Neuropsychiatric Lupus Research Articles

Anifrolumab (Saphnelo)


 CADTH recommends that Saphnelo be reimbursed by public drug plans in addition to standard therapy for the treatment of adult patients with active, autoantibody positive, systemic lupus erythematosus (SLE).
 Saphnelo should only be covered to treat adult patients with moderate-severe SLE whose disease cannot be controlled with an oral corticosteroids (OCS) dose of at least 10 mg per day of prednisone or its equivalent in addition to standard of care. Saphnelo should not be covered to treat patients with active severe SLE nephritis or patients with severe or unstable neuropsychiatric SLE.
 Saphnelo should only be reimbursed if prescribed by a physician with expertise in diagnosing and managing SLE and if the cost of Saphnelo is reduced. Saphnelo should not be covered when used in combination with other biologic treatments. After 12 months of treatment, Saphnelo can be prescribed again for patients who show a reduction in disease activity and reduction in glucocorticoid intake compared to when they first started treatment.

Cortical thickness and diffusion tensor imaging in patients with neuropsychiatric systemic lupus erythematosus, with normal structure on brain MRI.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with adverse outcomes; however, imaging abnormalities are only detectable by conventional brain magnetic resonance imaging (MRI) in up to 50% of patients. This study investigated the variability in cortical thickness and diffusion tensor imaging (DTI) parameters among patients with NPSLE whose brain morphology appeared normal on conventional MRI. This retrospective study enrolled 27 female patients with NPSLE (median age: 41.0 years, range: 22-63years) and 34 female healthy controls (median age: 37.0years, range: 24-55years). None exhibited evident abnormalities on conventional MRI. Regional volumes, cortical thickness, and DTI parameters, including fractional anisotropy (FA) and mean diffusivity (MD), were compared. Age-adjusted multivariable logistic regression analysis was conducted to detect significant NPSLE-associated differences. No significant differences in grey or white matter volume fractions were observed between the groups. However, the NPSLE group demonstrated significant cortical thinning in the right pars opercularis (2.45 vs 2.52mm, p = 0.007), reduced FA values in the fornix (0.35 vs 0.40, p = 0.001) and left anterior limb of internal capsule (0.50 vs 0.52, p = 0.012), and increased MD in the fornix (1.71 vs 1.48, p = 0.009) and left posterior corona radiata (0.80 vs 0.76, p = 0.005) compared with those of healthy controls. Cortical thickness measurements and DTI analyses can be used to detect differential variations in patients with NPSLE who exhibit an otherwise normal brain structure on conventional MRI, indicating the existence of subtle changes despite the absence of obvious macrostructural central nervous system involvement of lupus.

Clinical outcome in patients with suspected inflammatory neuropsychiatric lupus treated with immunosuppression: an observational cohort study

BackgroundThe short-term and long-term outcome of inflammatory neuropsychiatric SLE (NPSLE) with immunosuppressive treatment is largely unknown. We used clinical data from our tertiary referral centre for NPSLE to investigate the...

Treatment with lysophosphatidic acid prevents microglial activation and depression-like behaviours in a murine model of neuropsychiatric systemic lupus erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is an incurable disease characterised by neuropsychiatric symptoms, particularly depression. Novel therapeutic options for NPSLE are urgently needed. Several previous reports have suggested that both microglial activation and impaired neurogenesis may be involved in the progression of depression. In contrast, the administration of lysophosphatidic acid (LPA) ameliorates depression and anxiety. Therefore, in the present study, we determined whether treatment with LPA affects microglial activation, impaired neurogenesis, and abnormal behaviour in MRL/lpr mice. In both tail suspension test and forced swim test, the MRL/lpr mice exhibited a significant increase in total immobility time compared with MRL/+ mice. Treatment with LPA significantly suppressed the prolonged immobility time in MRL/lpr mice. In contrast, pretreatment with ki16425 (a specific antagonist of LPA receptor 1 and 3) significantly reversed the effects of LPA. Furthermore, MRL/lpr mice exhibited impairments in spatial working memory and visual cognitive memory, which were suppressed by LPA treatment. The expression levels of TMEM119, CD68, GFAP, and caspase-3 in the hippocampus and prefrontal cortex of MRL/lpr mice were significantly higher than those in MRL/+ mice. Treatment with LPA inhibited these increases in MRL/lpr mice. Pretreatment with ki16425 reversed LPA-mediated inhibition of microglial activation. The quantity of sodium fluorescein that leaked into the brain tissues in MRL/lpr mice were significantly higher than that in MRL/+ mice. Treatment with LPA tended to decrease the sodium fluorescein leakage. These findings suggest that treatment with LPA may regulate microglial activation, which is important in the pathogenesis of NPSLE, as well as blood-brain-barrier weakening and abnormal behaviour.

Inhibitor of NF-κB Kinase Subunit ε Contributes to Neuropsychiatric Manifestations in Lupus-Prone Mice Through Microglial Activation.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by multiorgan dysfunction. Neuropsychiatric SLE (NPSLE) occurs in 30-40% of lupus patients and is the most severe presentation of SLE, frequently resulting in limitation of daily life. Recent studies have shown that microglia, tissue-resident macrophages in the central nervous system, are involved in the pathogenesis of NPSLE. This study was undertaken to explore new therapeutic targets for NPSLE focusing on microglia. RNA sequencing of microglia in MRL/lpr, lupus-prone mice, as well as that of microglia cultured in vitro with cytokines were performed. A candidate gene, which could be a therapeutic target for NPSLE, was identified, and its role in microglial activation and phagocytosis was investigated using specific inhibitors and small interfering RNA. The effect of intracerebroventricular administration of the inhibitor on the behavioral abnormalities of MRL/lpr was also evaluated. Transcriptome analysis revealed the up-regulation of Ikbke, which encodes the inhibitor of NF-κB kinase subunit ɛ (IKBKε) in both microglia from MRL/lpr mice and cytokine-stimulated microglia in vitro. Intracerebroventricular administration of an IKBKε inhibitor ameliorated cognitive function and suppressed microglial activation in MRL/lpr mice. Mechanistically, IKBKε inhibition reduced glycolysis, which dampened microglial activation and phagocytosis. These findings suggest that IKBKε plays a vital role in the pathogenesis of NPSLE via microglial activation, and it could serve as a therapeutic target for NPSLE.

Neuropsihijatrijski lupus - dva lica jedne bolesti (prikaz dva slučaja)

Introduction: Neuropsychiatric lupus (neuropsychiatric systemic lupus erythematosus - NPSLE) is a form of a systemic autoimmune disease - systemic lupus erythematosus (SLE), with dominant central and peripheral nervous system involvement. Nuclear magnetic resonance imaging (NMRI) of the brain is considered the gold standard for diagnosing patients with NPSLE. Treatment of NPSLE includes the following: high doses of corticosteroids, methylprednisolone pulse therapy, intravenous immunoglobulins, plasmapheresis, immunosuppressants (cyclophosphamide, azathioprine, mycophenolate mofetil), and biological therapy - rituximab. Case reports: In this paper, we present two patients diagnosed with neuropsychiatric lupus, with different clinical manifestations of the disease, as well as the diagnostics performed, and the good clinical outcomes of immunosuppressive therapy achieved in both patients. Conclusion: The pathogenesis of NPSLE involves neuroinflammatory (autoimmune) and ischemic mechanisms. Neuroimaging has shown good results in differentiating patients with SLE from controls. The goal of SLE treatment is to achieve remission or low disease activity and to prevent episodes of exacerbation. Treatment with intravenous cyclophosphamide as well as with systemic corticosteroids has shown significantly positive results in patients with NPSLE. There is great need, in the future, for new biomarkers in the serum and cerebrospinal fluid (CSF), as well as for more innovative radiological procedures. Additional clinical trials that would lead to new therapeutic options for the treatment of NPSLE are necessary.

Anti-N-methyl-D-Aspartate Receptor Encephalitis

Background: Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is an auto-immune encephalitis with prominent neuropsychiatric manifestations that may be paraneoplastic. Clinical Description: A teenage girl presented with an acute illness of 4 days with symptoms of generalized weakness of all four limbs, behavioral abnormalities, and a generalized convulsion. On examination, the child was hemodynamically stable and disoriented to time, place, or person. There was the loss of recent memory. The remaining neurological and systemic examination was normal. The differential diagnoses considered were toxic or metabolic encephalopathy, neurological Wilson's disease, acute intermittent porphyria, autoimmune encephalitis, and neuropsychiatric systemic lupus erythematosus. Investigations were planned for the causes that could not be excluded by history, examination, and baseline investigations. Salient reports were normal brain magnetic resonance imaging (MRI), nonspecific electroencephalogram abnormalities, and absence of pleocytosis and biochemical abnormalities but positive anti-NMDAR antibodies in the cerebrospinal fluid. A right adnexal cystic solid mass was identified in the abdominal ultrasound with the radiological appearance of an ovarian teratoma or germ cell tumor on MRI. Alpha-fetoprotein levels were raised. Management: The patient underwent right salpingo-oophorectomy. The histopathological diagnosis was an immature ovarian teratoma. The patient received first-line and then second-line immunotherapy (when there was no response), as well as chemotherapy. Signs of improvement appear after 6 weeks, with complete recovery within 6 months. Conclusion: Pediatric ovarian teratoma-associated anti-NMDAR encephalitis is rare, but neuropsychiatric symptoms should prompt the clinician to think of this diagnosis in girls. Early treatment is associated with a good prognosis.

A case of Neuropsychiatric systemic lupus erythematosus with varying stenotic lesions in several cerebral major arteries and a vertebral artery aneurysm

A 42 years old female suffered from systemic lupus erythematosus (SLE) about 20 years ago. While steroid was tapered for a steroid-induced psychiatric disorder, she presented with an acute confusional state and was diagnosed with neuropsychiatric SLE (NPSLE). MRI showed acute infarction mainly in the cortex of the right temporal lobe and MRA demonstrated dynamic subacute morphological changes such as stenosis and dilation in several major intracrainal arteries. The right vertebral artery diffusely dilated and subsequently formed an aneurysm in a week. Contrast-enhanced MRI vessel-wall imaging showed a remarkable enhancement of the aneurysm wall, which might indicate an unstable unruptured aneurysm. The prompt introduction of intravenous cyclophosphamide improved both clinical and radiological signs. Our case indicates that intensive immunosuppressive treatments should be considered in NPSLE patients with varying vasospasm and aneurysm, indicating exacerbated disease activity.

Abnormal cerebral hemodynamics and blood-brain barrier permeability detected with perfusion MRI in systemic lupus erythematosus patients

ObjectiveDynamic susceptibility contrast (DSC) magnetic resonance imaging (MRI) has previously shown alterations in cerebral perfusion in patients with systemic lupus erythematosus (SLE). However, the results have been inconsistent, in particular regarding neuropsychiatric (NP) SLE. Thus, we investigated perfusion-based measures in different brain regions in SLE patients with and without NP involvement, and additionally, in white matter hyperintensities (WMHs), the most common MRI pathology in SLE patients. Materials and methodsWe included 3 T MRI images (conventional and DSC) from 64 female SLE patients and 19 healthy controls (HC). Three different NPSLE attribution models were used: the Systemic Lupus International Collaborating Clinics (SLICC) A model (13 patients), the SLICC B model (19 patients), and the American College of Rheumatology (ACR) case definitions for NPSLE (38 patients). Normalized cerebral blood flow (CBF), cerebral blood volume (CBV) and mean transit time (MTT) were calculated in 26 manually drawn regions of interest and compared between SLE patients and HC, and between NPSLE and non-NPSLE patients. Additionally, normalized CBF, CBV and MTT, as well as absolute values of the blood-brain barrier leakage parameter (K2) were investigated in WMHs compared to normal appearing white matter (NAWM) in the SLE patients. ResultsAfter correction for multiple comparisons, the most prevalent finding was a bilateral significant decrease in MTT in SLE patients compared to HC in the hypothalamus, putamen, right posterior thalamus and right anterior insula. Significant decreases in SLE compared to HC were also found for CBF in the pons, and for CBV in the bilateral putamen and posterior thalamus. Significant increases were found for CBF in the posterior corpus callosum and for CBV in the anterior corpus callosum. Similar patterns were found for both NPSLE and non-NPSLE patients for all attributional models compared to HC. However, no significant perfusion differences were revealed between NPSLE and non-NPSLE patients regardless of attribution model. The WMHs in SLE patients showed a significant increase in all perfusion-based metrics (CBF, CBV, MTT and K2) compared to NAWM. ConclusionOur study revealed perfusion differences in several brain regions in SLE patients compared to HC, independently of NP involvement. Furthermore, increased K2 in WMHs compared to NAWM may indicate blood-brain barrier dysfunction in SLE patients. We conclude that our results show a robust cerebral perfusion, independent from the different NP attribution models, and provide insight into potential BBB dysfunction and altered vascular properties of WMHs in female SLE patients. Despite SLE being most prevalent in females, a generalization of our conclusions should be avoided, and future studies including all sexes are needed.

Internalization of Anti-DNA Antibodies by Rat Brain Cells: A Possible Pathogenetic Mechanism of Neuropsychiatric Lupus

Accumulating evidence suggests that DNA-anti-DNA antibody immune complexes are endocytosed by immune cells, where they ligate intracellular nucleic acid sensors. This results in production of type I interferon or other cytokines, which may be a significant pathogenetic mechanism in systemic lupus erythematosus (SLE). Most studies thus far have been performed using cell-lines or peripheral blood mononuclear cells, but it remains unclear whether cells from the brain can take up such immune complexes. Because permeability of the blood-brain interfaces is suggested to be increased and autoantibodies are detected in cerebrospinal fluid of SLE patients with neuropsychiatric manifestations, we hypothesize that DNA-anti-DNA immune complexes may be internalized by cells in the central nervous system and cause dysregulation of neural networks. As a first step to test this hypothesis, here we investigated whether anti-DNA antibodies can be internalized by live brain cells in vitro. Primary culture rat astrocytes were incubated for 1 h at 37°C with or without anti-DNA monoclonal antibodies. After washing, fixation, permeabilization and blocking, internalized anti-DNA antibodies were detected by a fluorescent labeled second antibody. We observed that a dsDNA-specific monoclonal antibody entered the nucleus, while a monoclonal antibody cross-reactive with phospholipid and DNA entered the cytoplasm. Isotype-matched control IgG did not enter the cells, suggesting that they were viable and the cell membrane and nuclear membrane were intact at that time. When the cells were incubated at 4°C, internalization of the anti-DNA antibodies was almost completely abolished. This suggests that antibody internalization was not by passive transfer but is an energy-dependent process. Given that astrocytes play indispensable roles in maintaining the function of neural networks, these results may provide a novel perspective on the pathogenetic mechanisms of the neuropsychiatric manifestations often presented in SLE.

Recurrent Neuropsychiatric Systemic Lupus Erythematosus Presenting with Primary Central Nervous System Lymphoma

We report the case of a systemic lupus erythematosus (SLE) patient who was diagnosed with lupus cerebritis, vasculitis, Epstein-Barr virus infection, and consequently, lymphoma. The patient presented to the emergency department with dysarthria, dysphagia, left-sided hemiparesis, and hypesthesia. Initial brain magnetic resonance imaging (MRI) revealed multiple high signal intensities in the cortex and subcortex. Intravenous methylprednisolone and immunoglobulin administration did not improve her symptoms. However, intravenous rituximab improved the parenchymal and angiographic abnormalities. One month later, she developed another acute left-sided hypesthesia. Brain MRI revealed multiple rim-enhancing lesions with perilesional edema, different from the previous lesion. Intravenous methylprednisolone and cyclophosphamide did not improve her symptoms, and she was finally diagnosed with primary central nervous system lymphoma after brain biopsy. Neurological symptoms improved after chemotherapy. Since the incidence of primary central nervous lymphoma is relatively high in SLE patients, careful diagnosis and accurate treatment are needed.

Neuropsychiatric Lupus in Singapore: Disease Characteristics and Outcomes

Neuropsychiatric Lupus in Singapore: Disease Characteristics and Outcomes

Cognitive Performance in Patients with Systemic Lupus Erythematosus Using the Ped-ANAM

Computerized batteries have been widely used to investigate cognitive impairment (CI) in patients with SLE. The aim of this study was to evaluate the cognitive performance of patients with SLE in relation to healthy controls using the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) battery. In addition, we aimed to examine differences in Ped-ANAM scores according to age of disease onset, presence of disease activity, and disease damage. We included 201 consecutive adult-onset (aSLE) and childhood-onset SLE (cSLE) patients who were being followed at the hospital's rheumatology outpatient clinic and 177 healthy controls. We applied the percentage of correct answers on the Ped-ANAM subtests and the Performance Validity Index (PVI) metric and correlated them with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus Erythematosus Damage Index (SDI). Then, we established their relationships with neuropsychiatric systemic lupus erythematosus (NPSLE). We observed CI in a total of 38 (18.9%) SLE patients and 8 (4.5%) healthy controls (p < 0.001). CI was observed in eight (19.5%) cSLE patients and 32 (20%) aSLE patients (p = 0.8175). Individual analysis of the aSLE subtests showed a significant difference in all subtests compared to healthy controls; the greatest differences were in matching to sample (p < 0.001) and memory search ( p < 0.001). In the cSLE group, we observed a difference in the code substitution subtests (p = 0.0065) compared to the healthy controls. In the evaluation of clinical outcomes, disease activity was significantly correlated with CI in cSLE (r = 0.33; p = 0.042) and aSLE (r = 0.40; p = 0.001). We also observed an association between disease activity and neuropsychiatric manifestations (p = 0.0012) in aSLE. In conclusion, we determined that cognitive dysfunction, mainly in memory and attention, was more prevalent in patients with SLE. In both the cSLE and aSLE groups, disease activity was associated with worse cognitive function. This is the first study to use the Ped-ANAM in Brazil. Longitudinal studies are necessary to determine how the Ped-ANAM will perform over time.

Small molecule compound K-7174 attenuates neuropsychiatric manifestations in lupus-prone mice

The neuropsychiatric manifestations of systemic lupus erythematosus (NPSLE) present significant morbidity and mortality due to frequent non-response or adverse effects of the current clinical drugs. The disruption of the blood–brain barrier (BBB) contributes to inflammatory NPSLE disease progression. K-7174, a highly piperazine-derived compound, inhibits leukocyte adhesion and inflammatory factor expression. The present study aimed to comprehensively assess the treatment effect of neurobehavioral deficits in MRL/lpr mice, a validated neuropsychiatric lupus model. The intraperitoneal injection of K-7174 alleviated lupus-like symptoms and improved cognitive dysfunction in MRL/lpr mice. Also, it significantly attenuated neuronal degeneration and decreased serum albumin deposition in the hippocampus. Furthermore, K-7174 acted directly on the brain microvascular endothelial bEnd.3 cells and reduced the BBB permeability, manifested by inhibiting the activation of brain microvascular endothelial cells and increasing the expression of tight junctions (TJs). Notably, in vitro experiments showed that K-7174 alleviates the decreased ZO1 and Occludin expression in bEnd.3 cells caused by lactate increase, improving cell permeability via the MCT4/NKAP/CREB signaling pathway. These findings suggested that K-7174 mediates the attenuation of NPSLE in MRL/lpr mice, indicating a promising therapeutic strategy for NPSLE.

A Severe Case of Lupus Cerebritis

Objective Lupus cerebritis is a rare but potentially fatal complication of SLE. Prompt diagnosis and rapid initiation of therapy can prove lifesaving. Background We present the case of a 31-year-old woman who presented to the emergency department with one week of fevers, headaches and confusion. Review of systems was notable for diffuse muscle and joint pains, weakness and a rash. SLE and Sjogren's were both diagnosed six months prior to admission and treatment included prednisone, methotrexate, and hydroxychloroquine. She self-discontinued therapy six weeks prior to seek natural remedies in her native Ecuador. Vitals on admission were 102.2 F, 111 beats/min, 96/67 mmHg, 16 breaths/min and 95% SO2 on 2 L/min via nasal cannula. Physical exam was notable for conjunctival injection, hypopyon (OD), and oral ulcers with visible bleeding. Pelvic exam showed shallow ulcerations of the vaginal mucosa. Neurological exam was significant for diffuse weakness. There were punched-out ulcers on the digits of both hands. Laboratory markers of lupus disease activity were markedly abnormal. An MRI of the brain showed numerous punctate foci of restricted diffusion in the supra and infratentorial brain parenchyma. Few of the lesions showed subtle rim-enhancement and microhemorrhagic foci. CSF analysis showed 220 WBC/mL (70% PMNs), glucose 13 mg/dL and protein 63.7 mg/dL. No CSF oligoclonal bands were detected. CSF/serum albumin index showed mild impairment of the blood brain barrier. Cultures of CSF, blood, urine and sputum showed no growth. Design/Methods NA. Results The patient improved significantly upon initiation of pulsed corticosteroids, plasma exchange, and cyclophosphamide. She was transitioned to steroid-sparing agents and is doing well. Conclusions Lupus cerebritis can be the dominant syndrome in a patient presenting with uncontrolled SLE. Imaging and CSF findings can be dramatic and evoke infectious syndromes. Once alternative diagnoses have been ruled out lupus cerebritis should be managed aggressively to ensure good outcomes.

Pulmonary involvement: A potential independent factor for quality of life in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multi-systemic autoimmune disease. SLE patients may experience a wide range of physical, psychological, and social perception of well-being influenced by the patient illness that are not always fully captured by descriptions of the disease's physiological consequences alone. Nowadays, patients with SLE have a better survival than decades ago, nevertheless still experience a low health related quality of life (HRQoL). Assessing disease activity in SLE is crucial to the physician as it forms the basis for treatment decisions, moreover careful evaluation for respiratory involvement should be routinely considered. More chronic lung disease related to SLE can have a significant negative effect on patient well-being and physical performance status and are detrimental to quality of life. The aim of this study was to evaluate quality of life changes in SLE patients using Lupus QoL scale, assessing their correlation with different disease aspects particularly pulmonary manifestations and predictors for worse QoL. Total of 60 SLE patients, who fulfilled the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria, were enrolled in this study. Disease activity was measured by systemic lupus erythematosus disease activity index (SLEDAI) and quality of life was assessed by Lupus QoL. Pulmonary evaluation included pulmonary function tests parameters (PFTs), mMRC dyspnea scale, HRCT score, and pulmonary damage index. Lupus QoL had a strong significant correlations with PFTs FEV1, FVC, and DLCO (r = 0.79, 0.78, 0.76, p < .001), respectively}, while Lupus QoL had strong negative correlations with both mMRC dyspnea scale and HRCT score (r = -0.96, -0.85, p < .001), respectively, and moderate negative correlation with neuropsychiatric lupus (NPSLE) (r = -0.61, p < .001). Weak negative correlations were found between Lupus QoL, photosensitivity, alopecia, Raynaud's and renal affection (r = -0.29, -0.30, -0.30, 0.38, p = .03, .02, .02, .002), respectively. NPSLE and pulmonary involvement were the most consistent predictors of low HRQoL [contributing 36% and 18% of the variance of Lupus QoL], respectively. Lupus QoL is negatively correlated with different SLE clinical parameters particularly pulmonary manifestations. Neuropsychiatric, pulmonary, renal affection, and SLEDAI are the best determinants for worse Lupus QoL.

Electroconvulsive Therapy Is an Effective Treatment Modality in Children With Lupus Cerebritis With Persistent Catatonia.

A 13-year-old girl with neuropsychiatric systemic lupus erythematosus presenting with psychosis and persistent catatonia unresponsive to immunosuppressive agents and a benzodiazepine was successfully treated with ECT.

Lipidomics Changes in a Murine Model of Neuropsychiatric Lupus.

Neuropsychiatric lupus (NPSLE) is one of the important manifestations of systemic lupus erythematosus. Previous studies mainly focused on the disruption of the blood-brain barrier and the production of brain-reactive autoantibodies, However, there is no comprehensive lipidomic analysis in NPSLE. Therefore, this research evaluated the lipidomic analysis in the hippocampus and liver of NPSLE mice with mood disorders, to explore the influence of the liver-brain axis on this disease. MRL/lpr mice and MRL/mpj mice were respectively used as NPSLE and control groups. Behavioral tests and systemic disease characteristics of mice were assessed at the age of 18 weeks. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) was used for lipid metabolite determination. Multivariate statistical analysis was used to identify lipid metabolites that were differentially expressed in two groups. Our results showed that 355 and 405 lipid metabolites were differentially expressed between the NPSLE and control groups in the hippocampus and liver. According to the pathway enrichment analysis, several pathways were affected, and the glycerophospholipid metabolism pathway was most relevant to the mouse's depressive behavior. Based on UPLC-MS/MS, the results provide evidence for how the liver-brain axis affects NPSLE and improve the understanding of NPSLE pathogenesis.

Relationship Between Cognitive Dysfunction (MoCA-INA Score) with Disease Activity, Erythrocyte Sedimentation Rate, and C-Reactive Protein in Systemic Lupus Erythematosus Patients

BACKGROUND: Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is one of the clinical manifestations affecting the brain in SLE, which the most frequent condition was cognitive dysfunction (CD). CD has a negative impact on the quality of life of SLE patients and causes impaired social function and reduced work productivity. Previous studies regarding correlation between cognitive dysfunction with disease activity, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) showed various results. AIM: The purpose of this study was to assess the correlation of CD using MoCA- INA score with disease activity (SLEDAI-2K score), ESR and CRP in SLE patients. METHODS: A cross-sectional study design was applied in this research. The subjects of this research were SLE patients measured by MoCA-INA score, SLEDAI-2K score, ESR, and CRP. Spearman rank correlation test was applied in this study to assess the relationship of the variables. RESULT: The study subjects consisted of 53 women diagnosed with SLE with an average age of 34 years old. 49.1 % of the subjects had high school education background. There was a moderate significant correlation between MoCA-INA score and ESR (r= -0.408, p=0.002) and also to CRP (r= -0.314 p=0.022). There was no significant correlation of disease activity and MoCA-INA score (r = -0.086 p = 0.539). CONCLUSION: The low levels of ESR and CRP were associated with CD in SLE patients. KEYWORDS: cognitive dysfunction, c-reactive protein, disease activity, erythrocyte sedimentation rate, systemic lupus erythematosus.

Machine Learning for Diagnosis of Systemic Lupus Erythematosus: A Systematic Review and Meta-Analysis.

Application of machine learning (ML) for identification of systemic lupus erythematosus (SLE) has been recently drawing increasing attention, while there is still lack of evidence-based support. Systematic review and meta-analysis are conducted to evaluate its diagnostic accuracy and application prospect. PubMed, Embase, Cochrane Library, and Web of Science libraries are searched, in combination with manual searching and literature retrospection, for studies regarding machine learning for identifying SLE and neuropsychiatric systemic lupus erythematosus (NPSLE). Quality Assessment of Diagnostic Accuracy Studies (QUADA-2) is applied to assess the quality of included studies. Diagnostic accuracy of the SLE model and NPSLE model is assessed using the bivariate fixed-effect model, and the data are pooled. Summary receiver operator characteristic curve (SROC) is plotted, and area under the curve (AUC) is calculated. Eighteen (18) studies are included, in which ten (10) focused on SLE and eight (8) on NPSLE. The AUC of SLE identification is 0.95, the sensitivity is 0.90, the specificity is 0.89, the PLR is 8.4, the NLR is 0.12, and the DOR is 73. AUC of NPSLE identification is 0.89, the sensitivity is 0.83, the specificity is 0.83, the PLR is 5.0, the NLR is 0.20, and the DOR is 25. Machine learning presented remarkable performance in identification of SLE and NPSLE. Based on the convenience for inclusion factor collection and non-invasiveness of detection, machine learning is expected to be widely applied in clinical practice to assist medical decision making.