Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Ceccarelli, Fulvia; Perricone, Carlo; Pirone, Carmelo; Massaro, Laura; Alessandri, Cristiano; Mina, Concetta; Marianetti, Massimo; Spinelli, Francesca Romana; Valesini, Guido; Conti, Fabrizio

doi:10.1371/journal.pone.0196103

Cited by 39 publications

(50 citation statements)

References 43 publications

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“…This unique inflammatory change in the brain may account for the chronic non-fatal but disabling neurological status such as cognitive impairment and mood disorders in human SLE. A recently reported improvement of fatigue and cognitive impairment by treatment for SLE supports the idea that neuropsychiatric symptoms recognized as not attributable to SLE have immune-related mechanisms and that the correct treatment might ameliorate them [57, 58]. Further insights into the innate immune-related mechanisms of NPSLE will lead to the development of novel therapeutic strategies.…”

Section: Discussionmentioning

confidence: 90%

Unique primed status of microglia under the systemic autoimmune condition of lupus-prone mice

et al. 2019

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BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of various autoantibodies. This disease causes disabling neuropsychiatric symptoms even in the absence of apparent inflammation in the central nervous system (CNS), but the mechanisms involved remain unknown. Innate immune-mediated inflammation has attracted attention as a pathogenic mechanism in neuropsychiatric diseases.MethodsWe investigated the CNS of lupus-prone mice focusing on innate immunity. Three strains of lupus-prone mice, FcγRIIB−/−Yaa, an F1 hybrid of NZB and NZW (NZB/NZW) mice, and MRL/Faslpr (MRL/lpr) mice were used to analyze CNS immunopathology.ResultsFlow cytometry analysis demonstrated the numbers of brain CD45+ cells were increased compared with controls in lupus-prone mice. Upregulation of MHC class I and PDCA1 was observed in microglia and CD11b+ myeloid cells of lupus-prone mice, indicating they were activated in response to interferons (IFN). Microglial gene expression analysis of FcγRIIB−/−Yaa mice revealed the upregulation of IFN-responsive genes and inflammation-related genes including Axl, Clec7a, and Itgax, which were previously reported in neurodegenerative conditions and primed conditions. Upregulated chemokine gene expressions including Ccl5 and Cxcl10 were concurrent with increased numbers of T cells and monocytes, especially Ly6Clo monocytes in the CNS. Upregulation of Axl, Clec7a, Itgax, Ccl5, and Cxcl10 was also observed in NZB/NZW mice, indicating common lupus pathology. The primed status of microglia in FcγRIIB−/−Yaa mice was also demonstrated by morphological changes such as enlarged cell bodies with hypertrophic processes, and hyperreactivity to lipopolysaccharide. Immunohistochemistry of FcγRIIB−/−Yaa mice indicated reactive responses of astrocytes and vascular endothelium. Behavioral studies of FcγRIIB−/−Yaa mice revealed depressive-like behavior and heat hyperalgesia in the forced swim test and the tail-flick test, respectively.ConclusionsOur data indicated that microglia in lupus exhibit a unique primed phenotype characterized by the upregulated expressions of neurodegeneration-related genes and IFN-responsive genes. Interaction with peripheral cells and brain resident cells was presumed to orchestrate neuroinflammation. Targeting innate immune cells, such as microglia and monocytes, may be a promising therapeutic approach for neuropsychiatric SLE.

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Section: Discussionmentioning

confidence: 90%

Unique primed status of microglia under the systemic autoimmune condition of lupus-prone mice

et al. 2019

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“…For this study, fibromyalgia was studied as an example of type 2 symptoms and was determined using the 2011 ACR fibromyalgia diagnostic criteria. Fibromyalgia was considered present when the following criteria were met: 1) widespread pain score ≥7 and symptom severity score ≥5, or 2) widespread pain score ≥3 and symptom severity score ≥9 (21).…”

Section: Methodsmentioning

confidence: 99%

“…Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease characterized by diverse clinical manifestations that vary in intensity and severity (1). Along with symptoms directly related to inflammation, individuals with this condition commonly report symptoms of widespread pain, fatigue, cognitive dysfunction, and depression (2–5). Despite improved survival rates and short‐term outcomes over the last 50 years (6), patients with SLE continue to have lower health care–related quality of life and increased rates of disability, largely driven by the symptoms of chronic pain, fatigue, cognitive dysfunction, and depression (7,8).…”

Section: Introductionmentioning

confidence: 99%

Using Clinical Characteristics and Patient‐Reported Outcome Measures to Categorize Systemic Lupus Erythematosus Subtypes

Rogers

Eudy

Pisetsky

et al. 2021

Arthritis Care & Research

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Objective The type 1 and type 2 systemic lupus erythematosus (SLE) categorization system was recently proposed to validate the patients’ perspective of disease and to capture a more comprehensive spectrum of symptoms. The objective of this study was to characterize the clinical manifestations of SLE subtypes and to determine the correlation between the patient‐ and physician‐reported measures used in the model. Methods This was a cross‐sectional study of patients with SLE in a university clinic. Patients completed the Systemic Lupus Activity Questionnaire (SLAQ) and 2011 American College of Rheumatology fibromyalgia (FM) criteria. Active SLE was defined as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score ≥6, clinical SLEDAI score ≥4, or active lupus nephritis. We identified 4 groups: type 1 SLE (active SLE without FM), type 2 SLE (inactive SLE with FM), mixed SLE (active SLE with FM), and minimal SLE (inactive SLE without FM). Results In this cohort of 212 patients (92% female, mean age 45 years), 30% had type 1 SLE, 8% had type 2 SLE, 13% had mixed SLE, and 49% had minimal SLE. Regardless of SLE disease activity, patients with FM (21%), reported higher SLAQ scores, patient global assessment scores, and self‐reported lupus flare that resulted in discordance between patient‐ and physician‐reported measures. Conclusion Fatigue, widespread pain, sleep dysfunction, and mood disorders are common symptoms in SLE. Identifying these symptoms as type 2 SLE may be a method to improve patient communication and understanding. The level of type 2 SLE impacts patients’ perception of disease and self‐reported symptoms. The SLAQ may need to be reinterpreted based on the FM severity scale.

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“…In a recently published literature review with meta-analysis, complex attention, delayed verbal memory, language and verbal reasoning were the most compromised domains in SLE patients [26]. Finally, the 10-years follow-up in a large SLE cohort demonstrated the improvement of CI in 50% of patients [27].…”

Section: Discussionmentioning

confidence: 99%

Pragmatic language dysfunction in systemic lupus erythematosus patients: Results from a single center Italian study

et al. 2019

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BackgroundCognitive impairment (CI) in systemic lupus erythematosus (SLE) is a frequent neuropsychiatric manifestation affecting several domains, even in apparently asymptomatic patients. Current research revealed that the typical CI pattern affects frontal-subcortical circuit and thus executive functions. The impairment of non-literal language or pragmatic language (PL), including metaphors, idioms, inferences or irony has been well described in several conditions such as autism disorders, Parkinson’s disease, brain injury and even in earlier phases of neurodegenerative processes. Even if PL neuro-anatomy remains controversial, correlation between executive dysfunctions and non-literal language involvement has been reported both in traumatic injury and mild cognitive impairment patients. Nonetheless, no specific study has been performed to evaluate PL impairment in SLE patients so far.ObjectivesWe aimed at assessing the PL domain in a Italian monocentric SLE cohort in comparison to healthy controls, matched to age and education, through a specific battery, the batteria sul linguaggio dell'emisfero destro (BLED). Secondly, we focused attention on possible correlations between CI and clinical and laboratory SLE-related features.MethodsForty adult patients affected by SLE, according to the American College of Rheumatology (ACR) criteria, and thirty healthy subjects were enrolled consecutively in this cross-sectional study. The protocol included complete physical examination, extensive clinical and laboratory data collection (comprehensive of demographics, past medical history, co-morbidities, disease activity, chronic damage evaluation, previous and concomitant treatments) and cognitive assessment for five different domains: memory, attention, pragmatic language, executive and visuospatial functions. Self-reported scale for anxiety and depression were performed to exclude the influence of mood disorders on cognitive dysfunction.ResultsWe studied 40 Caucasian SLE patients [male (M)/ female (F) 3/37; mean±standard deviation (SD) age 45.9±10.1 years, mean±SD disease duration 120.8±81.2 months] and 30 healthy subjects (M/F 9/21; mean±SD age 41.3±13 years). According to the low level of disease activity and damage (mean±SD Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 1.3±2.3, mean±SD Systemic Lupus International Collaborative Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI) of 0.2±0.5), only 30% of patients was on glucocorticoid treatment at the study entry. PL was the most compromised domain in terms of Mean Domain Z scores. As for the Domain Cognitive Dysfunction score, a deficit of PL was observed in 45% of patients and was significantly more prevalent than memory, executive and visuospatial functions impairment (P = 0.0002, P = 0.0002 and P<0.000001, respectively). According to Global Cognitive Dysfunction score, 25% of patients experienced a mild impairment and 7.5% a moderate one. Anti-phospholipid antibodies positivity was significantly associated with memory impai...

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Cognitive dysfunction improves in systemic lupus erythematosus: Results of a 10 years prospective study

Cited by 39 publications

References 43 publications

Unique primed status of microglia under the systemic autoimmune condition of lupus-prone mice

Unique primed status of microglia under the systemic autoimmune condition of lupus-prone mice

Using Clinical Characteristics and Patient‐Reported Outcome Measures to Categorize Systemic Lupus Erythematosus Subtypes

Pragmatic language dysfunction in systemic lupus erythematosus patients: Results from a single center Italian study

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