpellier, Centre National de la Recherche Scientifique UMR 5535, Université de Montpellier, Montpellier, FranceFaculté de Médecine, Université Paris Sud, INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, FrancePathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FranceGroupe Hospitalier Saint-Louis-Lariboisière-Fernand-Widal, Laboratory of Parasitology and Mycology, AP-HP, Paris, FranceRheumatology Department, CHU Strasbourg, Strasbourg, FrancePathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FranceFaculté de Médecine, Université Paris Sud, INSERM, U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin-Bicêtre, FranceService de Rhumatologie AP-HP, Hôpital Bicêtre, Le Kremlin-Bicêtre, FrancePathogenesis and Control of Chronic Infections, University of Montpellier, INSERM, EFS, CHU Montpellier, Montpellier, FrancePrimary Sjögren's syndrome (pSS) is characterized by B cell hyperactivation, production of autoantibodies and increased risk of B cell lymphomas. Serological profile of Epstein-Barr virus (EBV) reactivation and increase EBV DNA levels in exocrine glands are observed in pSS, but whether these abnormalities are accompanied with disturbed systemic EBV control or have any association with pSS activity remains to be investigated. In this observational study, we initially explored anti-EBV antibodies and cell-free DNA in 395 samples from a cross-sectional plasma collection of pSS patients included in ASSESS French national cohort. Results were assessed in relation with disease activity. Further, to assess cell-associated EBV DNA we organized a case-control study including 20 blood samples from pSS patients followed in University Hospital Center of Montpellier. Results were compared with matched controls. Robust response against EBV early antigen (EA) was observed in pSS patients with anti-SSA/B (Sjögren's syndrome A and B) and anti-SSA autoantibodies compared to anti-SSA/B negatives (P < 0.01 and P = 0.01, respectively). Increased beta-2 microglobulin, kappa and lambda light chains, and immunoglobulin G levels were more frequently observed in anti-EA seropositive pSS subjects compared to anti-EA negative subjects (P < 0.001; P = 0.001; P = 0.003, respectively). Beta-2 microglobulin was independently associated with anti-EA positivity in multivariate analysis (P < 0.001). Plasma cell-free EBV DNA and EBV cellular reservoir was not different between pSS patients and controls. We conclude that serological evidence of EBV reactivation was more frequently observed and more strongly associated with anti-SSA/B status and B cell activation markers in pSS. However, serological profile of EBV reactivation was not accompanied by molecular evidence of systemic EBV reactivation. Our data indicated that EBV infection remains efficiently controlled in the blood of pSS patients.https://www.frontiersin.org/article/10.3389/fimmu.2019.01153/fullprimary Sjögren's syndromeEpstein-Barr virusanti-EA antibodiesEBV DNAbeta-2 microglobulinautoantibodies |
| spellingShingle | Armen Sanosyan Claire Daien Claire Daien Anaïz Nutz Karine Bollore Anne-Sophie Bedin Jacques Morel Jacques Morel Valérie Zimmermann Gaetane Nocturne Marianne Peries Nicolas Guigue Jacques-Eric Gottenberg Philippe Van de Perre Xavier Mariette Xavier Mariette Edouard Tuaillon Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome Frontiers in Immunology primary Sjögren's syndrome Epstein-Barr virus anti-EA antibodies EBV DNA beta-2 microglobulin autoantibodies |
| title | Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome |
| title_full | Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome |
| title_fullStr | Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome |
| title_full_unstemmed | Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome |
| title_short | Discrepancy of Serological and Molecular Patterns of Circulating Epstein-Barr Virus Reactivation in Primary Sjögren's Syndrome |
| title_sort | discrepancy of serological and molecular patterns of circulating epstein barr virus reactivation in primary sjogren s syndrome |
| topic | primary Sjögren's syndrome Epstein-Barr virus anti-EA antibodies EBV DNA beta-2 microglobulin autoantibodies |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01153/full |
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