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

Department of Clinical Medicine

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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
Article number	287
Journal	Arthritis Research & Therapy
Volume	19
Number of pages	9
ISSN	1478-6354
DOIs	https://doi.org/10.1186/s13075-017-1495-6
Publication status	Published - 22 Dec 2017

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Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus; a multi-center retrospective case-control studyFinal published version, 563 KBLicence: CC BY

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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 & Therapy, 19, [287]. https://doi.org/10.1186/s13075-017-1495-6

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, S-C, 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 & Therapy, vol. 19, 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.",

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 Sang-Cheol Bae 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",

year = "2017",

month = dec,

day = "22",

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

language = "English",

volume = "19",

journal = "Arthritis Research & Therapy",

issn = "1478-6354",

publisher = "BioMed Central",

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TY - JOUR

T1 - Nitrated nucleosome levels and neuropsychiatric events in systemic lupus erythematosus;

T2 - 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.

U2 - 10.1186/s13075-017-1495-6

DO - 10.1186/s13075-017-1495-6

M3 - Journal article

C2 - 29273092

SN - 1478-6354

VL - 19

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

M1 - 287

ER -

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

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