Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish Systemic Lupus Erythematosus patients
© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology..
OBJECTIVES: In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines.
METHODS: We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192). Autoantibodies targeting ANA-subspecificites: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with Proximity Extension Assay technique or ELISA.
RESULTS: Among Sudanese patients, the investigated antibodies significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.Among Swedish patients, MCP-1, CXCL10, SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared with anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant.
CONCLUSION: In two cohorts of different ethnical origin, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be main drivers of type-1 interferon activity in SLE.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - year:2024 |
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| Enthalten in: |
Rheumatology (Oxford, England) - (2024) vom: 09. März |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Elbagir, Sahwa [VerfasserIn] |
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| Links: |
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| Themen: |
Africa |
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| Anmerkungen: |
Date Revised 09.03.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1093/rheumatology/keae134 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369499107 |
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| 100 | 1 | |a Elbagir, Sahwa |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish Systemic Lupus Erythematosus patients |
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| 500 | |a Date Revised 09.03.2024 | ||
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| 500 | |a Citation Status Publisher | ||
| 520 | |a © The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology. | ||
| 520 | |a OBJECTIVES: In SLE, anti-dsDNA can co-occur with autoantibodies against other chromatin components, like histones and nucleosomes. These antibodies induce type-1 interferon production, a hallmark of SLE. We measured antinuclear antibody (ANA) sub-specificities and investigated their associations to inflammatory biomarkers including interferon-regulated chemokines | ||
| 520 | |a METHODS: We included 93 Sudanese and 480 Swedish SLE patients and matched controls (N = 104 + 192). Autoantibodies targeting ANA-subspecificites: dsDNA, Sm, Sm/U1RNPcomplex, U1RNP, SSA/Ro52, SSA/Ro60, SSB/La, ribosomal P, PCNA and histones were quantified in all subjects, anti-nucleosome only in the Swedish patients, with a bead-based multiplex immunoassay. Levels of 72 plasma biomarkers were determined with Proximity Extension Assay technique or ELISA | ||
| 520 | |a RESULTS: Among Sudanese patients, the investigated antibodies significantly associated with 9/72 biomarkers. Anti-histone antibodies showed the strongest positive correlations with MCP-3 and S100A12 as well as with interferon I-inducible factors MCP-1 and CXCL10. Anti-dsDNA antibodies associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.Among Swedish patients, MCP-1, CXCL10, SA100A12 also demonstrated stronger associations to anti-histone and anti-nucleosome antibodies, compared with anti-dsDNA and other ANA sub-specificities. In multiple regression models, anti-histone/nucleosome retained the strongest associations. When excluding anti-histone or anti-nucleosome positive patients, the associations between MCP-1/CXCL10 and anti-dsDNA were lost. In contrast, when excluding anti-dsDNA positive patients, associations with anti-histone and anti-nucleosome remained significant | ||
| 520 | |a CONCLUSION: In two cohorts of different ethnical origin, autoantibodies targeting chromatin correlate stronger with IFN-induced inflammatory biomarkers than anti-dsDNA or other ANA sub-specificities. Our results suggest that anti-histone/nucleosome autoantibodies may be main drivers of type-1 interferon activity in SLE | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Africa | |
| 650 | 4 | |a Anti-chromatin antibodies | |
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| 650 | 4 | |a interferon | |
| 650 | 4 | |a proteome analysis | |
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| 700 | 1 | |a Oke, Vilija |e verfasserin |4 aut | |
| 700 | 1 | |a Larsson, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Nilsson, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Elshafie, Amir |e verfasserin |4 aut | |
| 700 | 1 | |a Elagib, Elnour M |e verfasserin |4 aut | |
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| 700 | 1 | |a Rönnelid, Johan |e verfasserin |4 aut | |
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