Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder

Mader, Simone; Jeganathan, Venkatesh; Arinuma, Yoshiyuki; Fujieda, Yuichiro; Dujmović, Irena; Drulović, Jelena; Shimizu, Yasuhiko; Sakuma, Yu; Stern, Joel N. H.; Aranow, Cynthia; Mackay, Meggan; Yasuda, Shinsuke; Atsumi, Tatsuya; Hirohata, Shunsei; Diamond, Betty

doi:10.1002/art.40356

Cited by 56 publications

(50 citation statements)

References 39 publications

(57 reference statements)

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“…A recent study investigated the frequency of autoantibodies classically associated with neuropsychiatric SLE (NPSLE), like ANA and anti-dsDNA, in patients with NMOSD [ 31 ]. Eighty-eight percent of patients with coexisting NMOSD had AQP4-IgG in the serum, whereas AQP4-IgG was only present in the serum of three percent of patients with NPSLE alone.…”

Section: Discussionmentioning

confidence: 99%

“…Eighty-eight percent of patients with coexisting NMOSD had AQP4-IgG in the serum, whereas AQP4-IgG was only present in the serum of three percent of patients with NPSLE alone. In addition, no AQP4-IgG's were found in SLE patients without neuropsychiatric symptoms [ 31 ]. MOG-IgG antibodies were only detected in patients with NMOSD who were negative for AQP4-IgG.…”

Section: Discussionmentioning

confidence: 99%

“…The authors concluded that patients with demyelinating NPSLE should be tested for AQP4-IgG and MOG-IgG in order to help identify comorbid SLE and NMOSD. AQP4-IgG can be considered diagnostic for NMOSD, while none of the other antibodies were diagnostic of demyelinating NPSLE [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

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Lupus and NMOSD: The Blending of Humoral Autoimmunity

Ochi

Shapiro

Melamed

2020

Case Reports in Rheumatology

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Systemic lupus erythematous (SLE) is a chronic autoimmune disease that can target any organ of the body. It may coexist with other autoimmune neurologic conditions such as neuromyelitis optica spectrum disorder (NMOSD). NMOSD, previously known as Devic’s disease, is an autoimmune inflammatory disorder of the central nervous system (CNS) that targets the spinal cord, optic nerves, and certain brain regions. Most current evidence suggests that NMOSD is best described as a CNS astrocytopathy. While these diseases share several immunosuppressive treatment options, timely diagnosis of NMOSD is critical as patients may benefit from treatment tailored specifically to NMOSD as opposed to SLE. Steroids, plasmapheresis, intravenous immunoglobulin, cyclophosphamide, azathioprine, mycophenolate mofetil, and rituximab are used to treat both SLE and NMOSD. However, there are several new therapies (inebilizumab, eculizumab, and satralizumab) recently approved specifically for use in NMOSD. In this case series, we report on three patients with coexisting SLE and NMOSD. We describe a 31-year-old woman who suffered an NMOSD flare after 11 years of clinical remission in the context of receiving an influenza vaccination; her SLE remained quiescent on hydroxychloroquine. Next, we describe a 52-year-old woman with emergence of neurologically devastating seropositive NMOSD in the setting of active treatment for SLE with intravenous cyclophosphamide, oral steroids, and hydroxychloroquine. Last, we describe a 48-year-old woman with emergence of seronegative NMOSD in the setting of SLE that was well-controlled on azathioprine and hydroxychloroquine. These cases illustrate the importance of accurate diagnosis and targeted treatment of NMOSD when coexisting with SLE.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Lupus and NMOSD: The Blending of Humoral Autoimmunity

Ochi

Shapiro

Melamed

2020

Case Reports in Rheumatology

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“…Anti-DNA/NR2 levels in PSNP-SLE were similar with de novo NPSLE, indicating that PSNP-SLE shares some of the clinical features of NPSLE as we suggested in the previous report (10). Mader et al reported the titers of anti-DNA/NR2 antibodies in NPSLE and SLE without NP manifestations (19), indicating that high titer of anti-DNA/NR2 antibodies may be predictive of NPSLE developing.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance of anti‐DNA/N‐methyl‐D‐aspartate receptor 2 antibodies in de novo and post‐steroid cases with neuropsychiatric systemic lupus erythematosus

et al. 2018

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Background: Anti-DNA/ N-methyl-D-aspartate receptor 2 (NR2) antibodies (anti-DNA/NR2 antibodies) are a subset of anti DNA autoantibodies that cross-react with the extracellular domain of the GluN2A/GluN2B subunits of NR2. These antibodies induce apoptosis of hippocampus neurons and psychiatric disorder in mice and humans. Neuropsychiatric SLE (NPSLE) can develop after initiation of corticosteroids (post-steroid neuropsychiatric manifestation: PSNP) or before treatment (de novo NPSLE), however, pathophysiological differences between these subtypes remain unclear. The objective of this study was to clarify the prevalence of anti-DNA/NR2 antibodies in patients with NPSLE. Methods: This study involved a cohort of 4 patients with NPSLE admitted to our hospital. NPSLE patients were classified into two groups, de novo NPSLE and PSNP-SLE. Serum anti-DNA antibodies and anti-DNA/NR2 antibodies were measured by ELISAs. Results: Serum samples were obtained from 24 patients with de novo NPSLE, 25 with PSNP-SLE and 76 healthy controls (HC). The level of anti-DNA/NR2 antibodies in patients with de novo NPSLE and PSNP-SLE were also higher than those in HC. Positive correlation between anti-DNA antibodies and anti-DNA/NR2 antibodies were found in PSNP-SLE, but not significant in de novo NPSLE. Conclusion: The levels of anti-DNA/NR2 antibodies in PSNP-SLE were similar to those in de novo NPSLE. Anti-DNA/NR2 antibodies in PSNP-SLE were suggested as dominant subset of anti-DNA antibodies, indicating that anti-DNA/NR2 antibodies may be a predictive factor in PSNP-SLE.

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“…Of note, it was demonstrated that a subset of murine anti-DNA antibodies cross-reacted with a sequence within the N-methyl-D-aspartate (NMDA) receptor subunit NR2 5 6. More importantly, recent studies have demonstrated that CSF anti-NMDA receptor NR2 antibodies (anti-NR2) are associated with diffuse psychiatric/neuropsychological syndromes of human NPSLE 7–9…”

Section: Introductionmentioning

confidence: 99%

Differential expression of antibodies to NMDA receptor in anti-NMDA receptor encephalitis and in neuropsychiatric systemic lupus erythematosus

Hirohata

Tanaka

2019

Lupus Sci Med

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ObjectiveAnti-NMDA receptor encephalitis is the most prevalent autoimmune encephalitis having characteristic clinical features with autoantibodies against tetrameric transmembrane channels composed of combinations of NR1 subunits of NMDA receptors with NR2 subunits, which are detected by cell-based assay (anti-NR1/NR2). On the other hand, antibodies against the linear epitope in NR2 subunit (anti-NR2) have been shown to be expressed in patients with diffuse psychiatric/neuropsychological syndromes of neuropsychiatric SLE (diffuse NPSLE). However, it has not been explored whether anti-NR1/NR2 might be detected in NPSLE, nor has it been clear whether anti-NR2 might have cross-reactivity with anti-NR1/NR2. The current study was therefore performed to explore the prevalence of anti-NR1/NR2 in NPSLE.MethodsSerum specimens were obtained from 31 patients with NPSLE (22 with diffuse NPSLE and 9 with neurological syndromes or polyneuropathy) and from 18 normal healthy subjects. Anti-NR2 and anti-NR1/NR2 were measured by ELISA and cell-based assay, respectively. The positivity for anti-NR2 was defined by a value exceeding mean+2 SD of normal healthy subjects.ResultsAnti-NR2 was positive in the sera of 19 of 31 patients with NPSLE (in 15 of 22 patients with diffuse NPSLE). By contrast, anti-NR1/NR2 was positive only in 2 of 31 patients with NPSLE (in 2 of 22 patients with diffuse SLE). The positivity for anti-NR1/NR2 was not correlated with anti-NR2 values.ConclusionsThese results demonstrate that the prevalence of anti-NR1/NR2 is extremely low in NPSLE. Moreover, the data also confirm that anti-NR2 antibodies do not have cross-reactivity with anti-NR1/NR2.

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Understanding the Antibody Repertoire in Neuropsychiatric Systemic Lupus Erythematosus and Neuromyelitis Optica Spectrum Disorder

Cited by 56 publications

References 39 publications

Lupus and NMOSD: The Blending of Humoral Autoimmunity

Lupus and NMOSD: The Blending of Humoral Autoimmunity

Clinical significance of anti‐DNA/N‐methyl‐D‐aspartate receptor 2 antibodies in de novo and post‐steroid cases with neuropsychiatric systemic lupus erythematosus

Differential expression of antibodies to NMDA receptor in anti-NMDA receptor encephalitis and in neuropsychiatric systemic lupus erythematosus

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