Search Results (44)

Background: The pathogenesis of neuropsychiatric lupus erythematosus (NPSLE) is very complex and is associated with neuroinflammation and blood–brain barrier compromise. Experimental investigations of NPSLE have classically relied on spontaneous models. Recently, TLR7 agonist-induced lupus has been shown to exhibit similar neuropsychiatric manifestations to spontaneous ones. Cinnamon is a widespread spice and natural flavoring agent. It has been proven to modulate vascular endothelial tight junctions, neuroinflammation, and autoimmunity pathways, but it has never been tested in relation to lupus. Hypothesis/Purpose: In this pilot study, we aimed to explore the disease-modifying effect of Cinnamomum cassia on NPSLE in a TLR7 agonist-induced model. Study Design: An experimental design was followed in this study. Methods: Lupus was induced in C57BL/6J female mice via the direct application of imiquimod, a TLR7 agonist (5% imiquimod cream, 1.25 mg three times weekly), to the skin. Mice were divided into five groups (n = 8 per group): a sham group (S), a sham group supplemented with cinnamon (SC), an imiquimod-treated group (L), an imiquimod-treated group supplemented with cinnamon starting from induction (LC), and an imiquimod-treated group supplemented with cinnamon beginning two weeks prior to induction (CLC). This protocol was followed for six consecutive weeks. Cinnamomum cassia powder was administered orally at 200 mg/kg, 5 days per week. Results: Behavioral alterations were significantly ameliorated in the CLC group compared to lupus mice. Neuronal shrinkage and nuclear chromatin condensation were visible in the hippocampal cornu ammonis and dentate gyrus zones of lupus mice, with an increased expression of TLR7 and NLRP3, versus significantly less neurodegeneration and TLR7 and NLRP3 expression in the CLC group. In addition, the expression of the blood–brain barrier endothelial cell tight junction proteins claudin-1, occludin, and ZO-1 was abnormally modified in lupus mice and was restored in the CLC group. Moreover, while the cell–cell border delocalization of claudin-1 was documented in cultured blood–brain barrier endothelial cells treated with the plasma of lupus mice to a punctate intracytoplasmic fluorescence pattern, only cells treated with the plasma of the CLC group exhibited a complete reversal of this redistribution of claudin-1. Finally, cinnamaldehyde seemed to interact with TLR7 at multiple sites. Conclusions:Cinnamomum cassia seems to alleviate the pathogenesis of NPSLE. Supplementation with Cinnamomum cassia could be of great interest to modulate the activity and severity of the disease. Full article

This review aims to explore the role of immunotherapeutic strategies—primarily intravenous immunoglobulin (IVIG), plasma exchange (PLEX), and selected immunomodulatory agents—in the treatment of neurological and psychiatric disorders with suspected or confirmed autoimmune mechanisms. A central focus is placed on understanding the immunopathology of these conditions through the identification and characterization of disease-associated autoantibodies. Disorders such as autoimmune encephalitis, myasthenia gravis, limbic epilepsy, neuropsychiatric systemic lupus erythematosus (NPSLE), and certain forms of schizophrenia have shown clinical responses to immunotherapy, suggesting an underlying autoimmune basis in a subset of patients. The review also highlights the diagnostic relevance of detecting autoantibodies targeting neuronal receptors, such as NMDA and AMPA receptors, or neuromuscular junction components, as biomarkers that guide therapeutic decisions. Furthermore, we synthesize findings from published randomized controlled trials (RCTs) that have validated the efficacy of IVIG and PLEX in specific diseases, such as Guillain–Barré syndrome, and myasthenia gravis. Emerging clinical evidence supports expanding these treatments to other conditions where autoimmunity is implicated. By integrating immunological insights with clinical trial data, this review offers a comprehensive perspective on how immunotherapies may be tailored to target autoimmune contributors to neuropsychiatric disease. Full article

Background: Lymphopenia is associated with disease activity in adult patients with systemic lupus erythematosus (SLE), but no similar studies exist among children. Furthermore, lymphopenia has only been used as a parameter of disease activity in the SLE disease activity index (SLEDAI), but not as an independent marker. Objectives: This study aimed to ascertain lymphopenia as an independent marker related to disease activity in children with SLE. Methods: This was a retrospective cohort study on patients newly diagnosed with SLE. The data were collected from January 2009 to March 2017, including clinical manifestations, complete blood counts, anti-dsDNA, and Mexican-SLEDAI (MEX-SLEDAI) scores. Statistical analysis was performed using the Chi-square test, Student’s t-test, and ROC curve analysis. Results: A total of 103 patients, aged from 12 to 18 years, participated in the study. Of these, 58 patients (56.3%) exhibited lymphopenia. The most commonly observed clinical manifestations in the lymphopenia group included nephritis (72.4%), hypertension (24.1%), and leukopenia (36.2%), with p < 0.05. Furthermore, neuropsychiatric SLE was found exclusively in the lymphopenia group. A negative correlation was observed between lymphocyte counts and anti-dsDNA levels (r = −0.24), as well as between lymphocyte counts and the MEX-SLEDAI score (r = −0.63, with p < 0.05). The receiver operating characteristic (ROC) curve indicated that a lymphocyte count with a cut-off point of ≤1738/mm³ is significant for predicting anti-dsDNA reactivity. Conclusions: Lymphopenia is significantly correlated with higher anti-dsDNA levels and increased disease activity, potentially serving as an independent marker of disease activity in children with SLE. However, further research is needed. Full article

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a disorder with a poor prognosis characterized by psychiatric and neurological manifestations directly associated with systemic lupus erythematosus (SLE). Neutrophil ferroptosis has been identified as a significant contributor to neutropenia and disease progression in SLE, but its role in NPSLE remains unclear. Female MRL/lpr and MRL/Mpj mice were used. The selective ferroptosis inhibitor liproxstatin-1 and the acyl-CoA synthetase long-chain family member 4 (ACSL4) inhibitor rosiglitazone were administered separately. Assessments included behavioral testing, transmission electron microscopy (TEM), ELISA, Western blotting, RT-PCR, and Nissl staining. Our data showed that neurons in the brain parenchyma undergo ferroptosis, with decreased glutathione peroxidase 4 (GPX4) expression and increased levels of lipid peroxidation indicators and have the typical morphology of ferroptosis confirmed by transmission electron microscopy. Selective ferroptosis inhibitor liproxstatin-1 attenuated the neuropsychiatric manifestations, including depression-like and impulsive behaviors, of MRL/lpr mice. ACSL4 is the main enzyme in lipid metabolism. Our study further found that the utilization of rosiglitazone by inhibiting ACSL4 could also significantly attenuate neuropsychiatric manifestations of MRL/lpr mice. Moreover, blocking ACSL4 might considerably boost GPX4 levels and decrease lipid peroxidation indicators in NPSLE, with reduced neuronal damage, as well as reduced neuroinflammation. This study concluded that inhibiting ACSL4 could facilitate the recuperation of behavioral deficits by suppression of ferroptosis in NPSLE, implying that ACSL4 might be a potential new therapeutic focus for NPSLE. Full article

Background: Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder. Neuropsychiatric manifestations are frequently observed and are associated with increased morbidity and reduced quality of life. Magnetic resonance imaging (MRI) is the neuroimaging procedure of choice for investigation. High-resolution vessel wall imaging (HRVWI) is a neuroimaging methodology that allows active mapping of pathophysiological processes involving brain vessel walls. Methods: To exemplify the importance of HRVWI and its usefulness in patients with SLE, we carried out a scoping review (following PRISMA guidelines) using the PubMed and Embase databases. Results: We retrieved 10 studies that utilized HRVWI in neuropsychiatric SLE, including a total of 69 patients. The majority, 84% (58/69), were women, with ages ranging between 16 and 80 years (average 38.4 years). Approximately 46.3% (32/69) of patients had white matter lesions in the brain at the time of investigation, and 77% (53/69) had normal magnetic resonance angiography. Treatment with immunosuppressants led to the resolution of the majority of the findings. Conclusions: Imaging plays an important role in investigating neuropsychiatric SLE. HRVWI analysis is gaining more importance, with its ability to identify inflammation even if angiographic MRI sequences (3D TOF) are normal, allowing the institution of early immunosuppressant treatment and resolution of symptoms. Full article

The BALB/c model of pristane-induced lupus (PIL) exhibits cognitive impairment features resembling neuropsychiatric lupus (NPLSE). Osteopontin (OPN) is associated with disease activity in SLE; however, its involvement in NPLSE is not yet entirely determined. Our study aims to elucidate the contribution of full-length OPN (OPN-FL) plasma expression, OPN N-half, and Spp1 to cognitive impairment in the PIL mice model. A total of 76 female BALB/c mice were divided into pristane (P), pristane plus lipopolysaccharide (P plus LPS) and control (C) groups. In behavioral tests, the P group showed cognitive and visuospatial memory impairment. Elevated plasma OPN FL levels were found in P compared to C groups (177.7 ± 90.1 vs. 105.9 ± 56.8 ng/mL, p = 0.009) and OPN N-half was different between P and C groups (673.5 ± 144.6 vs. 624.5 ± 377.7 ng/mL, p = 0.028) and P plus LPS and C groups (624.5 ± 377.7 vs. 381.4 ± 205.0 ng/mL, p = 0.001). Anti-Sm correlated with OPN-FL (r = 0.269, p = 0.0150). The relative expression of Spp1 in the brain was 2.5 and 2.7-fold higher in P and P plus LPS groups, respectively. The evidence suggests that OPN is related to cognitive impairment in PIL mice and might play a relevant role in the detrimental neurological conditions of NPSLE. Full article

Excessive production and response to Type I interferons (IFNs) is a hallmark of systemic lupus erythematosus (SLE). Neuropsychiatric lupus (NPSLE) is a common manifestation of human SLE, with major depression as the most common presentation. Clinical studies have demonstrated that IFNα can cause depressive symptoms. We have shown that the kallikrein–kinin system (KKS) [comprised of kallikreins (Klks) and bradykinins] and angiotensin-converting enzyme inhibitors suppressed Type I IFN responses in dendritic cells from lupus-prone mice and human peripheral blood mononuclear cells. Tissue Klk genes are decreased in patients with lupus, and giving exogenous Klk1 ameliorated kidney pathology in mice. We retro-orbitally administered mouse klk1 gene-carrying adenovirus in the Murphy Roths Large lymphoproliferative (MRL/lpr) lupus-prone mice at early disease onset and analyzed immune responses and depressive-like behavior. Klk1 improved depressive-like behavior, suppressed interferon-responsive genes and neuroinflammation, and reduced plasma IFNα levels and proinflammatory cytokines. Klk1 also reduced IFNAR1 and JAK1 protein expression, important upstream molecules in Type I IFN signaling. Klk1 reduced bradykinin B1 receptor expression, which is known to induce proinflammatory response. Together, these findings suggest that Klk1 may be a potential therapeutic candidate to control IFNα production/responses and other inflammatory responses in SLE and NPSLE. Full article

Background/Objectives: We aimed to determine the prevalence and clinical correlations of mood disorders in a sample of systemic lupus erythematosus (SLE) patients. Hence, we hypothesized that the prevalence of mood disorders would be lower than reported in the literature and that patients would remain clinically stable and show less damage accrual despite low-dose corticosteroid prescription. Methods: In total, 92 SLE outpatients gave informed consent to participate in this cross-sectional study. Psychiatric and autoimmune clinical data were obtained, and a structured psychiatric interview was performed. The main clinical scales for the assessment of clinical symptomatology were included. To examine the potential relationships of presenting a mood disorder in SLE, clinical correlations and multivariate analyses were performed. Results: Mood disorders were the most prevalent disorder reported by SLE patients (16%), followed by adjustment disorders (5%). A significant proportion of patients presented psychosocial disturbances that did not meet the ICD-10 criteria for psychiatric diagnosis. According to the cut-off criterion for the Montgomery–Åsberg Depression Rating Scale (MADRS), up to 27% of the sample met the clinical criteria for depression. The multivariate analysis revealed a relationship between the presence of a mood disorder with total scores of the MADRS and the Young Mania Rating Scale (YMRS). Conclusions: The prevalence of mood disorders in patients with SLE was lower than previously reported. Although self-report clinical scales are useful for assessing clinical symptomatology, they should not be used in place of a comprehensive standardized interview conducted by a trained mental health specialist. Multidisciplinary teamwork is required for the early identification and therapeutic management of autoimmune patients with neuropsychiatric disorders. Full article

Wilson’s disease (WD) is a rare, autosomal recessive disorder of copper metabolism caused by pathogenic mutations in the ATP7B gene. Cellular copper overload is associated with impaired iron metabolism. Oxidative stress, cuproptosis, and ferroptosis are involved in cell death in WD. The clinical picture of WD is variable. Hepatic/neuropsychiatric/other symptoms may manifest in childhood/adulthood and even old age. It has been shown that phenotypic variability may be determined by the type of ATP7B genetic variants as well as the influence of various genetic/epigenetic, environmental, and lifestyle modifiers. In 1976, immunological abnormalities were first described in patients with WD. These included an increase in IgG and IgM levels and a decrease in the percentage of T lymphocytes, as well as a weakening of their bactericidal effect. Over the following years, it was shown that there is a bidirectional relationship between copper and inflammation. Changes in serum cytokine concentrations and the relationship between cytokine gene variants and the clinical course of the disease have been described in WD patients, as well as in animal models of this disease. Data have also been published on the occurrence of antinuclear antibodies (ANAs), antineutrophil cytoplasmic antibodies (ANCAs), anti-muscle-specific tyrosine kinase antibodies, and anti-acetylcholine receptor antibodies, as well as various autoimmune diseases, including systemic lupus erythematosus (SLE), myasthenic syndrome, ulcerative colitis, multiple sclerosis (MS), polyarthritis, and psoriasis after treatment with d-penicillamine (DPA). The occurrence of autoantibodies was also described, the presence of which was not related to the type of treatment or the form of the disease (hepatic vs. neuropsychiatric). The mechanisms responsible for the occurrence of autoantibodies in patients with WD are not known. It has also not been clarified whether they have clinical significance. In some patients, WD was differentiated or coexisted with an autoimmune disease, including autoimmune hepatitis or multiple sclerosis. Various molecular mechanisms may be responsible for immunological abnormalities and/or the inflammatory processes in WD. Their better understanding may be important for explaining the reasons for the diversity of symptoms and the varied course and response to therapy, as well as for the development of new treatment regimens for WD. Full article

Immunology and microbiology research has witnessed remarkable growth and innovation globally, playing a pivotal role in advancing our understanding of immune mechanisms, disease pathogenesis, and therapeutic interventions. This manuscript presents a comprehensive exploration of the key areas in immunology research, spanning from the utilisation of bacterial proteins as antibody reagents to the intricate realms of clinical immunology and disease management. The utilisation of bacterial immunoglobulin-binding proteins (IBPs), including protein A (SpA), protein G (SpG), and protein L (SpL), has revolutionised serological diagnostics, showing promise in early disease detection and precision medicine. Microbiological studies have shed light on antimicrobial resistance patterns, particularly the emergence of extended-spectrum beta-lactamases (ESBLs), guiding antimicrobial stewardship programmes and informing therapeutic strategies. Clinical immunology research has elucidated the molecular pathways underlying immune-mediated disorders, resulting in tailored management strategies for conditions such as severe combined immunodeficiency (SCID), neuropsychiatric systemic lupus erythematosus (NPSLE), etc. Additionally, significant efforts in vaccine development against tuberculosis and HIV are highlighted, underscoring the ongoing global pursuit of effective preventive measures against these infectious diseases. In summary, immunology and microbiology research have provided significant contributions to global healthcare, fostering collaboration, innovation, and improved patient outcomes. Full article

Systemic lupus erythematosus (SLE) is an autoimmune rheumatic condition characterized by an unpredictable course and a wide spectrum of manifestations varying in severity. Individuals with SLE are at an increased risk of cerebrovascular events, particularly strokes. These strokes manifest with a diverse range of symptoms that cannot be solely attributed to conventional risk factors, underscoring their significance among the atypical risk factors in the context of SLE. This complexity complicates the identification of optimal management plans and the selection of medication combinations for individual patients. This susceptibility is further complicated by the nuances of neuropsychiatric SLE, which reveals a diverse array of neurological symptoms, particularly those associated with ischemic and hemorrhagic strokes. Given the broad range of clinical presentations and associated risks linking strokes to SLE, ongoing research and comprehensive care strategies are essential. These efforts are critical for improving patient outcomes by optimizing management strategies and discovering new medications. This review aims to elucidate the pathological connection between SLE and strokes by examining neurological manifestations, risk factors, mechanisms, prediction and prevention strategies, management plans, and available research tools and animal models. It seeks to explore this medical correlation and discover new medication options that can be tailored to individual SLE patients at risk of stroke. Full article

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a complication of systemic lupus erythematosus with diverse clinical presentations sharing common features with variable neurologic disorders. Magnetic resonance imaging (MRI) may provide imaging evidence of structural brain abnormalities associated with symptoms of NPSLE. Serotonin syndrome is a toxidrome characterized by altered mental status, autonomic hyperactivity, and neuromuscular abnormalities. It is mostly caused by medications that increase serotonin and is rarely reported as a manifestation of neuropsychiatric lupus. We presented the case of a 24-year-old Taiwanese woman with a history of systemic lupus erythematosus diagnosed at 21 years of age. The initial clinical and laboratory presentations upon diagnosis included fever, arthritis, hypocomplementemia, positive antinuclear antibody, anti-double-stranded DNA antibody, and anti-ribosomal P antibody. Her condition once remained stable under oral glucocorticoids and immunosuppressants, but she developed sudden-onset consciousness disturbance, incoherent speech, and unsteady gait ten days before our assessment. A high fever of up to 39 °C with tremor and clonus occurred at the intensive care unit. Brain MRI revealed symmetric T2 hyperintensity without diffusion restriction over the bilateral globus pallidus. High-dose pulse glucocorticoid and rituximab were prescribed during her admission and the neuropsychiatric symptoms diminished upon treatment. No alternation in mental status or involuntary movements were noted at follow-up. Our patient was diagnosed with neuropsychiatric lupus, with clinical symptoms and image findings mimicking those of serotonin syndrome. Neuroimaging, such as MRI, detects various structural brain abnormalities and may provide pathophysiological evidence of clinical manifestations. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune condition that can seriously impair multiple organs including the nervous system, causing neuropsychiatric SLE (NPSLE), which encompasses a broad range of symptoms. Pathogenesis is not completely understood but is thought to involve inflammatory and vascular pathways. This comprehensive review discusses the complex nature and heterogeneity of NPSLE and the challenges in diagnosis and treatment that result from it. Diagnosis often requires a multidisciplinary approach with multiple assessments, including laboratory testing, imaging, and neuropsychological evaluations. Current treatments focus on managing symptoms through immunosuppressive and anti-thrombotic therapies tailored to the inflammatory or vascular nature of the specific NPSLE manifestations. This paper emphasizes the necessity for interdisciplinary approaches and further research to enhance diagnostic accuracy and treatment effectiveness. It also highlights the importance of understanding the underlying mechanisms of NPSLE to develop more targeted therapies, citing the need for high-quality studies and novel treatment agents. Full article

Background: Although mood disorders are prevalent among systemic lupus erythematosus (SLE) patients, they are usually underrecognized. This study aimed to estimate the prevalence of anxiety and depression among Saudi SLE patients. Methods: This cross-sectional study was conducted among SLE patients from July 2022 to June 2023 in the Eastern Province of Saudi Arabia. A self-reported questionnaire was used to collect the data through validated tools including the Hamilton Anxiety Rating Scale-A and the Beck Depression Inventory score. Results: There were 133 females (91.7%) and 12 males (8.3%) included in this study. Based on the HAM-A score, 45.5% of participants had an anxiety disorder, and according to the BDI score, 46.2% had a depression disorder. Anxiety and depression were significantly associated with a longer duration of SLE, unemployment status, smoking, and the presence of comorbidities. Moreover, the present study found a significant association between depression and male gender. Conclusion: This study found that Saudi SLE patients have a high prevalence of both anxiety and depression. Therefore, SLE patients should be screened for neuropsychiatric disorders during routine follow-ups and managed as early as possible. Full article

Neuropsychiatric Systemic Lupus Erythematosus (NPSLE) is a severe form of SLE involving the nervous system, resulting in neurological and psychiatric symptoms. Although research has shown that SLE patients often suffer from cognitive impairments, depression, and anxiety, there are no specialized guidelines for psychiatric assessment and treatment. This study aimed to investigate the progression of neuropsychiatric symptoms in SLE patients, explicitly focusing on anxiety and depression, over a year. It also aimed to identify potential biomarkers linked to NPSLE and explore the connection between NPSLE and the overall progression of SLE. Our research involved a longitudinal study with 65 adults diagnosed with SLE. Participants underwent various physical, biochemical, and serological tests and were assessed using disease activity indexes like BILAG-2004 and SLEDAI-2K. Participants also underwent psychological assessments using the Hamilton Anxiety and Depression Rating Scales. The study did not find any significant impact of antidepressant therapy on the evolution of anxiety and depression among participants. However, medications like Methotrexate and Plaquenil showed a substantial reduction in these symptoms. Moreover, anxiolytic therapy seems to influence depression in SLE patients. The study also noted that anxiety levels tend to increase over time but are not directly associated with SLE activity. This study concludes that although specific SLE medications can affect the level of anxiety and depression, the overall effectiveness of neuropsychiatric therapy in managing these symptoms is limited. The findings suggest that further research into the tailored management of NPSLE symptoms and a deeper understanding of the disease’s psychiatric aspects are needed. Full article