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Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study
Authors:Isabel Ferreira  Sara Croca  Maria Gabriella Raimondo  Manjit Matharu  Sarah Miller  Ian Giles  David Isenberg  Yiannis Ioannou  John G. Hanly  Murray B. Urowitz  Nicole Anderson  Cynthia Aranow  Anca Askanase  Sang-Cheol Bae  Sasha Bernatsky  Ian N. Bruce  Jill Buyon  Ann E. Clarke  Mary Anne Dooley  Paul Fortin  Ellen Ginzler  Dafna Gladman  Caroline Gordon  Murat Inanc  Søren Jacobsen  Kenneth Kalunian  Diane Kamen  Munther Khamashta  Sam Lim  Susan Manzi  Joan Merrill  Ola Nived  Christine Peschken  Michelle Petri  Rosalind Ramsey-Goldman  Guillermo Ruiz-Irastorza  Jorge Sanchez-Guerrero  Kristjan Steinson  Gunnar K. Sturfelt  Ronald van Vollenhoven  Daniel J. Wallace  Asad Zoma  Anisur Rahman
Affiliation:1.Centre for Rheumatology Research,University College London, Fourth Floor Rayne Institute,London,UK;2.Headache Group,Institute of Neurology and The National Hospital for Neurology and Neurosurgery,London,UK;3.Arthritis Research UK Centre for Adolescent Rheumatology,UCL/UCLH/Great Ormond Street Hospital,London,UK;4.Division of Rheumatology,Dalhousie University and Queen Elizabeth II Health Sciences Center,Halifax,Canada;5.Lupus Program,Centre for Prognosis Studies in The Rheumatic Disease and Krembil Research Institute, Toronto Western Hospital, University of Toronto,Toronto,Canada;6.Feinstein Institute for Medical Research,Manhasset,USA;7.Rheumatology,Columbia University,New York,USA;8.Department of Rheumatology,Hanyang University Hospital for Rheumatic Diseases,Seoul,South Korea;9.Divisions of Clinical Epidemiology and Rheumatology,McGill University Health Centre,Montreal,Canada;10.Arthritis Research UK Centre for Epidemiology, Centre for Musculoskeletal Research, The University of Manchester, and NIHR Manchester Musculoskeletal Biomedical Research Unit, Central Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre,Manchester,UK;11.New York School of Medicine,New York,USA;12.Division of Rheumatology, Cumming School of Medicine,University of Calgary,Calgary,Canada;13.Thurston Arthritis Research Center,University of North Carolina,Chapel Hill,USA;14.Centre Hospitalier de l’Université Laval (CHUL),Québec,Canada;15.Downstate Medical Center Rheumatology,New York,USA;16.Rheumatology Research Group,Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham,Birmingham,UK;17.Department of Internal Medicine,Istanbul University,Istanbul,Turkey;18.Copenhagen Lupus and Vasculitis Clinic,Centre For Rheumatology and Spine Diseases,Copenhagen,Denmark;19.University of California,San Diego, La Jolla,USA;20.Division of Rheumatology and Immunology,Medical University of South Carolina,Charleston,USA;21.FRCP Division of Women’s Health, King’s College,London,UK;22.Department of Medicine,Emory University,Atlanta,USA;23.Allegheny Health Network,Pittsburgh,USA;24.Clinical Pharmacology,Oklahoma Medical Research Foundation,Oklahoma City,USA;25.Department of Rheumatology,Lund University,Lund,Sweden;26.Department of Medicine, Rady Faculty of Health Sciences,University of Manitoba,Winnipeg,Canada;27.Johns Hopkins University School of Medicine,Baltimore,USA;28.Northwestern University, Feinberg School of Medicine,Chicago,USA;29.Autoimmune Diseases Research Unit, Department of Internal Medicine,BioCruces Health Research Institute. Hospital Universitario Cruces, University of the Basque Country,Barakaldo,Spain;30.Mount Sinai Hospital and University Health Network, University of Toronto,Toronto,Canada;31.Department of Rheumatology,Landspitali University Hospital,Reykjavik,Iceland;32.Rheumatology Unit, Department of Medicine,Karolinska University Hospital,Solna,Sweden;33.Cedars-Sinai Medical Center/David Geffen School of Medicine at UCLA,Los Angeles,USA;34.Department of Rheumatology Hairmyres Hospital,East Kilbride,Scotland, UK
Abstract:

Background

In patients with systemic lupus erythematosus (SLE) there is no serological test that will reliably distinguish neuropsychiatric (NP) events due to active SLE from those due to other causes. Previously we showed that serum levels of nitrated nucleosomes (NN) were elevated in a small number of patients with NPSLE. Here we measured serum NN in samples from a larger population of patients with SLE and NP events to see whether elevated serum NN could be a marker for NPSLE.

Methods

We obtained serum samples from patients in the Systemic Lupus International Collaborative Clinics (SLICC) inception cohort. This included 216 patients with NP events and two matched controls with SLE but no NP events for each of these patients. For the NP patients we tested samples taken before, during and after the NP event.

Results

Twenty-six patients had events attributed to SLE according to the most stringent SLICC attribution rule. In these patients there was no association between onset of event and elevated serum NN. In 190 patients in whom events were not attributed to SLE by the SLICC rules, median serum NN was elevated at the onset of event (P?=?0.006). The predominant clinical features in this group of 190 patients were headache, mood disorders and anxiety.

Conclusions

Serum NN levels rise at the time of an NP event in a proportion of patients with SLE. Further studies are needed to determine the value of serum NN as a biomarker for NPSLE.
Keywords:
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