Systemic Lupus Erythemathosus Research Articles

Dietary oleuropein and its new acyl-derivate attenuate murine lupus nephritis through HO-1/Nrf2 activation and suppressing JAK/STAT, NF-κB, MAPK and NLRP3 inflammasome signaling pathways

Systemic lupus erythemathosus (SLE) is a chronic inflammatory and autoimmune disease which can affect multiple organ systems, without an effective and safe treatment. Olive leaf extracts are of special interest for their therapeutic effects. Oleuropein (OL) is the most abundant constituents of olive leaf extract and possesses many beneficial properties. In this study, we evaluated the effects of dietary OL and its new derivate, peracetylated oleuropein (Per-OL), in a pristane-induced SLE model. Mice received an injection of pristane or saline solution and were fed with experimental diets: enriched with OL and Per-OL. The levels of proinflammatory cytokines and markers were evaluated by enzyme-linked immunosorbent assay. The protein expressions of inducible nitric oxide synthase, microsomal prostaglandin E synthase 1, heme oxygenase (HO-1), nuclear factor E2-related factor 2 (Nrf2), mitogen-activated protein kinases (MAPKs), Janus kinase/signal transducer and activator of transcription (JAK/STAT), nuclear transcription factor-kappa B (NF-κB) and inflammasome nucleotide-binding domain, leucine-rich repeats-containing family, pyrin domain-containing-3 (NLRP3) pathways activation were determined in kidneys by Western blot. OL and Per-OL significantly reduced renal damage and decreased serum matrix metalloproteinase 3 and prostaglandine E2 kidneys levels. Our findings indicate that Nrf2 and HO-1 antioxidant protein expressions were up-regulated in mice fed with OL and Per-OL diets, whereas the activation of JAK/STAT, MAPK, NF-κB and NLRP3 inflammasome pathways was significantly ameliorated. These results suggest that OL and Per-OL supplementation might provide a new alternative approach as a preventive/palliative treatment of nephritis in SLE management.

Lupus Cofactor Effect of Mixing Study: Example of a Case Report and Revisit on Theoretical Aspects

Background: Lupus anticoagulants (LA) are in vitro inhibitors paradoxically associated with thrombosis and performing coagulation test on a mixture of test plasma and pooled normal plasma to evidence this property is a mainstay in LA detection.
 Case report: We report a 20-year-old man who presented with one week history of fever, associated with productive cough, jaundice, and lethargy. He was a known case of systemic lupus erythemathosus for 10 years. Isolated activated partial thromboplastin time (APTT) were prolonged. Interestingly, the APTT mixing study was not corrected and showed more prolonged results than baseline APTT. LA study showed presence of a strong LA, which is related to the underlying autoimmune disease.
 Discussion: This case focuses on the ‘rebound phenomenon’ in APTT mixing test, from a strong LA that gives a cofactor inhibitory effect to the entire test system after adding the normal plasma.
 Bangladesh Journal of Medical Science Vol.18(2) 2019 p.430-433

Altered Th17/Treg Ratio in Peripheral Blood of Systemic Lupus Erythematosus but Not Primary Antiphospholipid Syndrome.

Introduction: The role of the immune response in the pathogenesis of antiphospholipid syndrome (APS) remains elusive. It is possible that differences in the frequencies of Th17 cells and/or defects in the immunoregulatory mechanisms are involved in the pathogenesis of APS. Our aim was to determine the peripheral blood Th cells phenotype and the circulating cytokine profile in patients with primary APS (pAPS) and compare it with systemic lupus erythemathosus (SLE) as disease control group.Methods: The frequencies of circulating regulatory T cells (Tregs) were determined in PBMCs from 36 patients with pAPS by flow cytometry. As control groups we included 21 age- and gender-matched healthy controls (HC) and 11 patients with SLE. The suppressive capacity of Tregs was evaluated in vitro by coculture assay. On the other hand, intracellular cytokine production was assessed in Th1, Th2, and Th17 cells and circulating IL-6, IL-10, and IL-35 were measured by Cytometric Bead Array and ELISA. The quantification of Th master gene expression levels was performed by real time quantitative PCR.Results: pAPS patients and SLE patients did not show differences in the percentage or number of Tregs compared to HC. The suppressive capacity of Tregs was also similar in the three study group. Instead, we found higher FoxP3·mRNA expression levels in pAPS patients and HC than SLE patients. Regarding the Th17 response, patients with pAPS and HC showed a significantly lower frequency of circulating Th17 cells than SLE. However, no differences were observed in the Th1 response between patients and controls. Thus, increased Th17/Th1 and Th17/Treg ratios were found in SLE patients but not in pAPS patients. pAPS and SLE patients had higher serum IL-6 levels than HC but there was not difference between both disease groups. Besides, a significant increase in the immunosuppressive cytokine levels was observed only in pAPS as compared to HC.Conclusions: Our data demonstrate an increased inflammatory profile of peripheral blood CD4+ T cells from SLE as compared with pAPS mostly due to an increased Th17 response. In conclusion, there seems not to be a direct pathogenic role for Th cells in pAPS but in SLE.

Antiinflamatory and antidepressive activities of Extract Curcuma xanthorrhiza Roxb in Systemic Lupus Erythematosus

Systemic Lupus Erythemathosus is an autoimmune, inflammatory, chronic disorder characterized by multiorgan system involvement. Depression and anxiety are frequent complaints among patients with lupus erythematosus, so antidepressive treatment should be an important element of the therapy of patients with lupus erythematosus. Research into curcumin’s potential as a treatment for depression is still in its infancy, although several potential antidepressant mechanisms of action have been identified. 4-weeks double-blind, placebo-controlled clinical trial was conducted in 14 SLE patients (10 as treatment group and 4 as control group) The BDI ( Beck Depression Inventory) score was calculated and TNF α concentration was measured in the serum subjects before and after treatment. Correlation between TNF α concentration and BDI was assessed . After 4 weeks treatment, the TNF α concentration from subjects in treatment group were significantly lower than before ( p <0.001) but the BDI score were not significantly lower than before (p = 0.059). The TNF α concentration and BDI score showed positive correlation, p = 0,024 . T his study demonstrate that Curcuma xanthorrhiza Roxb extract can decrease serum TNF α concentration and reduce clinically symptoms of depression in SLE patients

Limbic encephalitis with phenotypic NMDA receptor antibodies in patients with de novo diagnosis of Systemic Lupus Erythematosus. Case report

Malignancy-associated limbic encephalitis was first described in 1968. Since then, cases have been reported in association with the Herpes Simplex virus, Hashimoto's encephalopathy, lupus, Sjögren's syndrome and paraneoplasias. A syndrome with prominent psychiatric symptoms was described in 2005: consisting of memory loss, reduced level of consciousness and central hypoventilation in four young women with ovarian teratoma and antibodies against an antigen highly expressed in the hippocampus.Shortly afterwards, these patients were found to have autoantibodies against NMDA receptor NR1 (GluN1) subunit. This discovery has been of the greatest importance in clinical practice since it identifies a devastating, life-threatening neurological disorder that is treatable. In 2007, it was recognised as a nosologic entity and today it is the most common cause of autoimmune encephalitis after disseminated subacute encephalomyelitis.Case report presentation of a patient exhibiting almost all the clinical symptoms described in the syndrome characterised by NMDA receptor-associated encephalitis. Moreover, a neuroradiological correlation was found, with involvement of limbic structures seen on brain magnetic resonance imaging.Reasonable exclusion was made of the presence of neoplasia and neuroinfection, and clinical and immunological criteria of systemic lupus erythemathosus were found, helping with the categorisation of lupus-associated limbic encephalitis.Mortality due to limbic encephalitis is 25%, and 75% of patients may have permanent sequelae.Given adequate response to immunosuppressive therapy, early and correct recognition are critically important.

EFFECTIVITY AND RENAL SAFETY OF CYCLOSPORINE AND METHYLPREDNISOLONE COMBINATION THERAPY IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE)

Cyclosporine and methylprednisolone combination are second line therapy for moderate to severe systemic lupus erythemathosus. Some study suggest that the combination were effective to decrease of systemic lupus erythematosus disease activity. But record from the study, cyclosporine cause nephrotoxicity side effect. Therefore, this study should be considered to monitore therapy effect on disease activity and renal side effect. The aim of this study is to analyze the effect of cyclosporine and methylprednisolone combination therapy on disease activity in systemic lupus erythematosus (SLE) assessed by MEX-SLEDAI and renal side effect assessed by creatinine, ureum and proteinuria. A cohort, observational prospective study was conducted to determine the effect of cyclosporine and methylprednisolone combination therapy on disease activity of SLE and renal side effect of this combination. Patients who met criteria were given cyclosporine and methylprednisolone combination that normally renal function tests. MEX-SLEDAI score, creatinine, ureum and proteinuria were measured for fourth times (one time in one mounth), before study, 1st mounth, 2nd mounth, and 3rd mounth. The study comprised 9 patients SLE were given cyclosporine and methylprednisolone combination that normally renal function tests. All patients were female and had productive age. At 3rd mounth, there was increase patients who had MEX-SLEDAI score &lt;2 (55,6%) and one patient (11,1%) had increase of creatinine, ureum and proteinuria. In conclusion, cyclosporine and methylprednisolone combination therapy showed the effectiveness and safety in 88,9% patients and renal dysfunction in 11,1% patients.

Ficolin Gene Polymorphisms in Systemic Lupus Erythematosus and Rheumatoid Arthritis.

Systemic lupus erythemathosus (SLE) and rheumatoid arthritis (RA) are complex autoimmune diseases characterized by an immune balance breakdown and by chronic inflammation. Several findings link SLE and RA development with the complement system and ficolin components have emerged as candidates for disease development. Since genetic association studies with ficolin genes in SLE and RA have not yet been conducted in a Brazilian population, the aim of this study was to determine whether polymorphisms of ficolin-1(FCN1) and ficolin-2 (FCN2) genes are associated with SLE and RA susceptibility as well as disease manifestation. Two SNPs within FCN1 (rs2989727 and 1071583) and three in FCN2 (rs17514136, rs3124954, and rs7851696) were studied in 208 SLE and184 RA patients as well as 264 healthy individuals in a Southeast Brazilian population. For SLE patients, the FCN2 rs17514136 SNP was associated with a more severe disease (SLICC) (p = 0.0067). Furthermore, an association between the occurrence of nephritis and the T/T genotype for FCN2 rs3124954 SNP (p = 0.047, OR = 3.17, 95%CI = 1.34-7.5) was observed. No association was observed between the studied polymorphisms and RA development. Thus, our data support involvement of the FCN2 gene in the SLE phenotype.

Cardiovascular disease in psoriatic post-menopausal women.

It is generally accepted that the risk of cardiovascular disease (CVD) in women is significantly increased after the menopause. Hormonal changes associated with the menopausal transition may also alter the course of autoimmune diseases. It has been reported that menopause may exacerbate the symptoms of rheumatoid arthritis, systemic sclerosis and giant cell arteritis, but attenuate the course of systemic lupus erythemathosus. There is a growing body of literature indicating that the course of psoriasis may be altered by menopausal hormone changes. Considering the fact that both psoriasis and menopause are independent risk factors for CVD, and that menopause may exacerbate the course of psoriasis, a possible additive effect between these two conditions may be crucial for proper monitoring and treatment of peri- and post-menopausal psoriatic patients. The aim of this study is to analyse potential relationship between psoriasis, menopausal status and risk of CVD. A retrospective analysis of the Clalit Health Services database was performed in an attempt to provide new data and the available literature concerning these issues was reviewed. Data on cardiovascular events in 10 872 female psoriatic patients and 19 471 controls were extracted and compared. In both psoriatic and control patients the association of CVD increased with age. The association of CVD was significantly greater in psoriatic patients, but no significant differences were found between any of age groups. The association of psoriasis and CVD in women increases with age but there is insufficient evidence to confirm that menopause increases the risk of psoriasis. Further studies directly addressing this issue are needed.

AB0503 Suicide and Suicide Attempts in A Cohort of SLE Patients

BackgroundSuicidal intent is believed to be more prevalent amongst systemic lupus erythemathosus (SLE) patients than in the general population. Depression is often present in SLE patients and can be a...

AB0524 Comparison of the Clinical Features between Patients with Primary and Secondary Antiphospholipid Syndrome: Results from the Serbian National Cohort Study

ObjectivesAntiphospholipid syndrome (APS) patients suffer from various clinical manifestations with the presence of antiphospholipid antibodies (aPL). APS may manifest itself as a primary disease (PAPS) or as a secondary disease...

SAT0221 Survival in lupus patients with end-stage renal disease: A brazilian cohort

BackgroundTen to twenty-five percent of systemic lupus erythemathosus (SLE) patients will progress to end-stage renal disease (ESRD). Data about the survival rate of lupus patients on dialysis is controversial.ObjectivesThe present...

AB0367 Lymphocyte b depletion and moderate to severe activity in patients with systemic lupus erythemathosus

Background: INTRODUCTIONRituximab (RTX) induces a rapid and almost complete depletion of B cells in peripheral blood. It is used for patients with poor response to other therapies. The pharmacologic effect...

FYB gene polymorphisms are associated with susceptibility for systemic lupus erythemathosus (SLE)

Systemic Lupus Erythematosus (SLE) is a multifactorial autoimmune disease affecting different organs or systems. Several genes have been associated with SLE susceptibility so far. A previous study has reported, in SLE patients, a differential expression of Fyn Binding Protein gene (FYB), encoding for a protein participating in the T cells signaling cascade and in the interleukin-2A expression modulation. This study investigates the association of 10 FYB SNPs with differential susceptibility to SLE in 143 SLE patients and 184 controls from Southern Brazil. Significant differences were observed when comparing allele and genotype frequencies distribution in patients and controls: the T allele for rs6863066 C>T SNP and C for rs358501 T>C SNP were significantly more frequent in SLE patients than in controls (p=0.0002 and p=0.008) and associated with an increased risk for SLE (OR=1.93 and OR=1.69). The frequencies of rs6863066 C/T and T/T and rs358501 C/C genotypes were significantly higher in patients than in controls (p=0.001, p=0.006 and p=0.008). A significant association was also found for the rs6863066-rs358501 T-T and T-C haplotypes (OR=2.06, p=0.002 and OR=2.93, p=0.001). When considering clinical and laboratorial manifestations, an association was found between rs2161612 G allele and G/G genotype and hematological alterations (p=0.008) and rs379707 A/C genotype and anti-dsDNA (p=0.01). In conclusion, our findings indicate an association between polymorphisms located in FYB gene and SLE, suggesting their possible involvement in disease susceptibility and clinical manifestations.

Impaired serum cholesterol efflux capacity in rheumatoid arthritis and systemic lupus erythematosus

ObjectivesThe marked cardiovascular risk in autoimmune diseases is only partly explained. The capacity of high-density lipoproteins (HDL) to promote cell cholesterol efflux is a property with a well-known anti-atherogenic significance,...

A meta-analysis of mortality in rheumatic diseases

IntroductionData reporting mortality in rheumatic diseases vary widely. The objective of this systematic review and meta-analysis of published data is to provide an accurate overview of the current risk of mortality in rheumatic diseases. MethodsSystematic review and meta-analysis of published studies identified by a sensitive search using free text and MeSH synonyms of “mortality” and of “rheumatic diseases”, in general and by specific diagnoses. Eligibility criteria were (1) study population with rheumatoid arthritis, systemic lupus erythemathosus, systemic sclerosis, vasculitis, osteoarthritis, osteoporosis, dermatomyositis, or spondyloarthritis; (2) outcome of interest mortality, reported as an standardized mortality ratio (SMR), or easily calculated from data reported; and (3) cohorts or longitudinal observational studies. Assessment of risk of bias relied on the New Castle-Ottawa scale for cohorts; only moderate to high quality studies were included. Separate meta-SMRs were calculated for specific diagnoses. Heterogeneity was studied with meta-regression. ResultsA total of 32 studies were included, none in spondyloarthritis or osteoarthritis. The overall pooled SMR was 2.03 (95% confidence interval (CI) 1.79–2.29), ranging from 1.36 in psoriatic arthritis to 4.80 in vasculitis. The largest individual overall SMR came from studies on inflammatory diseases, and the specific SMR were very high for infections and pulmonary events. Heterogeneity between studies was large; however, the analysis of such heterogeneity within diseases did not provide any association with the collected variables. ConclusionsBased on our results and on the good quality of the included studies, we can conclude that rheumatic diseases increase in general the risk of death, and especially inflammatory diseases.

Familial amyloidotic polineuropathy and systemic lupus

Familial amyloidotic polineuropathy is a genetic disorder, leading to systemic amyloid deposits, manifested as sensory-motor and autonomic neuropathy. In the Portuguese classical form, the disease is evident at a young age, and causes death if no specific treatment is received. Variability in penetrance, age of onset and clinical course has been published; environmental and genetic factors are believed to contribute to this variability. The authors report a case of a 51-year-old white female, with a medical history of acquired angioedema, late-onset familial amyloidotic polineuropathy and systemic lupus erythemathosus. The authors consider that these associated diseases could modulate their expression.

A meta-analysis of mortality in rheumatic diseases

IntroductionData reporting mortality in rheumatic diseases vary widely. The objective of this systematic review and meta-analysis of published data is to provide an accurate overview of the current risk of mortality in rheumatic diseases. MethodsSystematic review and meta-analysis of published studies identified by a sensitive search using free text and MeSH synonyms of “mortality” and of “rheumatic diseases”, in general and by specific diagnoses. Eligibility criteria were (1) study population with rheumatoid arthritis, systemic lupus erythemathosus, systemic sclerosis, vasculitis, osteoarthritis, osteoporosis, dermatomyositis, or spondyloarthritis; (2) outcome of interest mortality, reported as an standardized mortality ratio (SMR), or easily calculated from data reported; and (3) cohorts or longitudinal observational studies. Assessment of risk of bias relied on the New Castle-Ottawa scale for cohorts; only moderate to high quality studies were included. Separate meta-SMRs were calculated for specific diagnoses. Heterogeneity was studied with meta-regression. ResultsA total of 32 studies were included, none in spondyloarthritis or osteoarthritis. The overall pooled SMR was 2.03 (95% confidence interval (CI) 1.79–2.29), ranging from 1.36 in psoriatic arthritis to 4.80 in vasculitis. The largest individual overall SMR came from studies on inflammatory diseases, and the specific SMR were very high for infections and pulmonary events. Heterogeneity between studies was large; however, the analysis of such heterogeneity within diseases did not provide any association with the collected variables. ConclusionsBased on our results and on the good quality of the included studies, we can conclude that rheumatic diseases increase in general the risk of death, and especially inflammatory diseases.

356 Pulmonary Arterial Hypertension Associated to Antiphospholipid Syndrome in an Infant

BackgroundAntiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial or venous thrombosis and recurrent fetal loss. It may be primary or in association with an underlying systemic disease, particularly systemic lupus erythemathosus.The diagnostic criteria include vascular thrombosis, complications during pregnancy with recurrent losses, positive titers of anticardiolipin and lupus anticoagulant antibodies.Vascular thrombosis can occur anywhere in the body, including lung vessels. The association of APS with pulmonary arterial hypertension has been estimated between 1.8% and 3.5%.MethodsCase Presentation: We present an 18 month old male boy, who was admitted to our hospital with a history of 3 previous episodes of pneumonia, at arrival with pulse saturation of 69% without oxygen, improving to 100% with oxygen. Pulmonary arterial hypertension was documented with echocardiogram resulting in 100 mm Hg without structural abnormalities. An autoimmune etiology was suspected, resulting with high titers of anticardiolipin (IgG 34.6 mg/dL) and anti-b2 glicoprotein (IgG > 200 mg/dL, IgA 53 mg/dL).ResultsTreatment with acenocumarine, hydroxichloroquine and prednisone was initiated. Nowadays he has evolved with clinical improvement, on its last echocardiogram the pulmonary arterial tension resulted in 65 mm Hg, without evidence of thrombosis.ConclusionsWe report an infant with pulmonary arterial hypertension as the only manifestation of antiphospholipid syndrome, with clinical improvement with anticoagulant and steroid therapy.

A Pediatric Case of Systemic Lupus Erythematosus Developed 10 Years after Cord Blood Transplantation for Juvenile Myelomonocytic Leukemia

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a most powerful immunotherapy for hematological malignancies. However, the impact of immunological disturbances as a result of allo-HSCT is not understood well. We experienced an 11-year-old boy who presented with systemic lupus erythemathosus (SLE) 10 years after unrelated cord blood transplantation of male origin for juvenile myelomonocytic leukemia (JMML) with monosomy 7. Bone marrow examination showed complete remission without monosomy 7. Genetic analysis of peripheral blood revealed mixed chimera with recipient cells consisting of <5% of T cells, 50–60% of B cells, 60–75% of NK cells, 70–80% of macrophages, and 50–60% of granulocytes. Significance of persistent mixed chimera as a cause of SLE is discussed.

P-414 - New psychological meanings for life as attributed by brazilian women with systemic lupus erythemathosus clinically remitted: A qualitative study

Systemic Lupus Erythematosus (SLE) is an autoimmune disease and it preferably affects more women. The state emotional is obviously an important factor in the quality of life of tem. It is important for health professionals to know how these patients reframe their lives during an asymptomatic period of the disease. To discuss life experiences of women with SLE in clinical remission of their disease. Qualitative design conducted with semidirected interviews applied to a intentional sample at a rheumatology outpatient service. The speech presented in the interviews suggest that these patients experience the clinical remission, as a normality phase for their lives and they may perform any activity, which during the active phase of the disease they could not accomplish, giving thus they feature a cure for the disease: “… I keep doing things, but not as fast as before. What did you do ten things in one day, today I … “while still” Ah! I feel normal! I have no problem with lupus! I do not P'ra difference. Normal! “Yet another”. Today I feel good. But I have a problem! I did everything I ever wanted. (…)”. There is certain difficulty in dealing with the possibility of exacerbating disease at any time. Patients with SLE have difficulty in dealing with the phase clinical remission of the disease, to the point of use as coping with the disease ‘Denial’. In this case, the denial is suggested when patients discredit the return of specific clinical lupus.