Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus
Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, ty...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-12-01
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| Series: | Journal of Translational Autoimmunity |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589909024000169 |
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| author | Ellen D. Kaan Tammo E. Brunekreef Julia Drylewicz Lucas L. van den Hoogen Maarten van der Linden Helen L. Leavis Jacob M. van Laar Michiel van der Vlist Henny G. Otten Maarten Limper |
| author_facet | Ellen D. Kaan Tammo E. Brunekreef Julia Drylewicz Lucas L. van den Hoogen Maarten van der Linden Helen L. Leavis Jacob M. van Laar Michiel van der Vlist Henny G. Otten Maarten Limper |
| author_sort | Ellen D. Kaan |
| collection | DOAJ |
| description | Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE. Methods: We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity. Results: We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = −0.530; p = 0.007) and anti-PmScl100 (r = −0.445; p = 0.03). Conclusion: We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature. |
| format | Article |
| id | doaj-art-04b3c7987a8e4c35b53ca455a1fda635 |
| institution | OA Journals |
| issn | 2589-9090 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Translational Autoimmunity |
| spelling | doaj-art-04b3c7987a8e4c35b53ca455a1fda6352025-08-20T01:59:34ZengElsevierJournal of Translational Autoimmunity2589-90902024-12-01910024610.1016/j.jtauto.2024.100246Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosusEllen D. Kaan0Tammo E. Brunekreef1Julia Drylewicz2Lucas L. van den Hoogen3Maarten van der Linden4Helen L. Leavis5Jacob M. van Laar6Michiel van der Vlist7Henny G. Otten8Maarten Limper9Center for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Oncode Institute, Utrecht, the NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Oncode Institute, Utrecht, the NetherlandsCenter for Translational Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Central Diagnostic Laboratory, University Medical Center Utrecht, Utrecht University, Utrecht, the NetherlandsDepartment of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands; Corresponding author. Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, P.O. Box 85500, 3508, GA, Utrecht, the Netherlands.Objective: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of disease symptoms and an unpredictable clinical course. To improve treatment outcome, stratification based on immunological manifestations commonly seen in patients with SLE such as autoantibodies, type I interferon (IFN) signature and neutrophil extracellular trap (NET) release may help. It is assumed that there is an association between these immunological phenomena, since NET release induces IFN production and IFN induces autoantibody formation via B-cell activation. Here we studied the association between autoantibodies, the IFN signature, NET release, and clinical manifestations in patients with SLE. Methods: We performed principal component analysis (PCA) and hierarchical clustering of 57 SLE-related autoantibodies in 25 patients with SLE. We correlated each autoantibody to the IFN signature and NET inducing capacity. Results: We observed two distinct clusters: one cluster contained mostly patients with a high IFN signature. Patients in this cluster often present with cutaneous lupus, and have higher anti-dsDNA concentrations. Another cluster contained a mix of patients with a high and low IFN signature. Patients with high and low NET inducing capacity were equally distributed between the clusters. Variance between the clusters is mainly driven by antibodies against histones, RibP2, RibP0, EphB2, RibP1, PCNA, dsDNA, and nucleosome. In addition, we found a trend towards increased concentrations of autoantibodies against EphB2, RibP1, and RNP70 in patients with an IFN signature. We found a negative correlation of NET inducing capacity with anti-FcER (r = −0.530; p = 0.007) and anti-PmScl100 (r = −0.445; p = 0.03). Conclusion: We identified a subgroup of patients with an IFN signature that express increased concentrations of antibodies against DNA and RNA-binding proteins, which can be useful for further patient stratification and a more targeted therapy. We did not find positive associations between autoantibodies and NET inducing capacity. Our study further strengthens the evidence of a correlation between RNA-binding autoantibodies and the IFN signature.http://www.sciencedirect.com/science/article/pii/S2589909024000169Systemic lupus erythematosusAutoantibodiesInterferon signatureNETosisPatient stratification |
| spellingShingle | Ellen D. Kaan Tammo E. Brunekreef Julia Drylewicz Lucas L. van den Hoogen Maarten van der Linden Helen L. Leavis Jacob M. van Laar Michiel van der Vlist Henny G. Otten Maarten Limper Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus Journal of Translational Autoimmunity Systemic lupus erythematosus Autoantibodies Interferon signature NETosis Patient stratification |
| title | Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus |
| title_full | Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus |
| title_fullStr | Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus |
| title_full_unstemmed | Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus |
| title_short | Association of autoantibodies with the IFN signature and NETosis in patients with systemic lupus erythematosus |
| title_sort | association of autoantibodies with the ifn signature and netosis in patients with systemic lupus erythematosus |
| topic | Systemic lupus erythematosus Autoantibodies Interferon signature NETosis Patient stratification |
| url | http://www.sciencedirect.com/science/article/pii/S2589909024000169 |
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