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

Springer Science and Business Media LLC - Tập 19 - Trang 1-9 - 2017
Isabel Ferreira1, Sara Croca1, Maria Gabriella Raimondo1, Manjit Matharu2, Sarah Miller2, Ian Giles1, David Isenberg1,3, Yiannis Ioannou1,3, John G. Hanly4, Murray B. Urowitz5, Nicole Anderson5, Cynthia Aranow6, Anca Askanase7, Sang-Cheol Bae8, Sasha Bernatsky9, Ian N. Bruce10, Jill Buyon11, Ann E. Clarke12, Mary Anne Dooley13, Paul Fortin14, Ellen Ginzler15, Dafna Gladman5, Caroline Gordon16, Murat Inanc17, Søren Jacobsen18, Kenneth Kalunian19, Diane Kamen20, Munther Khamashta21, Sam Lim22, Susan Manzi23, Joan Merrill24, Ola Nived25, Christine Peschken26, Michelle Petri27, Rosalind Ramsey-Goldman28, Guillermo Ruiz-Irastorza29, Jorge Sanchez-Guerrero30, Kristjan Steinson31, Gunnar K. Sturfelt25, Ronald van Vollenhoven32, Daniel J. Wallace33, Asad Zoma34, Anisur Rahman1
1Centre for Rheumatology Research, University College London, Fourth Floor Rayne Institute, London, UK
2Headache Group, Institute of Neurology and The National Hospital for Neurology and Neurosurgery, London, UK
3Arthritis Research UK Centre for Adolescent Rheumatology, UCL/UCLH/Great Ormond Street Hospital, London, UK
4Division of Rheumatology, Dalhousie University and Queen Elizabeth II Health Sciences Center, Halifax, Canada
5Lupus Program, Centre for Prognosis Studies in The Rheumatic Disease and Krembil Research Institute, Toronto Western Hospital, University of Toronto, Toronto, Canada
6Feinstein Institute for Medical Research, Manhasset, USA
7Rheumatology, Columbia University, New York, USA
8Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea
9Divisions of Clinical Epidemiology and Rheumatology, McGill University Health Centre, Montreal, Canada
10Arthritis 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
11New York School of Medicine, New York, USA
12Division of Rheumatology, Cumming School of Medicine, University of Calgary, Calgary, Canada
13Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, USA
14Centre Hospitalier de l’Université Laval (CHUL), Québec, Canada.
15Downstate Medical Center Rheumatology, New York, USA
16Rheumatology Research Group, Institute of Inflammation and Ageing, College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK
17Department of Internal Medicine, Istanbul University, Istanbul, Turkey
18Copenhagen Lupus and Vasculitis Clinic, Centre For Rheumatology and Spine Diseases, Copenhagen, Denmark
19University of California, San Diego, La Jolla, USA
20Division of Rheumatology and Immunology, Medical University of South Carolina, Charleston, USA
21FRCP Division of Women’s Health, King’s College, London, UK
22Department of Medicine, Emory University, Atlanta, USA.
23Allegheny Health Network, Pittsburgh, USA
24Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, USA
25Department of Rheumatology, Lund University, Lund, Sweden
26Department of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, Canada
27Johns Hopkins University School of Medicine, Baltimore, USA
28Northwestern University Feinberg School of Medicine, Chicago, USA
29Autoimmune Diseases Research Unit, Department of Internal Medicine, BioCruces Health Research Institute. Hospital Universitario Cruces, University of the Basque Country, Barakaldo, Spain
30Mount Sinai Hospital and University Health Network, University of Toronto, Toronto, Canada
31Department of Rheumatology, Landspitali University Hospital, Reykjavik, Iceland
32Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Sweden
33Cedars-Sinai Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, USA
34Department of Rheumatology Hairmyres Hospital, East Kilbride, Scotland, UK

Tóm tắt

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. 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. 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. 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.

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