Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study

• Type of Material: Article
• Authors: Isabel Ferreira, University College London; Sara Croca, University College London; Maria Gabriella Raimondo, University College London; Manjit Matharu, Institute of Neurology and The National Hospital for Neurology and Neurosurgery; Sarah Miller, Institute of Neurology and The National Hospital for Neurology and Neurosurgery; Ian Giles, University College London; David Isenberg, University College London; Yiannis Ioannou, University College London; John G. Hanly, Dalhousie University; Murray B. Urowitz, University of Toronto; Nicole Anderson, University of Toronto; Cynthia Aranow, Feinstein Institute for Medical Research; Anca Askanase, Columbia University; Sang-Cheol Bae, Hanyang University; Sasha Bernatsky, McGill University; Ian N. Bruce, University of Manchester; Jill Buyon, New York School of Medicine; Ann E. Clarke, University of Calgary; Mary Ann Dooley, University of North Carolina; Paul Fortin, Centre Hospitalier de l’Université Laval (CHUL); Ellen Ginzler, Downstate Medical Center Rheumatology; Dafna Gladman, University of Toronto; Caroline Gordon, University of Birmingham; Murat Inanc, Istanbul University; Søren Jacobsen, Rigshospitalet; Kenneth Kalunian, University of California San Diego; Diane Kamen, Medical University of South Carolina; Munther Khamashta, Kings College London; S Sam Lim, Emory University; Susan Manzi, Allegheny Health Network; Joan Merrill, Oklahoma Medical Research Foundation; Ola Nived, Lund University; Christine Peschken, University of Manitoba; Michelle Petri, Johns Hopkins University; Rosalind Ramsey-Goldman, Northwestern University; Guillermo Ruiz-Irastorza, University of Basque Country; Jorje Sanchez-Guerrero, University of Toronto; Kristjan Steinson, Landspitali University Hospital; Gunnar K. Sturfelt, Oklahoma Medical Research Foundation; Ronald van Vollenhoven, Karolinska University Hospital; Daniel J. Wallace, University of California Los Angeles; Asad Zoma, Hairmyres Hospital; Anisur Rahman, University College London
• Language: English
• Date: 2017-12-22
• Publisher: BioMed Central
• Publication Version: Final Published Version
• Copyright Statement: © 2017 The Author(s).
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1186/s13075-017-1495-6
• Title of Journal or Parent Work: Arthritis Research and Therapy
• ISSN: 1478-6354
• Volume: 19
• Issue: 1
• Start Page: 287
• End Page: 287
• Grant/Funding Information: Dr. Ruiz-Irastorza is supported by the Department of Education, Universities and Research of the Basque Government.; Dr. Hanly’s work was supported by the Canadian Institutes of Health Research (research grant MOP-86526).; Dr Petri and the Hopkins Lupus Cohort are supported by the National Institutes of Health (NIH) (grant AR43727).; Drs Ioannou and Isenberg are also supported by Arthritis Research UK Grant 20164.; Dr. Soren Jacobsen is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990).; The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research.; Dr. Clarke holds The Arthritis Society Chair in Rheumatic Diseases at the University of Calgary.; Dr. Sang-Cheol Bae’s work was in part by unrestricted grant (Hanyang University 201600000001387).; Dr. Caroline Gordon’s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals National Health Service (NHS) Trust and the NIHR/Wellcome Trust Clinical Research Facility in Birmingham.; This work was funded by LUPUS UK, The Rosetrees Trust and Arthritis Research UK Programme Grant 19423, and was supported by the National Institute for Health Research (NIHR) University College London Hospitals Biomedical Research Centre.; Dr. Mary Anne Dooley’s work was supported by the NIH grant RR00046.; Dr. Bruce is an NIHR Senior Investigator and is funded by Arthritis Research UK, the National Institute for Health Research Manchester Biomedical Research Unit and the NIHR/Wellcome Trust Manchester Clinical Research Facility.; Dr. Paul R. Fortin presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval, and part of this work was done while he was still holding a Distinguished Senior Investigator of The Arthritis Society.; Dr. Ramsey-Goldman’s work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098).
• Keywords: Life Sciences & Biomedicine; SERUM; PLASMA; BIOMARKERS; HEADACHE; Systemic lupus erythematosus; Rheumatology; Neuropsychiatric; NITRIC-OXIDE SYNTHASE; ANTIBODIES; Nucleosomes; Nitration; Science & Technology; METAANALYSIS; INTERNATIONAL INCEPTION COHORT; DISEASE-ACTIVITY; DIAGNOSIS
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Epidemiology; Health Sciences, Public Health

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.