Electrocardiographic and echocardiographic abnormalities in systemic lupus erythematosus : Initial data from Cameroonian patients

Atherosclerosis is an inflammatory disease and the major cause of cardiovascular disease (CVD) in general. Atherosclerotic plaques are characterized by the presence of activated immune competent cells, but antigens and underlying mechanisms causing this immune activation are not well defined. During recent years and with improved treatment of acute disease manifestations, it has become clear that the risk of CVD is very high in a prototypic autoimmune disease, systemic lupus erythematosus (SLE). SLE-related CVD and atherosclerosis are important clinical problems but may in addition also shed light on how immune reactions are related to premature atherosclerosis and atherothrombosis. A combination of traditional and nontraditional risk factors, including dyslipidaemia (and to a varying degree hypertension, diabetes and smoking), inflammation, antiphospholipid antibodies (aPL) and lipid oxidation are related to CVD in SLE. Premature atherosclerosis in some form leading to atherothrombosis is likely to be a major underlying mechanism, though distinctive features if any, of SLE-related atherosclerosis when compared with 'normal' atherosclerosis are not clear. One interesting possibility is that factors such as inflammation or aPL make atherosclerotic lesions in autoimmune disease more prone to rupture than in 'normal' atherosclerosis. Whether premature atherosclerosis is a general feature of SLE or only affects a subgroup of patients remains to be demonstrated. Treatment of SLE patients should also include a close monitoring of traditional risk factors for CVD. In addition, attention should also be paid to nontraditional risk factors such as inflammation and SLE-related factors such as aPL. Hopefully novel therapeutic principles will be developed that target the causes of the inflammation and immune reactions present in atherosclerotic lesions.

Nonstandard and adjunctive medical therapies for systemic lupus erythematosus

PurposeImmune inhibitory receptors are important in maintaining immune homeostasis and preventing autoimmunity. We recently showed that the function of immune inhibitory CD200 Receptor (CD200R) changes in systemic lupus erythematosus (SLE)...

Human γδ T cells recognize conserved endogenous and stress-induced antigens typically associated with autoimmune diseases. However, the role of γδ T cells in autoimmune diseases is not clear. Few autoimmune disease-related antigens recognized by T cell receptor (TCR) γδ have been defined. In this study, we compared Vδ2 TCR complementarity-determining region 3 (CDR3) between systemic lupus erythematosus (SLE) patients and healthy donors. Results show that CDR3 length distribution differed significantly and displayed oligoclonal characteristics in SLE patients when compared with healthy donors. We found no difference in the frequency of Jδ gene fragment usage between these two groups. According to the dominant CDR3δ sequences in SLE patients, synthesized SL2 peptides specifically bound to human renal proximal tubular epithelial cell line HK-2; SL2-Vm, a mutant V sequence of SL2, did not bind. We identified the putative protein ligand chaperonin-containing T-complex protein 1 subunit ζ (CCT6A) using SL2 as a probe in HK-2 cell protein extracts by affinity chromatography and liquid chromatography-electrospray ionization-tandem mass spectrometry analysis. We found CCT6A expression on the surface of HK-2 cells. Cytotoxicity of only Vδ2 γδ T cells to HK-2 cells was blocked by anti-CCT6A antibody. Finally, we note that CCT6A concentration was significantly increased in plasma of SLE and rheumatoid arthritis patients. These data suggest that CCT6A is a novel autoantigen recognized by Vδ2 γδ T cells, which deepens our understanding of mechanisms in autoimmune diseases.

BackgroundSystemic lupus erythematosus (SLE) patients are at an increased risk for infection. It is known that some SLE patients develop severe acute illnesses and require admission to the intensive care...

Excerpt During the last six years the author has had the opportunity personally to study and treat 175 patients with systemic lupus erythematosus. The purpose of this paper is to review the current...

A study of cardiovascular manifestations in systematic lupus erythematosus in upper assam

Although autopsy studies have documented that heart is affected in most of systemic lupus erythematosus (SLE) patients, clinical manifestations occur in less than 10%. QT dispersion, a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function, has not been studied in SLE patients. The aim of our study was to evaluate the QT dispersion (QTd) in SLE patients without overt cardiac involvement. Eighty-three patients with a diagnosis of SLE (mean age 41+/-13) and age- and sex-matched 77 healthy control subjects (mean age 43+/-10) were enrolled in the study. All subjects had their complete history taken, laboratory examination, and transthoracic echocardiography (ECG). Patients with cardiac disease, hypertension, diabetes, or taking medications that may effect QTd or any ECG abnormalities were excluded. Resting 12-lead ECG were recorded for measurement of QTd. None of the patients and control subjects had overt cardiac involvement. The mean SLE duration was 86.5+/-15.4 months. QT dispersion was significantly greater in SLE patients than incontrol subjects (55.2+/-24.7 vs 20.7+/-5.3 ms, respectively; p<0.001). There was no correlation between QTd and duration of SLE, SLEDAI-K score, corticosteroid usage, and presence of anti SS-A antibody. QT dispersion is significantly increased in SLE patients without overt cardiac involvement. Our result suggests that prolonged QT dispersion can be a useful noninvasive and simple method for early detection of cardiac involvement in SLE patients.

A Clinical Electrophysiological Study of Emotional Lability in Patients With Systemic Lupus Erythematosus

Objectives: This study was to evaluate the incidence and ocular manifestation in systemic lupus erythematosus (SLE) patients.&#x0D; Methods: A total of 50 cases with age group 15 to 50 years were enrolled. A detail history, clinical examinations and relevant investigations were performed to all cases. Patients who were diagnosed with systemic lupus erythamatusus (SLE) by using American Rheumatologic criteria with or without ocular features were included in this study.&#x0D; Results: Data was analysed by using simple statistical methods with the help of MS-office software. All data was tabulated and percentage was calculated.&#x0D; Conclusions: Females were commonly suffered with systemic lupus erythamatusus (SLE) and it was commonly seen in age 15-25 years. Episcleritis was the most common symptoms in SLE. Second most common symptoms were conjunctivitis and scleritis. Right eye was more affected than left eye. Most of the cases had ANA positive. Hence, ocular manifestation is the most common in SLE patients. Early diagnosis and prompt treatment may give light of hope for SLE patients. And more research is needed in order to determine which therapy will provide the best prevention and management in SLE patients.&#x0D; Key words: Systemic lupus erythamatusus (SLE), ocular manifestation, age group, ANA-positive.

To investigate the association of angiotensin-converting enzyme (ACE) gene polymorphism and serum ACE level among Egyptian SLE patients and its relation to disease activity parameters. We enrolled 50 Egyptian female systemic lupus erythematosus (SLE) patients and 29 healthy controls. Measurement of serum ACE level was done using ELISA, and the ACE genotype was determined by polymerase chain reaction using genomic DNA from peripheral blood. A significant difference was found in ACE genotypes between SLE patients and controls (χ(2 )= 7.84, p = 0.02). The frequency of ACE DD versus (DI and II) genotypes was significantly higher in SLE patients compared with controls (χ(2 )= 5.57, p = 0.018 and OR for risk of SLE was 3.1 with 95% confidence interval: 1.198.06). Mean serum ACE level was significantly higher in the SLE group compared with controls (p = 0.006). Subjects with DD genotype had a significantly higher mean level than those with DI (p = 0.015) and II genotypes (p = 0.02). Lupus nephritis patients had a significantly higher frequency of DD versus DI and II genotypes compared with lupus patients without nephritis (Fisher's exact test, p = 0.025) and controls (χ (2) =8.74, p = 0.003). SLE patients with vasculopathy had a significantly higher frequency of DD versus DI/II genotypes compared with SLE patients without vasculopathy (Fisher's exact test, p = 0.04) and controls (χ(2 )= 9.84 and p = 0.002). Mean serum ACE level was significantly higher in the lupus nephritis and SLE patients with vasculopathy compared with controls (p = 0.008, p = 0.001, respectively). Significant positive correlations were found between serum ACE level and serum creatinine and 24 h proteinuria (p = 0.03, 0.009, respectively). SLE patients with DD genotype had a statistically significant higher mean SLEDAI score than those with (DI/II) genotypes (p = 0.02). Significant positive correlation was found between serum ACE levels and SLEDAI scores (p = 0.04). ACE genotype and subsequently serum ACE level could be associated with the disease activity of Egyptian SLE patients; in addition, ACE deletion polymorphism might be used as one of the predictive factors for the activity of SLE. Further studies on a larger number of patients should be done to determine the exact prevalence of ACE gene polymorphism among Egyptian SLE patients.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with numerous abnormalities recorded at the cellular, molecular, and genetic level. Expression of the basic leucine zipper transcription factor cAMP-responsive element modulator (CREM)α was reported to be abnormally increased in T cells from SLE patients. CREMα suppresses IL-2 and T cell receptor ζ chain gene transcription by direct binding to the respective promoters. Here, we show that increased CREM expression is the result of enhanced promoter activity. DNA binding analyses reveal direct binding of transcription factor specificity protein-1 (SP-1) to the CREM promoter resulting in enhanced transcriptional activity and increased CREM expression. Protein phosphatase 2A is known to activate SP-1 through dephosphorylation at its serine residue 59. Our results show that nuclei from SLE T cells contain lower levels of Ser(59)-phosphorylated SP-1 protein and a stronger SP-1 binding to the CREM promoter. We conclude that protein phosphatase 2A accounts for enhanced SP-1 dephosphorylation at Ser(59) in SLE T cells. More importantly, CREM promoter activity mirrors reliably disease activity in SLE patients, underscoring its potential role as a biomarker for the prediction of flares in SLE patients.

Objective. To evaluate the prevalence of traditional risk factors in systemic lupus erythematosus (SLE) patients, assess the 10-years risk of developing type 2 diabetes mellitus (DM) in SLE patients and identify those necessitating preventive interventions following altered glucose metabolism using the Finnish Type 2 Diabetes Risk Score (FINDRISK) questionnaire.Materials and methods. The study included 119 SLE patients (107 women, 12 men, with median age 39 [33; 47] years and mean disease duration 6 [1,12] years.The control group included 100 age and sex matched individuals without immune-mediated inflammatory rheumatic diseases and without previous DM history. The 10-years risk of developing type 2 DM in SLE patients and the controls assessed using the Russian adaptation of Finnish Type 2 Diabetes Risk Score questionnaire. Fasting glucose levels in venous blood were measured in all SLE patients. Glucose levels ≥6.1 mmol/L were interpreted as fasting hyperglycemia.Results. The prevalence of traditional type 2 DM risk factors in SLE patients was as follows: abdominal obesity was found in 63.9%, lack of physical activity – in 62.2%, intake of antihypertensive drugs— in 52.9%, BMI ≥25 kg/m2 in 42.0%, unhealthy diets – in 40.3%, family history of DM – in 35.3%, age over 45 years – in 32.8%, history of hyperglycemia episodes – in 15.1%. Abdominal obesity and intake of antihypertensive drugs were more often documented in SLE patients, while all other risk factors were equally represented in SLE and control groups. On average 3 [2; 5] risk factors were found in each SLE patient. Low type 2 DM risk was a more rare phenomenon in SLE patients vs healthy controls (36.1 and 51%, р&lt;0.05). Primary type 2 DM prophylaxis recommended in case of moderate, high and very high risk was more often indicated in SLE vs the healthy controls (29.4 and 17.0%, р=0.03), including those younger than 45 years (18.3 and 6.1% respectively, р=0.05). Fasting hyperglycemia was found in 1.2% patients with low-slightly increased type 2 DM risk and in 16.1% individuals with moderate, high and very high risk (p=0.04).Conclusions. High prevalence of such traditional type 2 DM risk factors as abdominal obesity, lack of physical activity and intake of antihypertensive drugs was demonstrated in SLE patients. Finnish Type 2 Diabetes Risk Score questionnaire identified moderate, high and very high 10-year risk of developing type 2DM in 29.4% SLE patients, necessitating prophylactic interventions in view of altered glucose metabolism.

Objective: To evaluate the volumetric brain magnetic resonance imaging (MRI) findings in a population‐based sample of systemic lupus erythematosus (SLE) patients and to detect a possible relationship between cerebral MRI abnormalities and specific neuropsychiatric (NP) manifestations.Methods: The study population consisted of patients with SLE (n = 43) in Pirkanmaa Health Care District, Finland and of a sex‐ and age‐stratified reference group from the general population (n = 43). In addition to a clinical neurological investigation, all subjects received a detailed neuropsychological assessment and an MRI study. Volumetric measures of cerebral atrophy as well as T1‐ and T2‐weighted lesions were obtained. SLE activity was assessed by the European Consensus Lupus Activity Measure (ECLAM) index, and accumulated NP abnormalities were measured by the Systemic Lupus International Collaborating Clinics (SLICC) damage index. A cumulative lifetime dose of glucocorticoids was determined from the patientrecords.Results: Compared with controls, SLE patients had increased volumes of both T1‐ and T2‐weighted lesions (p = 0.019 and p<0.0001, respectively) and increased cerebral atrophy (p<0.001). All the measured MRI parameters were statistically significantly higher in NPSLE than in non‐NPSLE patients. In SLE patients, cerebral atrophy was associated with cognitive dysfunction, epileptic seizures, and cerebrovascular disease; T1‐weighted lesions were associated with epileptic seizures and T2‐weighted lesions with cognitive dysfunction. All MRI parameters correlated significantly with the SLICC index but not with the ECLAM index. A positive correlation was found between a cumulative dose of glucocorticoids and cerebral atrophy in SLE patients.Conclusion: MRI abnormalities, including brain atrophy and T1‐ and T2‐weighted lesions, are significantly more common in patients with SLE than in the general population and they are related to specific NP manifestations. Our findings also provide support for the organic aetiology of cognitive dysfunction in SLE.

Objective To investigate the function of megakaryocytic cells in systemic lupus erythematosus(SLE)patients with thrombocytopenia. Methods Standard hematological tests，bone marrow examinations and immunological tests were carried out to scan thrombocytopenia in a total of 176 consecutive SLE patients，the clinical and laboratory data were compared between SLE patients with or without thrombocytopenia，and bone marrow examinations for analysis of megakaryocytic function in SLE patients with thrombocytopenia were compared with that in 32 SLE patients without thrombocytopenia. Results Thrombocytopenia was identified in 64 SLE patients(36.4%)，among whom，48(75%)with mild thrombocytopenia and 16(25%)with severe thrombocytopenia. In comparison with patients without thrombocytopenia，SLE patients with thrombocytopenia had higher incidence of serositis，more sever renal damage，lower serum C3 levels(P<0.05)，and higher disease activity scores(P<0.05). The total numbers of megakaryocytes was decreased in SLE patients with thrombocytopenia in comparision with that in SLE patients without thrombocytopenia(P=0.001)，especially the platelete-forming megakaryocyte. Whereas，the numbers of promegakaryocytes was markedly increased in SLE patients with thrombocytopenia(P=0.019). Conclusions Thrombocytopenia in SLE is more likely developed in patients with active and severe disease. Impaired function in megakaryocytic proliferation and differentiation may contribute to the thrombocytopenia occurred in SLE patients.