Accumulation of antinuclear associated antibodies in circulating immune complexes is more prominent in SLE patients from Sudan than Sweden

Elbagir, Sahwa; Sohrabian, Azita; Elshafie, Amir I.; Elagib, Elnour Mohammed; Mohammed, NasrEldeen A; Nur, Musa A. M.; Svenungsson, Elisabet; Gunnarsson, Iva; Rönnelid, Johan

doi:10.1038/s41598-020-78213-5

Cited by 4 publications

(1 citation statement)

References 27 publications

(29 reference statements)

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“…The pathophysiology of SLE is complex and predominantly caused by an inflammatory response to immunogenic endogenous chromatin, acting as a damage-associated molecular pattern [ 50 ]. In SLE patients, the chromatin accumulates due to insufficient DNA clearance [ 51 ].…”

Section: The Role Of Aberrant Dna Methylation In the Pathogenesis Of Slementioning

confidence: 99%

Lupus, DNA Methylation, and Air Pollution: A Malicious Triad

Rasking

Roelens

Sprangers

et al. 2022

IJERPH

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The pathogenesis of systemic lupus erythematosus (SLE) remains elusive to this day; however, genetic, epigenetic, and environmental factors have been implicated to be involved in disease pathogenesis. Recently, it was demonstrated that in systemic lupus erythematosus (SLE) patients, interferon-regulated genes are hypomethylated in naïve CD4+ T cells, CD19+ B lymphocytes, and CD14+ monocytes. This suggests that interferon-regulated genes may have been epigenetically poised in SLE patients for rapid expression upon stimulation by different environmental factors. Additionally, environmental studies have identified DNA (hypo)methylation changes as a potential mechanism of environmentally induced health effects in utero, during childhood and in adults. Finally, epidemiologic studies have firmly established air pollution as a crucial SLE risk factor, as studies showed an association between fine particulate matter (PM2.5) and traditional SLE biomarkers related to disease flare, hospital admissions, and an increased SLEDAI score. In this review, the relationship between aberrant epigenetic regulation, the environment, and the development of SLE will be discussed.

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Section: The Role Of Aberrant Dna Methylation In the Pathogenesis Of Slementioning

confidence: 99%

Lupus, DNA Methylation, and Air Pollution: A Malicious Triad

Rasking

Roelens

Sprangers

et al. 2022

IJERPH

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Anti-Sm antibodies in the classification criteria of systemic lupus erythematosus

Beers

Schreurs

2022

Journal of Translational Autoimmunity

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

Elbagir,

Mohammed,

Oke

et al. 2024

Rheumatology

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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.

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Accumulation of antinuclear associated antibodies in circulating immune complexes is more prominent in SLE patients from Sudan than Sweden

Cited by 4 publications

References 27 publications

Lupus, DNA Methylation, and Air Pollution: A Malicious Triad

Lupus, DNA Methylation, and Air Pollution: A Malicious Triad

Anti-Sm antibodies in the classification criteria of systemic lupus erythematosus

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

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