Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish SLE patients
Rheumatology, 2024
Elbagir S., Mohammed N., Oke V., Larsson A., Nilsson J., Elshafie A., Elagib E., Nur M., Gunnarsson I., Svenungsson E., Rönnelid J.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
Immunological & Inflammatory Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
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 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 sub-specificities: 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 the Proximity Extension Assay technique or ELISA.
Results
Among Sudanese patients, the investigated antibodies were 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 were associated with CXCL10 and S100A12, but in multivariate analyses, unlike anti-histone, associations lost significance.
Among Swedish patients, MCP-1, CXCL10, and 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 origins, 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 the main drivers of type-1 interferon activity in SLE.