Systemic Lupus Erythematosus Syndrome Research Articles

Blood-brain barrier damages and intrathecal synthesis of anti-N-methyl-D-aspartate receptor NR2 antibodies in diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

IntroductionAlthough neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the recalcitrant complications of the disease, its pathogenesis still remains unclear. Previous studies revealed that antibodies reactive with NMDA (N-methyl-D-aspartate) receptor NR2 (anti-NR2) are elevated in cerebrospinal fluid (CSF) of patients with diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE), which is usually more recalcitrant than neurologic syndromes of NPSLE (focal NPSLE). Two mechanisms have been implicated for the elevation of CSF IgG, including intrathecal synthesis and transudation through the damaged blood-brain barrier (BBB). The present study was designed in order to elucidate the roles of BBB function and intrathecal synthesis of anti-NR2 in the elevation of CSF anti-NR2 with regard to the severity in NPSLE.MethodsPaired serum and CSF samples were obtained from 81 systemic lupus erythematosus (SLE) patients when they presented active neuropsychiatric manifestations, and from 22 non-SLE control patients with non-inflammatory neurological diseases. The 81 SLE patients consisted of 55 patients with diffuse NPSLE, including 23 patients with acute confusional state (ACS), the severest form of diffuse NPSLE, and 26 patients with neurologic syndromes or peripheral nervous system involvement (focal NPSLE). IgG anti-NR2 and albumin were measured by ELISA. BBB function and intrathecal synthesis of anti-NR2 were evaluated by Q albumin and by CSF anti-NR2 index, respectively.ResultsCSF anti-NR2 levels, Q albumin and CSF anti-NR2 index were significantly higher in NPSLE than in non-SLE control. CSF anti-NR2 levels and Q albumin were significantly higher in ACS than in non-ACS diffuse NPSLE (anxiety disorder, cognitive dysfunction, mood disorder and psychosis) or in focal NPSLE, whereas there was no significant difference in CSF anti-NR2 index among the 3 groups. CSF anti-NR2 levels were significantly correlated with Q albumin in diffuse NPSLE (r = 0.3754, P = 0.0053).ConclusionsThese results demonstrate that the severity of BBB damages plays a crucial role in the development of ACS, the severest form of diffuse NPSLE, through the accelerated entry of larger amounts of anti-NR2 into the central nervous system.

Aspirin for prevention of preeclampsia in lupus pregnancy.

Preeclampsia, the onset of hypertension and proteinuria during pregnancy, is a common medical disorder with high maternal and fetal mortality and morbidity. The underlying pathology remains poorly understood and includes inflammation, endothelial dysfunction, and an unbalanced thromboxane A2/prostacyclin ratio. For women with systemic lupus erythematosus (SLE), particularly those with preexisting renal disease or with active lupus, the risk of developing preeclampsia is up to 14% higher than it is among healthy individuals. The mechanism is still unknown and the data for preventing preeclampsia in lupus pregnancies are rare. Modulating the impaired thromboxane A2/prostacyclin ratio by administration of low-dose aspirin appears to be the current best option for the prevention of preeclampsia. After providing an overview of the pathogenesis of preeclampsia, preeclampsia in lupus pregnancies, and previous trials for prevention of preeclampsia with aspirin treatment, we recommend low-dose aspirin administration for all lupus patients starting prior to 16 weeks of gestation. Patients with SLE and antiphospholipid syndrome should receive treatment with heparin and low-dose aspirin during pregnancy.

Concomitant occurrence of cervical myelopathy, cerebral infarction, and peripheral neuropathy in systemic lupus erythematosus: a case report.

Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease characterized by multiorgan involvement with diverse clinical presentations. Central nervous system involvement in neuropsychiatric syndromes of SLE (NPSLE), such as cerebrovascular disease and myelopathy, is a major cause of morbidity and mortality in SLE patients. The concomitant occurrence of myelopathy, cerebrovascular disease, and peripheral neuropathy in a patient with SLE has not yet been reported. We report on a 41-year-old woman with SLE who showed motor and sensory impairment with urinary retention and was diagnosed with cervical myelopathy and acute cerebral infarction by spine and brain magnetic resonance imaging and peripheral neuropathy by electrodiagnostic examination. Even though pathogenesis of NPSLE is not well elucidated, we assume that increased antibodies of anti-double stranded DNA (anti-dsDNA), presence of lupus anticoagulant and hypertension are risk factors that have caused neuropsychiatric lupus in this patient.

Refractory hemophagocytic syndrome in systemic lupus erythematosus successfully treated with intermittent intravenous cyclophosphamide: three case reports and literature review

We experienced three patients with refractory or severe hemophagocytic syndrome associated with the activity of systemic lupus erythematosus, so-called acute lupus hemophagocytic syndrome (ALHS). All patients were successfully treated with intermittent intravenous injections of cyclophosphamide (IVCY). In each patient, hemophagocytosis was found during bone marrow examination, and infectious causes of hemophagocytic syndrome were carefully excluded. Patients 1 and 2 were refractory to combination therapy with a high-dose corticosteroid and rituximab or cyclosporine and were successfully treated with additive IVCY. Patient 3 had very severe ALHS that developed after cardiac surgery but was successfully treated with a high-dose corticosteroid and IVCY. We conducted a literature review of adult ALHS and analyzed 54 cases reported from 2006 to 2013. Although the clinical and laboratory features were diverse, fever, bicytopenia or pancytopenia, and hyperferritinemia were almost universal. Including our 3 patients, a total of 16 have reportedly been treated with IVCY-containing regimens, and ALHS was successfully controlled in most of them without switching or adding other therapies. We suggest that combination therapy with IVCY and corticosteroids may be useful to treat severe or refractory ALHS.

High prevalence of restless legs syndrome in systemic lupus erythematosus

Introduction Background : data regarding the sleep dysturbancies in systemic lupus erytematosous (SLE) are scarce. Objective : the aim of this study is to determine the prevalence of restless legs syndrome (RLS) and sleep dysturbancies in systemic lupus erythematosus. Materials and methods prospective study on consecutive patients with SLE. We used a standardized questionnaire with face-to-face interview. RLS diagnosed were based on the criteria of the RLS Study Group. The severity of RLS was assessed by Restless Legs Syndrome Rating Scale and quality of life by Restless Legs Syndrome Quality of Life Instrument. Sleep was assesed by Pittsburg Sleep Quality Index and Epworth Sleepiness Scale. The patients had to choose from a list of terms which described the sensations in their legs. Results 42 patients with SLE (40 women) were included in the study, mean age 53.43 ± 22.69 years (limits 21–78). 17 patients (40.47%) met the criteria for RLS. Six patients describe frequency of occuring of RLS in 6–7 nights per week, 4 in 4–5, 3 in 1–3 nights, 2 in 2–4 times per month and 2 patients one time per month. Multivariate analyses showed that risk factors for RLS were age and disease duration. Severe insomnia was reported by 15 patients (35.71%). Conclusion the prevalence of RLS is high is SLE. The severity of disease is high and occurs in 58% more than 4 nights per week.

Discovery of biomarkers for systemic lupus erythematosus using a library of synthetic autoantigen surrogates

Antibodies to a wide range of self-antigens, including those directed against nucleic acids or nucleic acid-binding proteins are the essential biomarkers for diseases such as systemic lupus erythematosus (SLE). Highly complex libraries of nonamers consisting of N-substituted glycines (peptoids) were screened for compounds that bound IgG from patients with SLE and earlier, incomplete autoimmune syndromes. Peptoids were identified that could identify subjects with SLE and related syndromes with a high sensitivity (70%) and specificity (97.5%). Immobilized peptoids were used to isolate IgG from both healthy subjects and SLE patients that reacted with known RNA-binding proteins. In the case of SLE patients, the peptoid-purified IgG reacted with several autoantigens, suggesting that the peptoids are capable of interacting with multiple, structurally similar molecules. These results show that the measurement of IgG binding to peptoids can identify subjects with high levels of pathogenic autoantibodies.

Toll-like receptor 4 gene polymorphism 1196 C/T does not influence the risk of neuropsychiatric systemic lupus erythematosus in Polish population – a preliminary report

Recent data indicate that Toll-like receptors (TLRs) participate in various neuropathologic conditions, including ictogenesis, myelin disruptions associated with chronic alcohol abuse, behavioral and cognitive dysfunctions associated with alcohol-induced neuroinflammatory damage, and activation of microglia to reduce amyloid β deposits. As seizures and depression are well known neuropsychiatric syndromes in systemic lupus erythematosus (SLE) the aim of the study was to investigate whether TLR4 gene polymorphism 1196C/T (rs4986791, Thr399Ile) was a candidate for susceptibility of development of neuropsychiatric systemic lupus erythematosus (NPSLE). The study covered 60 patients with SLE and 100 healthy individuals. TLR4 1196C/T genotyping was performed by real-time polymerase chain reaction with the SimpleProbe. The SLE group comprised 86.7% of patients with wild-type homozygotes CC and 13.3% heterozygotes CT and no homozygotes TT. The control group consisted of 85% wild-type homozygotes CC, 15% heterozygotes CT and no homozygotes TT. The frequencies of genotype and allele distribution in SLE patients did not differ significantly from those of the control subjects. The probability of describing the possible risk of SLE imputed to genotype did not significantly differ in comparison with the healthy individuals (p = 0.77, odds ratio = 0.87, 95% confidence interval 0.34-2.19). A significant genotype association of genotype CC with arthritis was found in SLE patients (p = 0.02). It was further confirmed by a significant association of a dominant allele C with arthritis (p = 0.02). No association between CC and CT genotypes of TLR4 1196C/T and NPSLE was found. Allele distribution of TLR4 1196C/T also was not associated with NPSLE. No other significant differences were found in genotype and allele frequencies regarding clinical manifestation of SLE patients. In the Polish population of SLE patients, 1196C/T polymorphism of TLR4 gene does not increase the risk of development of NPSLE; however, genotype CC and a dominant allele C is associated with arthritis in the course of SLE.

Systemic lupus erythematosus–associated neutrophilic dermatosis—an underrecognized neutrophilic dermatosis in patients with systemic lupus erythematosus

Neutrophilic dermatoses are an uncommon manifestation of lupus. We describe the clinical and histopathologic features of 14 patients with systemic lupus erythematosus (SLE) and neutrophilic dermatoses, 2 of whom had no prior history of SLE. Thirteen patients were female, ranging in age from 27 to 62 years (mean age, 42.8 years). One patient was a 20-year-old man. Most lesions were described as erythematous papules and plaques and showed annular morphology in 6 patients and a photodistribution in 2 patients. Histopathologic examination in all cases showed an interstitial neutrophilic infiltrate with leukocytoclasis that ranged from sparse in 5 cases and moderate to dense in 9 cases. With one exception, those cases with moderate to dense infiltrates resembled Sweet's syndrome at scanning magnification. Two cases resembled bullous SLE, and 1 case showed overlapping features of bullous SLE and Sweet's syndrome. Interface changes were seen in 8 patients, which were subtle and vacuolar in 7. One case was associated with a florid interface tissue reaction. Dermal mucin was seen in 4 cases and was a prominent feature in only one of these. One case showed a minute discrete focus resembling palisaded neutrophilic and granulomatous dermatitis. It is important to consider SLE-associated neutrophilic dermatosis in the differential diagnosis of neutrophilic tissue reactions particularly because some patients will have no prior history of lupus. It is also important to be aware of the broad histologic spectrum that may be encountered in SLE-associated neutrophilic dermatosis, ranging from subtle paucicellular lesions to florid Sweet's-like lesions associated with a dense neutrophilic infiltrate.

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus following methylprednisolone: report of two cases

Posterior reversible encephalopathy syndrome in systemic lupus erythematosus following methylprednisolone: report of two cases

SLE and metabolic syndrome

Metabolic syndrome (MetS) is a recently defined clustering of cardiovascular risk factors associated with insulin resistance and an increased risk of future type II diabetes mellitus and cardiovascular disease (CVD). Systemic lupus erythematosus (SLE) patients have an increased prevalence of MetS and an increased prevalence of insulin resistance. Chronic inflammation may predispose to these complications in SLE and there is also evidence that corticosteroid therapy also contributes, although this finding has not been as consistent as would be predicted from the known metabolic effects of corticosteroids. MetS may represent a good model in which to begin to understand how SLE drives an increased risk of CVD. For now, the utility of identifying MetS in patients is to identify a subset in which more focused lifestyle interventions should be targeted and in whom medication review and adjustment (especially corticosteroid doses) should be considered to help modify future CVD risk.

Guillain–/INS;Barre syndrome in systemic lupus erythematosus: Case report

Guillain–/INS;Barre syndrome in systemic lupus erythematosus: Case report

Posterior Reversible Encephalopathy Syndrome in Systemic Lupus Erythematosus

Posterior reversible encephalopathy syndrome (PRES) is an underrecognized and reversible condition in systemic lupus erythematosus (SLE) that could mimic neuropsychiatric lupus. Identification of any distinct clinical patterns is important as one would need to escalate rather than decrease or discontinue immune suppression in neuropsychiatric lupus. We retrospectively identified and described 5 patients with SLE who were hospitalized and diagnosed with PRES from 2008 to 2013 in a tertiary medical center and reviewed relevant literature. Posterior reversible encephalopathy syndrome in SLE occurred in young women with age distribution from 19 to 37 years. At the time of presentation, all had hypertension (systolic blood pressures ranging from 150 to 220), moderate to severe disease activity (Systemic Lupus Erythematosus Disease Activity Index scores ranging from 11 to 41), and prototypical magnetic resonance imaging findings of PRES and nephritis (4 of 5 patients had biopsy-proven lupus nephritis). Seizures, headache, and confusion were the most common clinical symptoms. One patient had intracerebral hematoma, and 2 patients had cerebral petechial hemorrhages. All patients improved without any neurological deficits, with a mean hospital stay of 11.2 days. Systemic lupus erythematosus should be considered in the differential diagnosis of patients who present with PRES. One should have a low threshold for magnetic resonance imaging especially when neurological symptoms occur in young women with or without an established diagnosis of SLE and especially among those with active SLE, lupus nephritis, renal failure, and/or poorly controlled hypertension. Given the good prognosis of PRES in SLE patients with early supportive treatment, prompt recognition is crucial to institute appropriate management.

Hydroxychloroquine-Induced Pigmentation in Patients With Systemic Lupus Erythematosus

Hydroxychloroquine-induced pigmentation is not a rare adverse effect. Our data support the hypothesis that hydroxychloroquine-induced pigmentation is secondary to ecchymosis or bruising. To describe the clinical features and outcome of hydroxychloroquine (HCQ)-induced pigmentation in patients with systemic lupus erythematosus (SLE). In a case-control study conducted at a French referral center for SLE and antiphospholipid syndrome, 24 patients with SLE, with a diagnosis of HCQ-induced pigmentation, were compared with 517 SLE controls treated with HCQ. The primary outcome was the clinical features of HCQ-induced pigmentation. Skin biopsies were performed on 5 patients, both in healthy skin and in the pigmented lesions. The statistical associations of HCQ-induced pigmentation with several variables were calculated using univariate and multivariate analyses. Among the 24 patients, skin pigmentation appeared after a median HCQ treatment duration of 6.1 years (range, 3 months-22 years). Twenty-two patients (92%) reported that the appearance of pigmented lesions was preceded by the occurrence of ecchymotic areas, which gave way to a localized blue-gray or brown pigmentation that persisted. Twenty-three patients (96%) had at least 1 condition predisposing them to easy bruising. Results from skin biopsies performed on 5 patients showed that the median concentration of iron was significantly higher in biopsy specimens of pigmented lesions compared with normal skin (4115 vs 413 nmol/g; P < .001). Using multivariate logistic regression, we found that HCQ-induced pigmentation was independently associated with previous treatment with oral anticoagulants and/or antiplatelet agents and with higher blood HCQ concentration. Hydroxychloroquine-induced pigmentation is not a rare adverse effect of HCQ. Our data support the hypothesis that HCQ-induced pigmentation is secondary to ecchymosis or bruising.

TNF Blockade and Cutaneous Lupus Erythematosus: Where do We Stand and Where are We Going?

Anti-TNF - a agents are used as a reserve treatment for cases of severe psoriasis and psoriatic arthritis that do not respond to conventional therapies. The current use of anti-TNF -a for systemic lupus erythematosus (SLE) and cutaneous lupus erythematosus (CLE) is limited by the clinical observations of the induction of a SLE syndrome. Despite the great number of SLE-like syndromes reported as a side effect of anti-TNF - a blockers, only very few cases of CLE are believed to be a consequence of these drugs. Moreover, on the basis of clinical and laboratory data, anti-TNF -a blockers could be considered as an option for CLE refractory to conventional

FRI0327 Brain mri findings in patients with diffuse psychiatric/neuropsychological syndromes in systemic lupus erythematosus

BackgroundNeuropsychiatric manifestations in systemic lupus erythematosus (NPSLE) are one of the most difficult complications of the disease, especially diffuse psychiatric/neuropsychological syndromes (diffuse NPSLE). For the evaluation and the diagnosis of...

AB0659 Oral manifestations, oral health status, and salivary changes in iraqi systemic lupus erythematosus

BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease associated with significant morbidity and mortality (1). Sicca symptoms are frequent in SLE which may be related to concomitant occurrence of...

SAT0231 Diffusion tensor imaging and cogntive performance in NPSLE

BackgroundOne of the most common manifestations of Neuropsychiatric SLE (NPSLE) is cognitive dysfunction, which is present in up to 80% of patients [1]. NPSLE presents a diagnostic challenge as it...

Sweet's syndrome associated with systemic lupus erythematosus: A case report and review of the literature

A 35-year-old Japanese female patient with systemic lupus erythematosus (SLE) presented with fever, erythematous papules and nodules, and polyarthralgia. Skin biopsy of a nodule was compatible with Sweet's syndrome. The papules/nodules were well treated with an oral glucocorticoid. Thirty cases of Sweet's syndrome associated with lupus erythematosus (LE) have been reported in the published work. The mean age was 34.2years. They showed a higher male ratio (male:female, 1:2) compared with patients with SLE (1:9) and Sweet's syndrome (1:3.7). Sweet's syndrome may occur as a manifestation of LE, and a moderate dose of an oral glucocorticoid will result in a good response.

DNA-dependent Activator of Interferon-regulatory Factors (DAI) Promotes Lupus Nephritis by Activating the Calcium Pathway

Macrophage M2b polarization conferred by self-DNA immunization initiates and propagates lupus nephritis. Knockdown of DNA-dependent activator of interferon-regulatory factors (DAI) ameliorates SLE syndrome via blunting macrophage M2b polarization. DAI functions as a DNA sensor in self-DNA-induced macrophage M2b polarization and lupus nephritis. We disclose the mechanism by which self-DNA induces macrophage M2b polarization and lupus nephritis DNA-dependent activator of interferon-regulatory factors (DAI) functions as a cytoplasmic DNA sensor that activates the innate immune system. We previously found that activated lymphocyte-derived self-apoptotic DNA (ALD-DNA) immunization led to pathological macrophage activation and M2b polarization, which could initiate and propagate murine lupus nephritis. However, the specific DNA sensor(s) as well as underlying molecular mechanisms involved in ALD-DNA-induced macrophage M2b polarization in systemic lupus erythematosus (SLE) disease remains unknown. In this study, we reported that DAI expression was significantly increased in SLE patients as well as in lupus mice. Gain- and loss-of-function studies revealed that DAI was involved in ALD-DNA-induced macrophage activation and M2b polarization. Moreover, ALD-DNA notably induced dimerization/oligomerization of DAI and consequently activation of nuclear factor κB (NF-κB) and interferon regulatory factor 3 (IRF3) signaling pathways via calcium signaling, resulting in macrophage activation and M2b polarization. More importantly, blockade of DAI in vivo or selective knockdown of DAI in macrophages could ameliorate SLE syndrome via blunting macrophage M2b polarization and inhibiting inflammatory response in lupus mice. Our results suggest that DAI could function as a DNA sensor and a regulator in ALD-DNA-induced macrophage M2b polarization and lupus nephritis, providing the possible molecular mechanisms involved in ALD-DNA-induced macrophage M2b polarization in SLE disease and making DAI as a potential therapeutic target for the treatment of SLE.

TRIM dsDNA sensor to restrict innate immune response

The innate immune system, also known as the non-specific immune system, is the first line of defense utilized by the host to provide protection against infection by organisms. In order to combat infection by bacteria, viruses or fungi, host cells have evolved a repertoire of sophisticated systems to sense infection and trigger innate immune responses, through the engagement of Toll-like receptors (TLRs) or other pattern-recognition receptors on the cell surface.1 Upon the activation of pattern-recognition receptor, various immune responses are initiated, leading to the production of a variety of cytokines and pro-inflammatory factors such as type I interferons (IFN-α and IFN-β) by dendritic cells (DCs).2 However, these normally beneficial responses may lead to pathological consequences if they are not tightly controlled. For example, systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic sclerosis and Sjogren's syndrome, develop in response to continuous inflammatory signals, which create a feedback amplification loop for autoimmune responses.3