Anti-N-methyl-D-aspartate receptor antibodies are associated with fibromyalgia in patients with systemic lupus erythematosus: a case-control study.
OBJECTIVE
The high concordance between systemic lupus erythematosus (SLE) and fibromyalgia (FM) suggests common underlying mechanisms related to pain and distress in both patient groups. Increasing evidence indicates that N-methyl-D-aspartate receptors (NMDARs) play a major role in the induction and maintenance of central sensitisation with chronic pain. In this study, we evaluated the role of anti-NMDAR antibodies in the development of FM in patients with SLE.


METHODS
Sera from 104 patients with SLE, 112 patients with FM, and 110 healthy controls were analysed to detect antibodies to the N-terminus of the 2B subunit of NMDARs (GluN2B). Subjects underwent clinical examination and neuropsychiatric evaluation, and completed a questionnaire regarding FM and neuropsychiatric symptoms.


RESULTS
Of the 104 patients with SLE, 18 (17.3%) had FM. The anti-GluN2B antibody titer was significantly higher in patients with SLE (p<0.001). Among patients with SLE, those with concomitant FM had higher anti-GluN2B antibody titers (p<0.05). The anti-GluN2B antibody titer was associated positively with the tender point count (p=0.016) and the widespread pain index (p=0.005), but not with other symptom measurements. Anti-GluN2B antibody-positive patients with SLE were more likely to have neuropsychiatric systemic lupus erythematosus (NPSLE) and concomitant FM (p<0.05). Multivariate analysis showed that the anti-GluN2B antibody was an independent predictor of concomitant FM and NPSLE.


CONCLUSIONS
To our knowledge, this report is the first to suggest that anti-NMDAR antibodies are associated with the pathogenesis of FM with SLE.
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Dong-Jin
DJ
Park
Department of Paediatrics, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan.
Yukitoshi
Y
Takahashi
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Ji-Hyoun
JH
Kang
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Yi-Rang
YR
Yim
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Ji-Eun
JE
Kim
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Jeong-Won
JW
Lee
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Kyung-Eun
KE
Lee
Department of Neurosurgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea.
Jung-Kil
JK
Lee
Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea. shinseok@chonnam.ac.kr.
Shin-Seok
SS
Lee
D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D016022:Case-Control Studies; D015897:Comorbidity; D005260:Female; D005356:Fibromyalgia / Q000453:epidemiology / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000453:epidemiology / Q000276:immunology*; D020945:Lupus Vasculitis, Central Nervous System / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016194:Receptors, N-Methyl-D-Aspartate / Q000276:immunology*; D055815:Young Adult
D001323:Autoantibodies; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate