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3. Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Author

Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. ADBD - Anàlisi de Dades Complexes per a les Decisions Empresarials, Hernández Molina, Gabriela, Kostov, Belchin Adriyanov, Brito Zerón, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaèle, Szántó, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Acar Denizli, Nihan, Universitat Politècnica de Catalunya. Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya. ADBD - Anàlisi de Dades Complexes per a les Decisions Empresarials, Hernández Molina, Gabriela, Kostov, Belchin Adriyanov, Brito Zerón, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaèle, Szántó, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, and Acar Denizli, Nihan

Abstract

Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11¿966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57¿years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n¿=¿197), followed by diffuse large B-cell lymphoma (DLBCL) (n¿=¿67), nodal MZL lymphoma (n¿=¿29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n¿=¿19) and follicular lymphoma (FL) (n¿=¿17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8¿years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%., Peer Reviewed, Postprint (published version)

Published
2023

4. CCR9/CXCR5 Co-Expressing CD4 T Cells Are Increased in Primary Sjögren’s Syndrome and Are Enriched in PD-1/ICOS-Expressing Effector T Cells

Author

CTI, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Onderzoek Reumatologie, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, Hinrichs, Anneline C., Kruize, Aike A., Lafeber, Floris P.J.G., Leavis, Helen L., van Roon, Joel A.G., CTI, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Onderzoek Reumatologie, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, Hinrichs, Anneline C., Kruize, Aike A., Lafeber, Floris P.J.G., Leavis, Helen L., and van Roon, Joel A.G.

Published
2023

5. Deciphering the role of cDC2s in Sjögren's syndrome: transcriptomic profile links altered antigen processes with IFN signature and autoimmunity

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Reumat./Klin. Immunologie, CTI Pandit, MS Reumatologie/Immunologie/Infectie, Lopes, Ana P, Hillen, Maarten R, Hinrichs, Anneline C, Blokland, Sofie Lm, Bekker, Cornelis Pj, Pandit, Aridaman, Kruize, Aike A, Radstake, Timothy Rdj, van Roon, Joel A, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Reumat./Klin. Immunologie, CTI Pandit, MS Reumatologie/Immunologie/Infectie, Lopes, Ana P, Hillen, Maarten R, Hinrichs, Anneline C, Blokland, Sofie Lm, Bekker, Cornelis Pj, Pandit, Aridaman, Kruize, Aike A, Radstake, Timothy Rdj, and van Roon, Joel A

Published
2023

6. Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis

Author

CTI Meyaard, Oogheelkunde Onderzoek, CTI Lab support, Translationele immunologie, DBG Metabole en Endocriene Ziekten, Onderzoek Reumatologie, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, MS Oogheelkunde, Child Health, CTI Boes, Onderzoek, CTI Pandit, Servaas, Nila H, Hiddingh, Sanne, Chouri, Eleni, Wichers, Catharina G K, Affandi, Alsya J, Ottria, Andrea, Bekker, Cornelis P J, Cossu, Marta, Silva-Cardoso, Sandra C, van der Kroef, Maarten, Hinrichs, Anneline C, Carvalheiro, Tiago, Vazirpanah, Nadia, Beretta, Lorenzo, Rossato, Marzia, Bonte-Mineur, Femke, Radstake, Timothy R D J, Kuiper, Jonas J W, Boes, Marianne, Pandit, Aridaman, CTI Meyaard, Oogheelkunde Onderzoek, CTI Lab support, Translationele immunologie, DBG Metabole en Endocriene Ziekten, Onderzoek Reumatologie, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, MS Oogheelkunde, Child Health, CTI Boes, Onderzoek, CTI Pandit, Servaas, Nila H, Hiddingh, Sanne, Chouri, Eleni, Wichers, Catharina G K, Affandi, Alsya J, Ottria, Andrea, Bekker, Cornelis P J, Cossu, Marta, Silva-Cardoso, Sandra C, van der Kroef, Maarten, Hinrichs, Anneline C, Carvalheiro, Tiago, Vazirpanah, Nadia, Beretta, Lorenzo, Rossato, Marzia, Bonte-Mineur, Femke, Radstake, Timothy R D J, Kuiper, Jonas J W, Boes, Marianne, and Pandit, Aridaman

Published
2023

7. Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c + Dendritic Cell Dysregulation in Systemic Sclerosis

Author

Servaas, Nila H., primary, Hiddingh, Sanne, additional, Chouri, Eleni, additional, Wichers, Catharina G. K., additional, Affandi, Alsya J., additional, Ottria, Andrea, additional, Bekker, Cornelis P. J., additional, Cossu, Marta, additional, Silva‐Cardoso, Sandra C., additional, van der Kroef, Maarten, additional, Hinrichs, Anneline C., additional, Carvalheiro, Tiago, additional, Vazirpanah, Nadia, additional, Beretta, Lorenzo, additional, Rossato, Marzia, additional, Bonte‐Mineur, Femke, additional, Radstake, Timothy R. D. J., additional, Kuiper, Jonas J. W., additional, Boes, Marianne, additional, and Pandit, Aridaman, additional

Published
2022
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11. Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies

Author

Hernandez-Molina, Gabriela, Kostov, Belchin, Brito-Zeron, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaele, Szanto, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Rasmussen, Astrid, Solans-Laque, Roser, Hofauer, Benedikt, Sene, Damien, Pasoto, Sandra G., Rischmueller, Maureen, Praprotnik, Sonja, Gheita, Tamer A., Danda, Debashish, Armagan, Berkan, Suzuki, Yasunori, Valim, Valeria, Devauchelle-Pensec, Valerie, Retamozo, Soledad, Kvarnstrom, Marika, Sebastian, Agata, Atzeni, Fabiola, Giacomelli, Roberto, Carsons, Steven E., Kwok, Seung-Ki, Nakamura, Hideki, Moca Trevisani, Virginia Fernandes, Flores-Chavez, Alejandra, Mariette, Xavier, Ramos-Casals, Manuel, Hernandez-Molina, Gabriela, Kostov, Belchin, Brito-Zeron, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C., Quartuccio, Luca, Baldini, Chiara, Seror, Raphaele, Szanto, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Rasmussen, Astrid, Solans-Laque, Roser, Hofauer, Benedikt, Sene, Damien, Pasoto, Sandra G., Rischmueller, Maureen, Praprotnik, Sonja, Gheita, Tamer A., Danda, Debashish, Armagan, Berkan, Suzuki, Yasunori, Valim, Valeria, Devauchelle-Pensec, Valerie, Retamozo, Soledad, Kvarnstrom, Marika, Sebastian, Agata, Atzeni, Fabiola, Giacomelli, Roberto, Carsons, Steven E., Kwok, Seung-Ki, Nakamura, Hideki, Moca Trevisani, Virginia Fernandes, Flores-Chavez, Alejandra, Mariette, Xavier, and Ramos-Casals, Manuel

Abstract

Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n = 67), nodal MZL lymphoma (n = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n = 19) and follicular lymphoma (FL) (n = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%.

Published
2022
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12. CCL5 Release by CCR9+ CD8 T Cells: A Potential Contributor to Immunopathology of Primary Sjögren’s Syndrome

Author

CTI, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Reumat./Klin. Immunologie, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, Hinrichs, Anneline C., Blokland, Sofie L.M., Kruize, Aike A., Lafeber, Floris P.J., Leavis, Helen L., van Roon, Joel A.G., CTI, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Reumat./Klin. Immunologie, MS Reumatologie/Immunologie/Infectie, Regenerative Medicine and Stem Cells, Hinrichs, Anneline C., Blokland, Sofie L.M., Kruize, Aike A., Lafeber, Floris P.J., Leavis, Helen L., and van Roon, Joel A.G.

Published
2022

14. Nuclear Receptor Subfamily 4A Signaling as a Key Disease Pathway of CD1c+ Dendritic Cell Dysregulation in Systemic Sclerosis.

Author

Servaas, Nila H., Hiddingh, Sanne, Chouri, Eleni, Wichers, Catharina G. K., Affandi, Alsya J., Ottria, Andrea, Bekker, Cornelis P. J., Cossu, Marta, Silva‐Cardoso, Sandra C., van der Kroef, Maarten, Hinrichs, Anneline C., Carvalheiro, Tiago, Vazirpanah, Nadia, Beretta, Lorenzo, Rossato, Marzia, Bonte‐Mineur, Femke, Radstake, Timothy R. D. J., Kuiper, Jonas J. W., Boes, Marianne, and Pandit, Aridaman

Subjects
DENDRITIC cells, IN vitro studies, CYTOKINES, HOMEOSTASIS, SEQUENCE analysis, SYSTEMIC scleroderma, CELL receptors, PRECIPITIN tests, CULTURES (Biology), CELLULAR signal transduction, GENE expression profiling, GENES, T cells, SYMPTOMS
Abstract

Objective: This study was undertaken to identify key disease pathways driving conventional dendritic cell (cDC) alterations in systemic sclerosis (SSc). Methods: Transcriptomic profiling was performed on peripheral blood CD1c+ cDCs (cDC2s) isolated from 12 healthy donors and 48 patients with SSc, including all major disease subtypes. We performed differential expression analysis for the different SSc subtypes and healthy donors to uncover genes dysregulated in SSc. To identify biologically relevant pathways, we built a gene coexpression network using weighted gene correlation network analysis. We validated the role of key transcriptional regulators using chromatin immunoprecipitation (ChIP) sequencing and in vitro functional assays. Results: We identified 17 modules of coexpressed genes in cDCs that correlated with SSc subtypes and key clinical traits, including autoantibodies, skin score, and occurrence of interstitial lung disease. A module of immunoregulatory genes was markedly down‐regulated in patients with the diffuse SSc subtype characterized by severe fibrosis. Transcriptional regulatory network analysis performed on this module predicted nuclear receptor 4A (NR4A) subfamily genes (NR4A1, NR4A2, NR4A3) as the key transcriptional regulators of inflammation. Indeed, ChIP‐sequencing analysis indicated that these NR4A members target numerous differentially expressed genes in SSc cDC2s. Inclusion of NR4A receptor agonists in culture‐based experiments provided functional proof that dysregulation of NR4As affects cytokine production by cDC2s and modulates downstream T cell activation. Conclusion: NR4A1, NR4A2, and NR4A3 are important regulators of immunosuppressive and fibrosis‐associated pathways in SSc cDCs. Thus, the NR4A family represents novel potential targets to restore cDC homeostasis in SSc. [ABSTRACT FROM AUTHOR]

Published
2023
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15. Characterization and outcomes of 414 patients with primary SS who developed haematological malignancies.

Author

Hernández-Molina, Gabriela, Kostov, Belchin, Brito-Zerón, Pilar, Vissink, Arjan, Mandl, Thomas, Hinrichs, Anneline C, Quartuccio, Luca, Baldini, Chiara, Seror, Raphaele, Szántó, Antonia, Isenberg, David, Gerli, Roberto, Nordmark, Gunnel, Rasmussen, Astrid, Solans-Laque, Roser, Hofauer, Benedikt, Sène, Damien, Pasoto, Sandra G, Rischmueller, Maureen, and Praprotnik, Sonja

Subjects
LYMPHOID tissue, DISEASE relapse, HEMATOLOGIC malignancies, SJOGREN'S syndrome, LYMPHOMAS, LYMPHOPROLIFERATIVE disorders, SYMPTOMS
Abstract

Objective To characterize 414 patients with primary SS who developed haematological malignancies and to analyse how the main SS- and lymphoma-related features can modify the presentation patterns and outcomes. Methods By January 2021, the Big Data Sjögren Project Consortium database included 11 966 patients fulfilling the 2002/2016 classification criteria. Haematological malignancies diagnosed according to the World Health Organization (WHO) classification were retrospectively identified. Results There were 414 patients (355 women, mean age 57 years) with haematological malignancies (in 43, malignancy preceded at least one year the SS diagnosis). A total of 376 (91%) patients had mature B-cell malignancy, nearly half had extranodal marginal zone lymphoma (MZL) of mucosa-associated lymphoid tissue (MALT lymphoma) (n  = 197), followed by diffuse large B-cell lymphoma (DLBCL) (n  = 67), nodal MZL lymphoma (n  = 29), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (n  = 19) and follicular lymphoma (FL) (n  = 17). Rates of complete response, relapses and death were 80%, 34% and 13%, respectively, with a 5-year survival rate of 86.5% after a mean follow-up of 8 years. There were significant differences in age at diagnosis (younger in MALT, older in CLL/SLL), predominant clinical presentation (glandular enlargement in MALT lymphoma, peripheral lymphadenopathy in nodal MZL and FL, constitutional symptoms in DLBCL, incidental diagnosis in CLL/SLL), therapeutic response (higher in MALT lymphoma, lower in DLBCL) and survival (better in MALT, nodal MZL and FL, worse in DLBCL). Conclusion In the largest reported study of haematological malignancies complicating primary SS, we confirm the overwhelming predominance of B-cell lymphomas, especially MALT, with the salivary glands being the primary site of involvement. This highly-specific histopathological scenario is linked with the overall good prognosis with a 5-year survival rate of nearly 90%. [ABSTRACT FROM AUTHOR]

Published
2023
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16. The Transcriptomic Profile of Monocytes from Patients With Sjögren’s Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators

Author

Lopes, Ana P., primary, Bekker, Cornelis P. J., additional, Hillen, Maarten R., additional, Blokland, Sofie L. M., additional, Hinrichs, Anneline C., additional, Pandit, Aridaman, additional, Kruize, Aike A., additional, Radstake, Timothy R. D. J., additional, and van Roon, Joel A. G., additional

Published
2021
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18. The Transcriptomic Profile of Monocytes from Patients With Sjögren's Syndrome Is Associated With Inflammatory Parameters and Is Mimicked by Circulating Mediators

Author

Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Translationele immunologie, Other research (not in main researchprogram), Unit Opleiding Aios, CTI Pandit, MS Reumatologie/Immunologie/Infectie, Lopes, Ana P, Bekker, Cornelis P J, Hillen, Maarten R, Blokland, Sofie L M, Hinrichs, Anneline C, Pandit, Aridaman, Kruize, Aike A, Radstake, Timothy R D J, van Roon, Joel A G, Infection & Immunity, Lab Reumatologie/Klinische Immunologie, Translationele immunologie, Other research (not in main researchprogram), Unit Opleiding Aios, CTI Pandit, MS Reumatologie/Immunologie/Infectie, Lopes, Ana P, Bekker, Cornelis P J, Hillen, Maarten R, Blokland, Sofie L M, Hinrichs, Anneline C, Pandit, Aridaman, Kruize, Aike A, Radstake, Timothy R D J, and van Roon, Joel A G

Published
2021

19. Transcriptome Analysis of CCR9+ T Helper Cells From Primary Sjögren's Syndrome Patients Identifies CCL5 as a Novel Effector Molecule

Author

Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Aios, DBG Metabole en Endocriene Ziekten, MS Reumatologie/Immunologie/Infectie, CTI Pandit, Hinrichs, Anneline C, Blokland, Sofie L M, Lopes, Ana P, Wichers, Catharina G K, Kruize, Aike A, Pandit, Aridaman, Radstake, Timothy R D J, van Roon, Joel A G, Lab Reumatologie/Klinische Immunologie, Infection & Immunity, Unit Opleiding Aios, DBG Metabole en Endocriene Ziekten, MS Reumatologie/Immunologie/Infectie, CTI Pandit, Hinrichs, Anneline C, Blokland, Sofie L M, Lopes, Ana P, Wichers, Catharina G K, Kruize, Aike A, Pandit, Aridaman, Radstake, Timothy R D J, and van Roon, Joel A G

Published
2021

20. Angiopoietin-2 Promotes Inflammatory Activation in Monocytes of Systemic Sclerosis Patients

Author

Carvalheiro, Tiago, primary, Lopes, Ana P., additional, van der Kroef, Maarten, additional, Malvar-Fernandez, Beatriz, additional, Rafael-Vidal, Carlos, additional, Hinrichs, Anneline C., additional, Servaas, Nila H., additional, Bonte-Mineur, Femke, additional, Kok, Marc R., additional, Beretta, Lorenzo, additional, Zimmermann, Maili, additional, Marut, Wioleta, additional, Pego-Reigosa, Jose M., additional, Radstake, Timothy R. D. J., additional, and Garcia, Samuel, additional

Published
2020
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21. Angiopoietin-2 Promotes Inflammatory Activation in Monocytes of Systemic Sclerosis Patients

Author

CTI Meyaard, Infection & Immunity, Translationele immunologie, Other research (not in main researchprogram), Lab Reumatologie/Klinische Immunologie, CTI Pandit, CTI Research, CTI Radstake, Carvalheiro, Tiago, Lopes, Ana P, van der Kroef, Maarten, Malvar-Fernandez, Beatriz, Rafael-Vidal, Carlos, Hinrichs, Anneline C, Servaas, Nila H, Bonte-Mineur, Femke, Kok, Marc R, Beretta, Lorenzo, Zimmermann, Maili, Marut, Wioleta, Pego-Reigosa, Jose M, Radstake, Timothy R D J, Garcia, Samuel, CTI Meyaard, Infection & Immunity, Translationele immunologie, Other research (not in main researchprogram), Lab Reumatologie/Klinische Immunologie, CTI Pandit, CTI Research, CTI Radstake, Carvalheiro, Tiago, Lopes, Ana P, van der Kroef, Maarten, Malvar-Fernandez, Beatriz, Rafael-Vidal, Carlos, Hinrichs, Anneline C, Servaas, Nila H, Bonte-Mineur, Femke, Kok, Marc R, Beretta, Lorenzo, Zimmermann, Maili, Marut, Wioleta, Pego-Reigosa, Jose M, Radstake, Timothy R D J, and Garcia, Samuel

Published
2020

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