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

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

doi:10.1186/s13075-017-1495-6

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

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 FortinEllen 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^*

^*Corresponding author for this work

Medicine, Rheumatology Division

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

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.

Original language	English (US)
Article number	287
Journal	Arthritis Research and Therapy
Volume	19
Issue number	1
DOIs	https://doi.org/10.1186/s13075-017-1495-6
State	Published - Dec 22 2017

Funding

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. Drs Ioannou and Isenberg are also supported by Arthritis Research UK Grant 20164. Dr. Hanly’s work was supported by the Canadian Institutes of Health Research (research grant MOP-86526). 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. Dr Petri and the Hopkins Lupus Cohort are supported by the National Institutes of Health (NIH) (grant AR43727). 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. 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. 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. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Dr. Soren Jacobsen is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990). 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). Dr. Mary Anne Dooley’s work was supported by the NIH grant RR00046. Dr. Ruiz-Irastorza is supported by the Department of Education, Universities and Research of the Basque Government. None of these funding bodies played any role in the design of the study, collection, analysis or interpretation of the data.

Keywords

Neuropsychiatric
Nitration
Nucleosomes
Systemic lupus erythematosus

ASJC Scopus subject areas

Rheumatology
Immunology and Allergy
Immunology

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Ferreira, I., Croca, S., Raimondo, M. G., Matharu, M., Miller, S., Giles, I., Isenberg, D., Ioannou, Y., Hanly, J. G., Urowitz, M. B., Anderson, N., Aranow, C., Askanase, A., Bae, S. C., Bernatsky, S., Bruce, I. N., Buyon, J., Clarke, A. E., Dooley, M. A., ... Rahman, A. (2017). Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study. Arthritis Research and Therapy, 19(1), Article 287. https://doi.org/10.1186/s13075-017-1495-6

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

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 = "Neuropsychiatric, Nitration, Nucleosomes, Systemic lupus erythematosus",

author = "Isabel Ferreira and Sara Croca and Raimondo, {Maria Gabriella} and Manjit Matharu and Sarah Miller and Ian Giles and David Isenberg and Yiannis Ioannou and Hanly, {John G.} and Urowitz, {Murray B.} and Nicole Anderson and Cynthia Aranow and Anca Askanase and Bae, {Sang Cheol} and Sasha Bernatsky and Bruce, {Ian N.} and Jill Buyon and Clarke, {Ann E.} and Dooley, {Mary Anne} and Paul Fortin and Ellen Ginzler and Dafna Gladman and Caroline Gordon and Murat Inanc and S{\o}ren Jacobsen and Kenneth Kalunian and Diane Kamen and Munther Khamashta and Sam Lim and Susan Manzi and Joan Merrill and Ola Nived and Christine Peschken and Michelle Petri and Rosalind Ramsey-Goldman and Guillermo Ruiz-Irastorza and Jorge Sanchez-Guerrero and Kristjan Steinson and Sturfelt, {Gunnar K.} and {van Vollenhoven}, Ronald and Wallace, {Daniel J.} and Asad Zoma and Anisur Rahman",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "22",

doi = "10.1186/s13075-017-1495-6",

language = "English (US)",

volume = "19",

journal = "Arthritis Research and Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

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Ferreira, I, Croca, S, Raimondo, MG, Matharu, M, Miller, S, Giles, I, Isenberg, D, Ioannou, Y, Hanly, JG, Urowitz, MB, Anderson, N, Aranow, C, Askanase, A, Bae, SC, Bernatsky, S, Bruce, IN, Buyon, J, Clarke, AE, Dooley, MA, Fortin, P, Ginzler, E, Gladman, D, Gordon, C, Inanc, M, Jacobsen, S, Kalunian, K, Kamen, D, Khamashta, M, Lim, S, Manzi, S, Merrill, J, Nived, O, Peschken, C, Petri, M, Ramsey-Goldman, R, Ruiz-Irastorza, G, Sanchez-Guerrero, J, Steinson, K, Sturfelt, GK, van Vollenhoven, R, Wallace, DJ, Zoma, A & Rahman, A 2017, 'Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study', Arthritis Research and Therapy, vol. 19, no. 1, 287. https://doi.org/10.1186/s13075-017-1495-6

TY - JOUR

T1 - Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control study

AU - Ferreira, Isabel

AU - Croca, Sara

AU - Raimondo, Maria Gabriella

AU - Matharu, Manjit

AU - Miller, Sarah

AU - Giles, Ian

AU - Isenberg, David

AU - Ioannou, Yiannis

AU - Hanly, John G.

AU - Urowitz, Murray B.

AU - Anderson, Nicole

AU - Aranow, Cynthia

AU - Askanase, Anca

AU - Bae, Sang Cheol

AU - Bernatsky, Sasha

AU - Bruce, Ian N.

AU - Buyon, Jill

AU - Clarke, Ann E.

AU - Dooley, Mary Anne

AU - Fortin, Paul

AU - Ginzler, Ellen

AU - Gladman, Dafna

AU - Gordon, Caroline

AU - Inanc, Murat

AU - Jacobsen, Søren

AU - Kalunian, Kenneth

AU - Kamen, Diane

AU - Khamashta, Munther

AU - Lim, Sam

AU - Manzi, Susan

AU - Merrill, Joan

AU - Nived, Ola

AU - Peschken, Christine

AU - Petri, Michelle

AU - Ramsey-Goldman, Rosalind

AU - Ruiz-Irastorza, Guillermo

AU - Sanchez-Guerrero, Jorge

AU - Steinson, Kristjan

AU - Sturfelt, Gunnar K.

AU - van Vollenhoven, Ronald

AU - Wallace, Daniel J.

AU - Zoma, Asad

AU - Rahman, Anisur

PY - 2017/12/22

Y1 - 2017/12/22

N2 - 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.

AB - 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.

KW - Neuropsychiatric

KW - Nitration

KW - Nucleosomes

KW - Systemic lupus erythematosus

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UR - http://www.scopus.com/inward/citedby.url?scp=85038897774&partnerID=8YFLogxK

U2 - 10.1186/s13075-017-1495-6

DO - 10.1186/s13075-017-1495-6

M3 - Article

C2 - 29273092

AN - SCOPUS:85038897774

SN - 1478-6354

VL - 19

JO - Arthritis Research and Therapy

JF - Arthritis Research and Therapy

IS - 1

M1 - 287

ER -

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

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