Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Feb 7;16(1):R48.
doi: 10.1186/ar4477.

Serum nitrated nucleosome levels in patients with systemic lupus erythematosus: a retrospective longitudinal cohort study

Sara Croca, Paul Bassett, Charis Pericleous, Karim Fouad Alber, David Latchman, David Isenberg, Ian Giles, Anisur Rahman, Yiannis Ioannou

Serum nitrated nucleosome levels in patients with systemic lupus erythematosus: a retrospective longitudinal cohort study

Sara Croca et al. Arthritis Res Ther. .

Abstract

Introduction: Circulating nucleosomes released from apoptotic cells are important in the pathogenesis of systemic lupus erythematosus (SLE). Both nucleosomes and anti-nucleosome antibodies are deposited in inflamed tissues in patients with SLE. Active inflammation promotes nitration of tyrosine residues on serum proteins. Our hypothesis was that levels of nitrated nucleosomes would be elevated in patients with SLE and could be associated with disease activity. We therefore carried out a retrospective longitudinal study to investigate factors affecting levels of nitrated nucleosomes (NN) in patients with SLE.

Methods: A novel serum ELISA was developed to measure serum NN and modified to measure serum nitrated albumin (NA). Levels of both NN and NA were measured in 397 samples from 49 patients with SLE followed through periods of disease flare and remission for a mean of 89 months. Anti-nucleosome antibody (anti-nuc) levels were measured in the same samples. The effects of 24 different clinical, demographic and serological variables on NN, NA and anti-nuc levels were assessed by univariable and multivariable analysis.

Results: Patients with SLE had higher mean NN than healthy controls or patients with other autoimmune rheumatic diseases (P =0.01). Serum samples from 18 out of 49 (36.7%) of SLE patients were never positive for NN. This group of 18 patients was characterized by lower anti-double stranded DNA antibodies (anti-dsDNA), disease activity and use of immunosuppressants. In the remaining 63.3%, NN levels were variable. High NN was significantly associated with anti-Sm antibodies, vasculitis, immunosuppressants, hydroxychloroquine and age at diagnosis. NN levels were raised in neuropsychiatric flares. NN levels did not completely parallel NA results, thus providing additional information over measuring nitration status alone. NN levels were not associated with anti-nuc levels.

Conclusions: NN are raised in a subset of patients with SLE, particularly those who are anti-Sm positive. Elevated NN may be a marker of vascular activation and neuropsychiatric flares in these patients.

PubMed Disclaimer

Figures

Figure 1
Figure 1
NN levels in patients with SLE compared to healthy and autoimmune disease controls. This figure shows the results obtained in the NN ELISA on testing serum samples from patients with SLE in comparison with healthy controls and patients with other autoimmune rheumatic diseases (myositis, rheumatoid arthritis and Sjogren’s syndrome). NN levels were higher in the SLE group than the other groups (P = 0.01 by one way ANOVA/Kruskal Wallis test). NN, nitrated nucleosomes; SLE, systemic lupus erythematosus.
Figure 2
Figure 2
Variation of NN and anti-dsDNA levels and global BILAG scores over time. This figure shows the variation of serum NN levels over time in five patients compared to anti-dsDNA levels (A-E) and global BILAG scores (F-J). anti-dsDNA, anti-double stranded DNA antibodies; BILAG, British Isles Lupus Assessment Group; NN, nitrated nucleosomes.
See this image and copyright information in PMC

References

    1. Manzi S, Meilahn EN, Rairie JE, Conte CG, Medsger TA Jr, Jansen-McWilliams L, D’Agostino RB, Kuller LH. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study. Am J Epidemiol. 1997;16:408–415. doi: 10.1093/oxfordjournals.aje.a009122. - DOI - PubMed
    1. Roman MJ, Shanker BA, Davis A, Lockshin MD, Sammaritano L, Simantov R, Crow MK, Schwartz JE, Paget SA, Devereux RB, Salmon JE. Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus. N Engl J Med. 2003;16:2399–2406. doi: 10.1056/NEJMoa035471. - DOI - PubMed
    1. Bruce IN. ‘Not only…but also’: factors that contribute to accelerated atherosclerosis and premature coronary heart disease in systemic lupus erythematosus. Rheumatology (Oxford) 2005;16:1492–1502. doi: 10.1093/rheumatology/kei142. - DOI - PubMed
    1. Belmont HM, Levartovsky D, Goel A, Amin A, Giorno R, Rediske J, Skovron ML, Abramson SB. Increased nitric oxide production accompanied by the up-regulation of inducible nitric oxide synthase in vascular endothelium from patients with systemic lupus erythematosus. Arthritis Rheum. 1997;16:1810–1816. doi: 10.1002/art.1780401013. - DOI - PubMed
    1. Oates JC, Christensen EF, Reilly CM, Self SE, Gilkeson GS. Prospective measure of serum 3-nitrotyrosine levels in systemic lupus erythematosus: correlation with disease activity. Proc Assoc Am Physicians. 1999;16:611–621. doi: 10.1046/j.1525-1381.1999.99110.x. - DOI - PubMed

Publication types

LinkOut - more resources