Neuropsychiatric Events May Be Linked to Nitrated Nucleosome Levels in Lupus

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In some patients with systemic lupus erythematosus, serum levels of nitrated nucleosomes rise at the time of a neuropsychiatric event.
In some patients with systemic lupus erythematosus, serum levels of nitrated nucleosomes rise at the time of a neuropsychiatric event.

Serum levels of nitrated nucleosomes rise at the time of a neuropsychiatric event in some patients with systemic lupus erythematosus (SLE), according to a multicenter, international study published in Arthritis Research & Therapy.1

Previous studies have demonstrated that both nitration and nucleosomes are elevated in association with active SLE.2-6 To determine whether levels of nitrated nucleosomes could be a marker of disease activity in patients with SLE, researchers obtained serum samples from 216 patients with SLE and documented neuropsychiatric events and from 2 matched control patients with SLE but no recorded neuropsychiatric events for each of these patients.1 For the patients with SLE and neuropsychiatric events, samples were taken before, during, and after the event.

Researchers used the same predetermined classification rules for deciding whether the neuropsychiatric event was attributable to SLE that have been used in previous publications.7,8 They found that 26 patients had events attributed to SLE according to the most stringent Systemic Lupus International Collaborative Clinic attribution rule, but there was no association between onset of events and elevated serum nitrated nucleosomes.1 

In 190 patients with neuropsychiatric events not associated with SLE, according to the attribution rules, median serum nitrated nucleosome level was highest at the onset of the event compared with pre- or postevent samples (P =.006). 

Mean serum nitrated nucleosome levels for onset samples were also significantly higher than in the matched controls (P <.001). In these 190 patients, the predominant clinical features were headache, mood disorders, and anxiety.

The authors concluded that, "In this multi-centre study we found that serum [nitrated nucleosome] levels rise at the time of [a neuropsychiatric] event in a proportion of patients with SLE, including some cases of headache. Further studies are needed to determine the value of serum [nitrated nucleosomes] as a biomarker for [neuropsychiatric] SLE."

References

  1. Ferreira I, Croca S, Raimondo MG, et al. Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study [published online December 22, 2017]. Arthritis Res Ther. doi:10.1186/s13075-017-1495-6
  2. Amoura Z, Piette JC, Chabre H, et al. Circulating plasma levels of nucleosomes in patients with systemic lupus erythematosus: correlation with serum antinucleosome antibody titers and absence of clear association with disease activity. Arthritis Rheum. 1997;40(12):2217-2225.
  3. Manson JJ, Ma A, Rogers P, et al. Relationship between anti-dsDNA, anti-nucleosome and anti-alpha-actinin antibodies and markers of renal disease in patients with lupus nephritis: a prospective longitudinal study. Arthritis Res Ther. 2009;11(5):R154. doi: 10.1186/ar2831
  4. Williams Jr RC, Malone CC, Meyers C, Decker P, Muller S. Detection of nucleosome particles in serum and plasma from patients with systemic lupus erythematosus using monoclonal antibody 4H7. J Rheumatol. 2001;28(1):81-94.
  5. Belmont HM, Levartovsky D, Goel A, et al. 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;40(10):1810-1816.
  6. 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;111(6):611-621.
  7. Hanly JG, Urowitz MB, Su L, et al. Prospective analysis of neuropsychiatric events in an international disease inception cohort of patients with systemic lupus erythematosus. Ann Rheum Dis. 2010;69(3):529-535.
  8. Hanly JG, Urowitz MB, Sanchez-Guerrero J, et al. Neuropsychiatric events at the time of diagnosis of systemic lupus erythematosus: an international inception cohort study. Arthritis Rheum. 2007;56(1):265-273.
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