Neuropsychiatric Lupus Research Articles

Kikuchi-Fujimoto disease as the initial manifestation of systemic lupus erythematosus complicated with macrophage activation syndrome: two case reports and a review of literature

BackgroundKikuchi-Fujimoto disease (KFD) is a self-limiting and benign disease characterized by cervical lymphadenopathy and fever. Although KFD should be made differentially diagnosed from infectious, autoimmune, and malignant diseases, it sometimes occurs in patients with systemic lupus erythematosus (SLE) and can be complicated with macrophage activation syndrome (MAS). However, it is rare that KFD is the initial manifestation of SLE and to be complicated with MAS.Case presentationA 9.6-year-old girl presented with high-grade fever, double-side cervical lymphadenopathy with mild pain of one week, leukopenia, alopecia, and rash on the cheek. During hospitalization, laboratory investigations showed positive antinuclear antibody (ANA), low complement 3 (C3), and low complement 4 (C4). Imaging investigations showed pleural and pericardial effusion. A 10.3-year-old girl presented with intermittent high-grade fever, double-sided cervical lymphadenopathy with obvious pain of 1-month duration, and discoid lesion on the cheek. During hospitalization, laboratory investigations showed positive ANA, leukopenia, thrombocytopenia, anemia with positive Coombs’ test, low C3, and positive Smith antibodies. Both cases were diagnosed with KFD using lymph node biopsy, simultaneously fulfilling the diagnostic criteria of SLE. Subsequently, the two girls became complicated with MAS, followed by interstitial lung disease and neuropsychiatric lupus, respectively. Both patients benefited from high-dose methylprednisolone pulse therapy combined with intravenous cyclophosphamide.ConclusionsMore attention should be paid to differential diagnosis, especially SLE, in children diagnosed with KFD. In addition, children with SLE who presented with KFD as the initial manifestation seem to have a higher risk of developing MAS and experiencing organ involvement.

Cognitive impairment in the immune-mediated inflammatory diseases compared with age-matched controls: Systematic review and meta-regression

ObjectivesTo compare the magnitude of cognitive impairment against age-expected levels across the immune mediated inflammatory diseases (IMIDs: systemic lupus erythematosus [SLE], rheumatoid arthritis [RA], axial spondyloarthritis [axSpA], psoriatic arthritis [PsA], psoriasis [PsO]). MethodsA pre-defined search strategy was implemented in Medline, Embase and Psychinfo on 29/05/2021. Inclusion criteria were: (i) observational studies of an IMID, (ii) healthy control comparison, (iii) measuring cognitive ability (overall, memory, complex attention/executive function, language/verbal fluency), and (iv) sufficient data for meta-analysis. Standardised mean differences (SMD) in cognitive assessments between IMIDs and controls were pooled using random-effects meta-analysis. IMIDs were compared using meta-regression. ResultsIn total, 65 IMID groups were included (SLE: 39, RA: 19, axSpA: 1, PsA: 2 PsO: 4), comprising 3141 people with IMIDs and 9333 controls. People with IMIDs had impairments in overall cognition (SMD: -0.57 [95% CI -0.70, -0.43]), complex attention/executive function (SMD -0.57 [95% CI -0.69, -0.44]), memory (SMD -0.55 [95% CI -0.68, -0.43]) and language/verbal fluency (SMD -0.51 [95% CI -0.68, -0.34]). People with RA and people with SLE had similar magnitudes of cognitive impairment in relation to age-expected levels. People with neuropsychiatric SLE had larger impairment in overall cognition compared with RA. ConclusionsPeople with IMIDs have moderate impairments across a range of cognitive domains. People with RA and SLE have similar magnitudes of impairment against their respective age-expected levels, calling for greater recognition of cognitive impairment in both conditions. To further understand cognition in the IMIDs, more large-scale, longitudinal studies are needed.

The role of type I IFN in autoimmune and autoinflammatory diseases with CNS involvement.

Type I interferons (IFNs) are major mediators of innate immunity, with well-known antiviral, antiproliferative, and immunomodulatory properties. A growing body of evidence suggests the involvement of type I IFNs in the pathogenesis of central nervous system (CNS) manifestations in the setting of chronic autoimmune and autoinflammatory disorders, while IFN-β has been for years, a well-established therapeutic modality for multiple sclerosis (MS). In the present review, we summarize the current evidence on the mechanisms of type I IFN production by CNS cellular populations as well as its local effects on the CNS. Additionally, the beneficial effects of IFN-β in the pathophysiology of MS are discussed, along with the contributory role of type I IFNs in the pathogenesis of neuropsychiatric lupus erythematosus and type I interferonopathies.

Anti-Ribosomal-P Antibody Association with Neuropsychiatric Lupus in Sudanese Patients Attending Rheumatology Clinic in Omdurman Military Hospital.

To assess and establish the relationship between neuropsychiatric systemic lupus erythematosus (NPSLE) involvement and serological biomarkers like antiribosomal-P antibodies. This is an analytical cross-sectional hospital-based study conducted on patients attending Omdurman Military Hospital from July 2019 to December 2019. A total of 90 patients were enrolled, 30 of whom had NPSLE compared with 60 SLE patients without NPSLE. SLE diagnosis was established based on the revised SLICC criteria (presence of at least 4 criteria) for SLE classification, with neuropsychiatric manifestations defined based on the ACR nomenclature. The immunological examination results have been performed by (ELISA immune-enzymatic method, immunofluorescence, and Western immunoblotting test). SPSS v 21.0 software was utilised for data analysis. NPSLE patients exhibited +ve ANA in 96.7% vs 75% in non-NPSLE (P-value = 0.008), antiribosomal-P antibodies (46.7% vs 20%; P-value = 0.0001), anti-nucleosome antibodies (26.7% vs 5%; P-value = 0.005), and anti-histones antibodies (40% vs 20%; P-value = 0.04). ANA antibodies were significantly associated with neurological manifestations as ANA antibodies were common in epilepsy (n = 9; 91%) and stroke (n = 8; 27.6%) (P-value < 0.001). Neuropsychiatric manifestation of systemic lupus erythematosus exhibits variable clinical manifestations. Neuropsychiatric manifestations of SLE are strongly associated with the anti-ribosomal P antibody presence and can be employed as a powerful diagnostic tool.

Treatment with 1,25-Dihydroxyvitamin D3 Delays Choroid Plexus Infiltration and BCSFB Injury in MRL/lpr Mice Coinciding with Activation of the PPARγ/NF-κB/TNF-α Pathway and Suppression of TGF-β/Smad Signaling.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of systemic lupus erythematosus (SLE) involving the nervous system with high morbidity and mortality. A key hypothesis in NPSLE is that a disrupted barrier allows autoantibodies and immune components of peripheral blood to penetrate into the central nervous system (CNS), resulting in inflammation and damage. The blood cerebrospinal fluid barrier (BCSFB), which consists of the choroid plexus and the hypothalamic tanycytes, has long been regarded as an immunological sanctuary site. 1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] is the active form of vitamin D, which plays multiple roles in inflammation and immunoregulation. In this study, we investigated the possible protective effects of 1,25-dihydroxyvitamin D3 against BCSFB dysfunction in NPSLE in MRL/lpr mice and explored the mechanism by which 1,25-dihydroxyvitamin D3 inhibits the progression of NPSLE. In this study, we found that supplementation with 1,25-dihydroxyvitamin D3 markedly improved serological and immunological indices, delayed inflammatory infiltration, delayed neuronal deformation, and upregulated the expression of brain-derived neurotrophic factor (BDNF) proteins in the brain. Furthermore, 1,25-dihydroxyvitamin D3 downregulated proinflammatory cytokines such as nuclear factor kappa-B (NF-κB) and tumor necrosis factor-α (TNF-α) by activating peroxisome proliferator-activated receptor γ (PPARγ), and it reduced the expression of the TGF-β/Smad signaling pathway. Our findings demonstrate that 1,25-dihydroxyvitamin D3 delayed cell infiltration into the choroid plexus and decreased markers suggestive of cognitive decline in MRL/lpr mice, and the mechanism may be related to protection against BCSFB disruption through activation of the anti-inflammatory PPARγ/NF-κB/TNF-α pathway as well as upregulation of BDNF and inhibition of the TGF-β/Smad signaling pathway. These findings provide a novel direction for the study of NPSLE.

Autoimmune RNA dysregulation and seizures: therapeutic prospects in neuropsychiatric lupus.

Lupus autoimmunity frequently presents with neuropsychiatric manifestations, but underlying etiology remains poorly understood. Human brain cytoplasmic 200 RNA (BC200 RNA) is a translational regulator in neuronal synapto-dendritic domains. Here, we show that a BC200 guanosine-adenosine dendritic transport motif is recognized by autoantibodies from a subset of neuropsychiatric lupus patients. These autoantibodies impact BC200 functionality by quasi irreversibly displacing two RNA transport factors from the guanosine-adenosine transport motif. Such anti-BC autoantibodies, which can gain access to brains of neuropsychiatric lupus patients, give rise to clinical manifestations including seizures. To establish causality, naive mice with a permeabilized blood-brain barrier were injected with anti-BC autoantibodies from lupus patients with seizures. Animals so injected developed seizure susceptibility with high mortality. Seizure activity was entirely precluded when animals were injected with lupus anti-BC autoantibodies together with BC200 decoy autoantigen. Seizures are a common clinical manifestation in neuropsychiatric lupus, and our work identifies anti-BC autoantibody activity as a mechanistic cause. The results demonstrate potential utility of BC200 decoys for autoantibody-specific therapeutic interventions in neuropsychiatric lupus.

Upregulation of microRNA-762 suppresses the expression of GIPC3 in systemic lupus erythematosus and neuropsychiatric systemic lupus erythematosus.

BackgroundSystemic lupus erythematosus (SLE), especially neuropsychiatric SLE (NPSLE), is a complex systemic autoimmune disease, characterized by variable course and multiple organ dysfunction. Our study aimed to identify crucial microRNA (miRNAs) in SLE and NPSLE.MethodsTotally 12 cases of serum specimens were collected from General Hospital of Ningxia Medical University (SLE = 4, NPSLE = 4, control = 4). After miRNA sequencing, differential expression analysis, miRNA target prediction, and miRNA‐messenger RNA (mRNA) regulatory network construction were performed to identify the hub miRNAs. The expression of target gene was determined by quantitative reverse transcription‐polymerase chain reaction and Western blot.ResultsThere were 79 and 59 differentially expressed miRNAs (DEmiRNAs) in NPSLE versus Control, and SLE versus Control, respectively. Among 35 overlapped DEmiRNAs, 5 upregulated miRNAs' (hsa‐miR‐762, hsa‐miR‐4270, hsa‐miR‐3663‐3p, hsa‐miR‐4778‐5p, and hsa‐miR‐4516) target genes were supported by at least six databases. The miRNA‐mRNA network indicated that core miRNA hsa‐miR‐762 regulated 1270 target genes. MiR‐762 was significantly upregulated in SLE and NPSLE, and over expression of miR‐762 significantly suppressed GIPC PDZ domain containing family member 3 (GIPC3) expression in SLE and NPSLE.ConclusionsUpregulation of hub miRNA miR‐762 can suppress the expression of GIPC3 in both SLE and NPSLE samples, which is probably involved in the development of SLE and NPSLE. Meanwhile, along with the development from SLE to NPSLE, miR‐762 exhibits higher expression.

Scrub Typhus-Induced Macrophage Activation Syndrome with Flare of Systemic Lupus Erythematosus: A Rare Case Report

Aims: Infection is a major trigger for both Lupus flare and Macrophage activation syndrome. Scrub typhus infection associated with lupus flare or MAS has been very rarely reported. We report a case of scrub typhus-induced MAS along with a flare of disease activity in a neuropsychiatric lupus patient presenting after discontinuation of medications.&#x0D; Presentation of Case: 13-year-old girl, a known case of neuropsychiatric lupus with lupus nephritis, on immunosuppressant for the last 1 year had stopped all medications for 3 months. She had presented with a fever and altered sensorium. Based on clinical and laboratory investigations, a diagnosis of scrub typhus-induced macrophage activation syndrome with a flare of lupus disease activity was made and the patient was treated with injection doxycycline and glucocorticoids. There was rapid clinical improvement with treatment.&#x0D; Discussion: The case emphasizes the importance of identifying the exact trigger behind the deterioration of a patient with lupus and its therapeutic implications. An infection alone requires antibiotics only, flare without infection requires up titrating immunosuppressants but the presence of life-threatening complications like MAS along with infection requires prompt treatment of both facets simultaneously.&#x0D; Conclusion: Scrub typhus infection should be ruled out apart from other common infections in any patient with lupus flare or MAS.

S1719 Digesting a Differential of Zebras in a Unique Case of Pancreatitis

Introduction: While acute pancreatitis is often gallstone or alcohol related, initial workup usually includes consideration of medications, triglyceride level, malignancy, and autoimmune pancreatitis. There remains however a list of rare causes that is often overlooked and misdiagnosed as idiopathic. This is unfortunate and may delay potentially life-saving therapy. Here, we present a unique case of acute pancreatitis seropositive for lupus and mumps that spiraled into lupus cerebritis. Case Description/Methods: A 42-year old male (PMHx. Hypertension) presented with a 6-week history of abdominal pain, weight loss, fever, parotitis and odynophagia. History was significant for close-contact confinement and negative for alcohol use. He was febrile and tachycardic. US was negative for gallstones. CTA showed acute pancreatitis. Labs were significant for WBC 3.21 (abs lymph 0.29), AST 128/ALT 75. Lipase, TSH, lipid panel, and IgG panel was unremarkable. An extensive viral panel was ordered and positive for mumps IgM. He was aggressively fluid resuscitated and developed clinical improvement throughout the week before an unexpected relapse of his symptoms. Over the next few weeks, he developed erythematous and vasculitic appearing rashes, arthralgias, oral ulcers, pericarditis, and eventually acute encephalopathy that required intubation. Skin biopsy showed leukocytoclastic vasculitis and connective tissue disease panel was positive for anti-dsDNA and ANA. He was started on high-dose pulse steroids for lupus cerebritis with remarkable improvement. Discussion: We present a unique case of lupus-pancreatitis in a patient without any prior history. He was seropositive for mumps, which we ordered due to his history. However, mumps-pancreatitis is rare and usually mild. Interestingly, his clinical deterioration coincided with clinical features and serology consistent with lupus. Lupus can falsely elevate mumps IgM and his pancreatitis was likely from lupus-related vasculitis. Lupus-pancreatitis is uncommon and typically presents during lupus flares. To our knowledge, this is the first report of acute pancreatitis as an initial presentation of lupus cerebritis. Lupus-pancreatitis responds to prompt administration of IV steroids. Unfortunately, our patient’s late lupus presentation delayed immunotherapy. Therefore, we recommend consideration of connective tissue diseases in the autoimmune workup of persistent or relapsing pancreatitis.

Choroid Plexus-Infiltrating T Cells as Drivers of Murine Neuropsychiatric Lupus.

T cells are critical in the pathogenesis of systemic lupus erythematosus (SLE) in that they secrete inflammatory cytokines, help autoantibody production, and form autoreactive memory T cells. Although the contribution of T cells to several forms of organ-mediated damage in SLE has been previously demonstrated, the role of T cells in neuropsychiatric SLE (NPSLE), which involves diffuse central nervous system manifestations and is observed in 20-40% of SLE patients, is not known. Therefore, we conducted this study to evaluate how behavioral deficits are altered after depletion or transfer of T cells, to directly assess the role of T cells in NPSLE. MRL/lpr mice, an NPSLE mouse model, were either systemically depleted of CD4+ T cells or intracerebroventricularly injected with choroid plexus (CP)-infiltrating T cells and subsequently evaluated for alterations in neuropsychiatric manifestations. Our study end points included evaluation of systemic disease and assessment of central nervous system changes. Systemic depletion of CD4+ T cells ameliorated systemic disease and cognitive deficits. Intracerebroventricular injection of CP-infiltrating T cells exacerbated depressive-like behavior and worsened cognition in recipient mice compared with mice who received injection of splenic lupus T cells or phosphate buffered saline. Moreover, we observed enhanced activation in CP-infiltrating T cells when cocultured with brain lysate-pulsed dendritic cells in comparison to the activation levels observed in cocultures with splenic T cells. T cells, and more specifically CP-infiltrating antigen-specific T cells, contributed to the pathogenesis of NPSLE in mice, indicating that, in the development of more targeted treatments for NPSLE, modulation of T cells may represent a potential therapeutic strategy.

Acute Cerebellitis in A Case of Systemic Sclerosis overlap with Systemic Lupus Erythematosus: Image study

Systemic lupus erythematosus, and systemic sclerosis are chronic autoimmune diseases with symptoms with different degrees of severity and mechanisms. Hence, we present a 36-year-old female with a history of systemic lupus erythematosus which was later overlapped with systemic sclerosis. She complained of vertigo over three months before developing poor gait. She was diagnosed with truncal ataxia due to her ataxic gait and abnormal point motions. Based on the magnetic resonance imaging, a final diagnosis of a cute cerebellar dysfunction in systemic lupus erythematosus was made. Cyclophosphamide was initiated with a single dose of 500 mg which continued for at least three more monthly cycles, and the methylprednisolone pulse was adjusted to 500 mg/day for three days. Due to measures taken to avert a renal crisis caused by scleroderma, the methyl prednisolone dose was deemed to be lower than the adjusted amount (1 g). A follow-up magnetic resonance imaging showed regression of the lesions after treatment, the cerebral lesion had shrunken, and corticomedullary lesion had resolved entirely. Cerebral ataxia could be developed in patients with sytemic lupus erythematosus in terms of vasculitis, diffusely infiltrating glioma, acute disseminated encephalomyelitis, and systemic lupus erythematosus itself. One of the uncommon signs of neuropsychiatric systemic lupus erythematosus is ataxia and cerebellar involvement. The prognosis is generally favorable while receiving immunosuppressive therapy.

Pathogenesis and treatment of neuropsychiatric systemic lupus erythematosus: A review

Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease with a complex pathogenesis. Neuropsychiatric systemic lupus erythematosus (NPSLE) is a serious complication of SLE that involves the nervous system and produces neurological or psychiatric symptoms. After decades of research, it is now believed that the diverse clinical manifestations of NPSLE are associated with intricate mechanisms, and that genetic factors, blood-brain barrier dysfunction, vascular lesions, multiple autoimmune antibodies, cytokines, and neuronal cell death may all contribute to the development of NPSLE. The complexity and diversity of NPSLE manifestations and the clinical overlap with other related neurological or psychiatric disorders make its accurate diagnosis difficult and time-consuming. Therefore, in this review, we describe the known pathogenesis and potential causative factors of NPSLE and briefly outline its treatment that may help in the diagnosis and treatment of NPSLE.

Belimumab or anifrolumab for systemic lupus erythematosus? A risk-benefit assessment.

Treatment of systemic lupus erythematosus (SLE) currently employs agents with relatively unselective immunosuppressive properties. However, two target-specific biological drugs have been approved: belimumab (anti-B-cell-activating factor/BAFF) and anifrolumab (anti-interferon alpha receptor-1/IFNAR1). Here, we performed a comparative risk-benefit assessment for both drugs based on the role of BAFF and IFNAR1 in host defense and the pathogenesis of SLE and by considering the available data on safety and efficacy. Due to differences in target expression sites, anti-IFNAR1, but not anti-BAFF, might elicit organ-specific effects, consistent with clinical efficacy data. The IFNAR1 is specifically involved in innate and adaptive antiviral immunity in most cells of the body. Consistent with this observation, the available safety data obtained from patients negatively selected for LN and neuropsychiatric SLE, primary immunodeficiencies, splenectomy and chronic HIV, HBV, HCV infections suggest an increased risk for some viral infections such as varicella zoster and perhaps influenza. In contrast, BAFF is mainly involved in adaptive immune responses in lymphoid tissues, thus anti-BAFF therapy modulates SLE activity and prevents SLE flares without interfering with local innate host defense mechanisms and should only marginally affect immune memory to previous pathogen exposures consistent with the available safety data from SLE patients without chronic HIV, HBV or HCV infections. When using belimumab and anifrolumab, careful patient stratification and specific precautions may minimize risks and maximize beneficial treatment effects for patients with SLE.

Progress in the Pathogenesis and Treatment of Neuropsychiatric Systemic Lupus Erythematosus.

Neuropsychiatric systemic lupus erythematosus (NPSLE) has a broad spectrum of subtypes with diverse severities and prognoses. Ischemic and inflammatory mechanisms, including autoantibodies and cytokine-mediated pathological processes, are key components of the pathogenesis of NPSLE. Additional brain-intrinsic elements (such as the brain barrier and resident microglia) are also important facilitators of NPSLE. An improving understanding of NPSLE may provide further options for managing this disease. The attenuation of neuropsychiatric disease in mouse models demonstrates the potential for novel targeted therapies. Conventional therapeutic algorithms include symptomatic, anti-thrombotic, and immunosuppressive agents that are only supported by observational cohort studies, therefore performing controlled clinical trials to guide further management is essential and urgent. In this review, we aimed to present the latest pathogenetic mechanisms of NPSLE and discuss the progress in its management.

Neuropsychiatric manifestations and their attribution to systemic lupus erythematosus: a retrospective single-center study in a Polish population.

Neuropsychiatric (NP) manifestations occur in patients with systemic lupus erythematosus (SLE), and it is challenging to distinguish these manifestations from other neuropsychiatric conditions. We aimed to assess the prevalence of primary neuropsychiatric SLE (NPSLE) in a Polish cohort of SLE patients. This retrospective, cross‑sectional study evaluated 164 patients with SLE. NP manifestations were attributed to SLE using the Italian model. Demographic and clinical data, including disease activity (measured by the Systemic Lupus Erythematosus Disease Activity Index version 2000 [SLEDAI‑2K] and the Physician Global Assessment) and organ damage (measured by the Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index), were obtained in patients with and without NP manifestations attributed to SLE. The final analysis set included 143 patients, 34 of whom (23.8%) had NP manifestations attributed to SLE. The age of the patients with NPSLE and the age of disease onset were significantly lower in comparison with those without NP symptoms attributed to SLE (median [interquartile range], 38 [29-45] vs 45 [32-55] years; P = 0.009, and 35 [24-38] vs 40 [25-48] years; P = 0.03, respectively). The disease activity and proportion of patients with active disease (SLEDAI‑2K ≥6) was significantly higher in the NPSLE patients than in those without NP symptoms attributed to SLE (P <0.005; 100% vs 85.3%; P = 0.01, respectively). NP manifestations in the central nervous system were the most frequent (91.5%). In the patients with NPSLE, cerebrovascular disease, seizures, cognitive dysfunction, psychosis, and cranial neuropathy occurred most often. NP manifestations occurred mainly in young patients with high disease activity. Cerebrovascular disease, seizures, psychosis, cognitive dysfunction, and cranial neuropathy were the most frequent manifestations of NPSLE.

Insights into the role of neutrophils in neuropsychiatric systemic lupus erythematosus: Current understanding and future directions.

Central nervous system (CNS) involvement of systemic lupus erythematosus (SLE), termed neuropsychiatric SLE (NPSLE), is a major and debilitating manifestation of the disease. While patients with SLE mostly complain of common neuropsychological symptoms such headache and mild mood disorders that may not even be technically attributed to SLE, many SLE patients present with life-threatening NPSLE syndromes such as cerebrovascular disease, seizures and psychosis that are equally challenging in terms of early diagnosis and therapy. While we are just beginning to unravel some mysteries behind the immunologic basis of NPSLE, advancements in the mechanistic understanding of the complex pathogenic processes of NPSLE have been emerging through recent murine and human studies. The pathogenic pathways implicated in NPSLE are multifarious and various immune effectors such as cell-mediated inflammation, autoantibodies and cytokines including type I interferons have been found to act in concert with the disruption of the blood-brain barrier (BBB) and other neurovascular interfaces. Beyond antimicrobial functions, neutrophils are emerging as decision-shapers during innate and adaptive immune responses. Activated neutrophils have been recognized to be involved in ischemic and infective processes in the CNS by releasing neutrophil extracellular traps (NETs), matrix metalloproteinase-9 and proinflammatory cytokines. In the context of NPSLE, these mechanisms contribute to BBB disruption, neuroinflammation and externalization of modified proteins on NETs that serve as autoantigens. Neutrophils that sediment within the peripheral blood mononuclear cell fraction after density centrifugation of blood are generally defined as low-density neutrophils (LDNs) or low-density granulocytes. LDNs are a proinflammatory subset of neutrophils that are increased with SLE disease activity and are primed to undergo NETosis and release cytokines such as interferon-α and tumor necrosis factor. This review discusses the immunopathogenesis of NPSLE with a focus on neutrophils as a core mediator of the disease and potential target for translational research in NPSLE.

Cerebrovascular Accident as a First Manifestation of Neuropsychiatric Systemic Lupus Erythematosus; a Comprehensive Review; a Case Report

Cerebrovascular Accident as a First Manifestation of Neuropsychiatric Systemic Lupus Erythematosus; a Comprehensive Review; a Case Report

Pathogenic neuropsychiatric effect of stress-induced microglial interleukin 12/23 axis in systemic lupus erythematosus

ObjectivesThe central nervous system disorder in systemic lupus erythematosus (SLE), called neuropsychiatric lupus (NPSLE), is one of the most severe phenotypes with various clinical symptoms, including mood disorder, psychosis and...

Noise-Immune Extreme Ensemble Learning for Early Diagnosis of Neuropsychiatric Systemic Lupus Erythematosus.

Early diagnosis is currently the most effective way of saving the life of patients with neuropsychiatric systemic lupus erythematosus (NPSLE). However, it is rather difficult to detect this terrible disease at the early stage, due to the subtle and elusive symptomatic signals. Recent studies show that the 1H-MRS (proton magnetic resonance spectroscopy) imaging technique can capture more information reflecting the early appearance of this disease than conventional magnetic resonance imaging techniques. 1H-MRS data, however, also presents more noises that can bring serious diagnosis bias. We hence proposed a noise-immune extreme ensemble learning technique for effectively leveraging 1H-MRS data for advancing the early diagnosis of NPSLE. Our main results are that 1) by developing generalized maximum correntropy criterion in the kernel extreme learning setting, many types of non-Gaussian noises can be distinguished, and 2) weighted recursive feature elimination, using maximal information coefficient to weight feature's importance, helps to further alleviate the bad impact of noises on the diagnosis performance. The proposed method is assessed on a publicly available dataset with 97.5% accuracy, 95.8% sensitivity and 99.9% specificity, which well demonstrates its efficacy.

Different blood-brain-barrier disruption profiles in multiple sclerosis, neuromyelitis optica spectrum disorders, and neuropsychiatric systemic lupus erythematosus.

To assess differences in BBB damage profiles by measuring serum levels of soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and S100 calcium-binding protein B (S100B) in relapsing-remitting multiple sclerosis (RRMS), neuromyelitis optica spectrum disorders (NMOsd), and neuropsychiatric systemic lupus erythematosus (NPSLE) patients. Blood-brain-barrier (BBB) disruption is one of the key pathological processes involved in various demyelinating diseases of the central nervous system (CNS) and is associated with shedding of cell adhesion molecules and S100B into the serum compartment. Therefore, making an assessment of serum levels of the above-mentioned molecules could provide information about disease pathogenesis, severity of BBB disruption, and disease activity. We recruited 42 RRMS, 19 NMOsd and 35 NPSLE patients. Subjects were treated with beta-interferons or glatiramer acetate (RRMS), oral steroids and/or azathioprine (NMOsd, NPSLE), other immunosuppressants (NPSLE), or antimalarials (NPSLE). The clinical condition of the patients was assessed using the Kurtzke Expanded Disability Status Scale for MS and NMOsd, and the Systemic Lupus Erythematosus Disease Activity Index for NPSLE. Serum levels of sVCAM-1, sPECAM-1, sICAM-1 and S100B were determined using enzyme-linked immunosorbent assay (ELISA). We found the lowest levels of sPECAM-1, sICAM-1 and S100B in sera from NMOsd patients. The highest levels of sPECAM-1 and sICAM-1 were observed in NPSLE, and in NPSLE and MS, respectively. There were no statistically significant differences in sVCAM-1 levels between the examined groups. In MS and NMOsd, there was a negative correlation between the EDSS score and the following molecules: sPECAM-1, sICAM-1 and S100B. We conclude that there is a different profile of blood-brain-barrier disruption reflected by cell adhesion molecules shedding in the spectrum of autoimmune CNS disorders with disseminated white matter lesions. These molecules could become new biomarkers to be used in CNS demyelinating diseases differential diagnoses and monitoring disease activity, but further studies on larger groups of patients are necessary.