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. 2025 Mar 1;64(3):1170-1178.
doi: 10.1093/rheumatology/keae134.

Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish SLE patients

Sahwa Elbagir  1 , NasrEldeen A Mohammed  2 , Vilija Oke  3   4 , Anders Larsson  5 , Jan Nilsson  6 , Amir Elshafie  1   7 , Elnour M Elagib  8 , Musa A M Nur  9 , Iva Gunnarsson  3 , Elisabet Svenungsson  3 , Johan Rönnelid  1
Affiliations

Anti-histone and anti-nucleosome rather than anti-dsDNA antibodies associate with IFN-induced biomarkers in Sudanese and Swedish SLE patients

Sahwa Elbagir et al. Rheumatology (Oxford). .

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.

Keywords: Africa; SLE; anti-chromatin antibodies; anti-dsDNA; interferon; proteome analysis.

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Figures

Figure 1.
Figure 1.
Volcano plot showing distribution of 72 inflammatory proteins in Sudanese cohort. Comparisons in SLE patients (n = 93) vs controls (n = 104), (A), and in patients positive for any ANA-associated autoantibody (n = 63) vs autoantibody negative patients (n = 30), (B). Significant protein level differences are demonstrated above the dotted line which represent FDR LogWorth with P-value <0.05. Benjamini-Hochberg method was used to correct for multiple testing. The X-axis represent the difference in means comparisons of studied proteins
See this image and copyright information in PMC

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