Dong-Jin Park1, Yukitoshi Takahashi2, Ji-Hyoun Kang1, Yi-Rang Yim1, Ji-Eun Kim1, Jeong-Won Lee1, Kyung-Eun Lee1, Jung-Kil Lee3, Shin-Seok Lee4. 1. Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea. 2. Department of Paediatrics, Shizuoka Institute of Epilepsy and Neurological Disorders, Shizuoka, Japan. 3. Department of Neurosurgery, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea. 4. Department of Rheumatology, Chonnam National University Medical School and Hospital, Gwangju, Republic of Korea. shinseok@chonnam.ac.kr.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
Authors: Fabrizio Gardoni; Jennifer Stanic; Diego Scheggia; Alberto Benussi; Barbara Borroni; Monica Di Luca Journal: Cells Date: 2021-01-05 Impact factor: 6.600