Clinical Characteristics Of Systemic Lupus Erythematosus Research Articles

Modern clinical and epidemiological characteristic of systemic lupus erythematosus based on the data of the territorial registry

Systemic lupus erythematosus (SLE) is a severe rheumatic disease characterized by polysymptomatic clinical picture. At the present stage, there are no updated epidemiological data due to the low prevalence of the disease. The aim of the study was to examine the current clinical and epidemiological characteristics of patients with systemic lupus erythematosus based on the information contained in the territorial register, analysis of occurrence and symptoms at the early stage of the disease. This study demonstrated the epidemiological and clinical characteristics of SLE from the analysis of 107 cases during the period from 2011 to 2013 and retrospective analysis of the cases for 1980-2013. The epidemiological situation was evaluated based on extensive and intensive indicators using statistical software license. The current SLE prevalence was estimated at 5,59 per 100 000 population in 2013, the incidence between 1994 and 2003 at 0,29 per 100 000 population and between 2004 and 2013 at 0,49, with the peak in 2010 up to 1,35 per 100 000 population. The average absolute growth and growth rate of SLE in the first decade was 0,05% and 0,24%, in the second decade 0,001% and 0,006% respectively, with the female to male ratio being 9:1, mean age of the patients 37,62±11,65 years), and ethnic composition of 87 Slavs and 15 Crimean Tatars. The most common symptoms at the early (polyarthritis, fever, dermatitis) and advanced (polyarthritis, Raynaud's syndrome, carditis, myalgia) stages differed from those specified by American College of Rheumatology (1997). The difference between early and late symptoms of SLE was documented . Based on the data obtained, the division of the disease into clinical subtypes (phenotypes) is proposed.

Evaluation of polymorphic variants in apoptotic genes and their role in susceptibility and clinical progression to systemic lupus erythematosus.

Background Systemic lupus erythematosus (SLE) is an autoimmune disease marked by the disruption of the immune homeostasis. Patients exhibit a wide range of clinical manifestations, and environmental and genetic factors are involved in SLE pathogenesis. Evidence suggests that abnormalities in the cellular and molecular events that coordinate apoptosis may favour the generation of autoantigens involved in autoimmunity. In this way, the apoptotic deregulation may be affected by polymorphic variants in apoptotic-related genes. Methods We analyzed FAS, FASL, BCL-2 and BAX polymorphisms in order to correlate to SLE susceptibility and clinical features. A total of 427 SLE patients from the Hospital de Clínicas de Porto Alegre and 543 controls from southern Brazil were evaluated. Results We observed higher frequencies of the FASL -844CC genotype and -844C allele, as well as of the FASL-844C/IVS2nt-124A haplotype in African-derived SLE patients when compared to controls ( P < 0.001). FASL -844C, which is related to high FasL expression, could contribute to increased apoptosis and to the breakdown of immunological tolerance, favouring autoantibody production and inflammation. On the other hand, the BAX -248GA genotype and the -248A allele , related to low protein expression, were observed as a protective factor against SLE in this same population. The rate of apoptosis and cell death was evaluated in peripheral lymphocytes, and SLE patients presented a higher percentage of dead lymphocytes (CD3+Annexin V+ 7-AAD+) compared to the control group. Conclusion Our data support a role for apoptosis in SLE susceptibility.

MiR-155 Deficiency Ameliorates Autoimmune Inflammation of Systemic Lupus Erythematosus by Targeting S1pr1 in Faslpr/lpr Mice.

MicroRNA-155 (miR-155) was previously found involved in the development of systemic lupus erythematosus (SLE) and other autoimmune diseases and the inflammatory response; however, the detailed mechanism of miR-155 in SLE is not fully understood. To explore the in vivo role of miR-155 in the pathogenesis of SLE, miR-155-deficient Fas(lpr/lpr) (miR-155(-/-)Fas(lpr/lpr)) mice were obtained by crossing miR-155(-/-) and Fas(lpr/lpr) mice. Clinical SLE features such as glomerulonephritis, autoantibody levels, and immune system cell populations were compared between miR-155(-/-)Fas(lpr/lpr) and Fas(lpr/lpr) mice. Microarray analysis, RT-PCR, Western blot, and luciferase reporter gene assay were used to identify the target gene of miR-155. miR-155(-/-)Fas(lpr/lpr) mice showed milder SLE clinical features than did Fas(lpr/lpr)mice. As compared with Fas(lpr/lpr) mice, miR-155(-/-)Fas(lpr/lpr) mice showed less deposition of total IgA, IgM, and IgG and less infiltration of inflammatory cells in the kidney. Moreover, the serum levels of IL-4 and IL-17a, secreted by Th2 and Th17 cells, were lower in miR-155(-/-)Fas(lpr/lpr) than Fas(lpr/lpr) mice; the CD4(+)/CD8(+) T cell ratio was restored in miR-155(-/-)Fas(lpr/lpr) mice as well. Sphingosine-1-phosphate receptor 1 (S1PR1) was found as a new target gene of miR-155 by in vitro and in vivo studies; its expression was decreased in SLE patients and Fas(lpr/lpr) mice. miR-155(-/-)Fas(lpr/lpr) mice are resistant to the development of SLE by the regulation of the target gene S1pr1. miR-155 might be a new target for therapeutic intervention in SLE.

Analysis of clinical characteristics between children and adults with systemic lupus erythematosus

Objective To investigate the differences in clinical characteristics between children and adults with systemic lupus erythematosus(SLE). Methods A retrospective cohort study was performed to investigate the differences in clinical data from 89 children and 120 adults with SLE.Clinical manifestations, laboratory results, renal pathological changes and disease activities of patients from the 2 groups were evaluated. Results The most common clinical manifestations including fever, rash, arthritis, renal damage and anemia were found in both groups.However, the incidences of symptoms such as fever, lymphadenectasis, anemia, renal damage, damage of digestive system and nerve system were higher in children with SLE than those in adult patients, and there were statistical significances (χ2=5.085, P=0.024; χ2=6.027, P=0.014; χ2=4.261, P=0.039; χ2=4.221, P=0.040; χ2=4.566, P=0.033; χ2=4.346, P=0.037, respectively). The positive rate of antibodies against double stranded DNA in serum of children with SLE was higher than that in adults (χ2=1.895, P=0.169). However, the positive rate of antibodies against car-diolipin in serum of children with SLE was lower than that in adults, and there was statistical significance (χ2=4.823, P=0.028). Complement C3 and C4 levels in serum of children with SLE were lower than those in group of adults, and there were statistical significance (χ2=4.221, P=0.040; χ2=7.977, P=0.004, respectively). Class Ⅲ and Ⅳ were commonly observed in classification of renal pathological examinations in both groups.But it was shown that the prevalence of renal damage in children with SLE was higher than that in adult patients, and there was statistical significance (χ2= 4.128, P=0.042). The most common SLE disease activity was identified as moderate in the both groups.However, the score of SLE Disease Activity Index was higher in children with SLE than that in adults, there was statistical significance (t=2.192, P=0.031). Conclusions Differences in clinical characteristics of SLE were found in children and adults.Compared with adults with SLE, children patients were found to show higher prevalence of disease activities, damage of multisystem and renal damage.Therefore, children with SLE need to be diagnosed as early as possible and treated aggressively. Key words: Systemic lupus erythematosus; Clinical characteristics; Child; Adult

Correlation between systemic lupus erythematosus and cytomegalovirus infection detected by different methods.

Human cytomegalovirus (HCMV), a β-herpes virus subfamily member, leads to a lifelong, latent infection in most humans, but the correlation between HCMV infection and systemic lupus erythematosus (SLE) remains controversial. We analyzed the relevance of HCMV infection in SLE by analyzing the peripheral blood leukocytes (PBLs) and serum samples of 60 patients with SLE and 111 healthy individuals. HCMV genes UL55 and UL138 were detected in PBLs by polymerase chain reaction (PCR), and HCMV-specific serum IgG and IgM antibodies were investigated by enzyme-linked immunosorbent assay. The relationship between cellular HCMV infection in PBLs and common clinical indicators of SLE was further explored. Data indicated that the frequency of positive IgG and IgM anti-CMV antibodies was not significantly different in SLE patients and controls. However, compared to the healthy controls, the titers of IgG and IgM anti-CMV antibodies in SLE patients were significantly higher. The detection of cellular HCMV infection showed that almost all subjects were positive for UL138 gene in PBLs, but the positivity for UL55 gene was lower in PBLs. HCMV UL138 detection in PBLs was highly consistent with the frequency of the HCMV-specific IgG test and did not show significant difference in SLE patients and healthy controls. However, compared with that in healthy people, the positivity rate for cellular HCMV UL55 detection was significantly higher in SLE patients (P < 0.001). In addition, cellular HCMV UL55 with positive detection in PBLs was associated with significantly different clinical characteristics of SLE than that with negative detection. In conclusion, our data confirmed that the HCMV infection was related to the development of SLE. Especially, some clinical strains or substrains of HCMV, such as containing the UL55 gene in HCMV's genome, might play a vital role in the development of SLE.

A nationwide study of SLE in Japanese identified subgroups of patients with clear signs patterns and associations between signs and age or sex.

We performed a nationwide study to determine the distributions of the signs and clinical markers of systemic lupus erythematosus (SLE) and identify any patterns in their distributions to allow patient subclassification. We obtained 256,999 patient-year records describing the disease status of SLE patients from 2003 to 2010. Of these, 14,779 involved patients diagnosed within the last year, and 242,220 involved patients being followed up. Along with basic descriptive statistics, we analyzed the effects of sex, age and disease duration on the frequencies of signs in the first year and follow-up years. The patients and major signs were clustered using the Ward method. The female patients were younger at onset. Renal involvement and discoid eczema were more frequent in males, whereas arthritis, photosensitivity and cytopenia were less. Autoantibody production and malar rash were positively associated with young age, and serositis and arthritis were negatively associated. Photosensitivity was positively associated with a long disease duration, and autoantibody production, serositis and cytopenia were negatively associated. The SLE patients were clustered into subgroups, as were the major signs. We identified differences in SLE clinical features according to sex, age and disease duration. Subgroups of SLE patients and the major signs of SLE exist.

AB0410 Non-thromboembolic risk in sle associated antiphospholipid syndrome

ObjectivesAntiphospholipid syndrome (APS) is frequently associated with systemic lupus erythematosus (SLE). In addition to an increased thromboembolic risk, it may alter the disease course of SLE. Our aim was to...

Altered expression of TNFSF4 and TRAF2 mRNAs in peripheral blood mononuclear cells in patients with systemic lupus erythematosus: association with atherosclerotic symptoms and lupus nephritis

This study compares the expression levels of tumor necrosis factor ligand superfamily member 4 (TNFSF4) and TNF-R-associated factor 2 (TRAF2) mRNAs in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE) against healthy controls. The association of SLE disease activity index (SLEDAI) and clinical features of SLE with altered expression levels of TNFSF4 and TRAF2 mRNAs were also evaluated. We used real-time reverse transcription polymerase chain reaction to measure TNFSF4 and TRAF2 mRNAs expression levels in peripheral blood mononuclear cells of 57 SLE patients and 57 healthy controls. The expression level of TNFSF4 mRNA was significantly higher in SLE patients than in the control group. Overexpression of TNFSF4 was correlated with arthritis, atherosclerosis and lupus nephritis. TRAF2 mRNA was underexpressed in PBMCs of SLE patients, and its lower expression was associated with atherosclerosis and lupus nephritis. The altered expression levels of TNFSF4 and TRAF2 mRNAs was significantly correlated with SLEDAI. Our results suggest that changes in the expression levels of TNFSF4 and TRAF2 mRNAs may significantly correlate with the pathogenesis of SLE, the disease activity and different clinical features of lupus, particularly lupus nephritis, atherosclerosis and arthritis.

Association of Systemic Lupus Erythematosus Clinical Features with European Population Genetic Substructure

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with a very varied spectrum of clinical manifestations that could be partly determined by genetic factors. We aimed to determine the relationship between prevalence of 11 clinical features and age of disease onset with European population genetic substructure. Data from 1413 patients of European ancestry recruited in nine countries was tested for association with genotypes of top ancestry informative markers. This analysis was done with logistic regression between phenotypes and genotypes or principal components extracted from them. We used a genetic additive model and adjusted for gender and disease duration. Three clinical features showed association with ancestry informative markers: autoantibody production defined as immunologic disorder (P = 6.8×10−4), oral ulcers (P = 6.9×10−4) and photosensitivity (P = 0.002). Immunologic disorder was associated with genotypes more common in Southern European ancestries, whereas the opposite trend was observed for photosensitivity. Oral ulcers were specifically more common in patients of Spanish and Portuguese self-reported ancestry. These results should be taken into account in future research and suggest new hypotheses and possible underlying mechanisms to be investigated. A first hypothesis linking photosensitivity with variation in skin pigmentation is suggested.

Understanding Systemic Lupus Erythematosus Physiopathology in the Light of Primary Immunodeficiencies

Associations between systemic lupus erythematosus (SLE) and primary immunodeficiencies (PIDs) were analyzed to gain insight into the physiopathology of SLE. Some PIDs have been consistently associated with SLE or lupus-like manifestations: (a) homozygous deficiencies of the early components of the classical complement pathway in the following decreasing order: in C1q, 93% of affected patients developed SLE; in C4, 75%; in C1r/s, 57%; and in C2, up to 25%; (b) female carriers of X-linked chronic granulomatous disease allele; and (c) IgA deficiency, present in around 5% of juvenile SLE. In the first two groups, disturbances of cellular waste-disposal have been proposed as the main mechanisms of pathogenesis. On the other hand and very interestingly, there are PIDs systematically associated with several autoimmune manifestations in which SLE has not been described, such as autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX), and autoimmune lymphoproliferative syndrome (ALPS), suggesting that mechanisms considered as critical players for induction and maintenance of tolerance to autoantigens, such as (1) AIRE-mediated thymic negative selection of lymphocytes, (2) Foxp3+ regulatory T cell-mediated peripheral tolerance, and (3) deletion of auto-reactive lymphocytes by Fas-mediated apoptosis, could not be relevant in SLE physiopathology. The non-description of SLE and neither the most characteristic SLE clinical features among patients with agammaglobulinemia are also interesting observations, which reinforce the essential role of B lymphocytes and antibodies for SLE pathogenesis. Therefore, monogenic PIDs represent unique and not fully explored human models for unraveling components of the conundrum represented by the physiopathology of SLE, a prototypical polygenic disease.

Resolution of SLE-related soft-tissue calcification following haematopoietic stem cell transplantation

Calciphylaxis and calcinosis can both cause severe morbidity and mortality in patients with systemic lupus erythematosus (SLE). Haematopoietic stem cell transplantation (HSCT) has been successfully used to treat patients with refractory SLE. It was hypothesized that in calciphylaxis and calcinosis, ongoing inflammatory activity contributes to the calcium deposition in the media of small arteries, as well as perivascular and periarticular tissues. We report three patients whose soft-tissue calcification syndromes dramatically resolved after undergoing HSCT. Three patients referred for refractory SLE underwent HSCT at a tertiary care medical center. SLE serologies and clinical features before and after HSCT were recorded. Despite receiving >6 months of intravenous cyclophosphamide (CYC), three SLE patients showed signs of persistent lupus activity, including severe soft-tissue calcification. The first patient was on haemodialysis and developed severe calciphylaxis with large ulcers and tissue necrosis. The second patient had calcinosis, with palpable crystals extruding from ulcers. The third patient had calcinosis characterized by subcutaneous nodules and plaques. Because prior conventional therapies had failed, the three were treated with high-dose CYC, anti-thymocyte globulin and HSCT. They have been followed post-HSCT for 26-38 months, with excellent clinical responses, including sustained resolution of skin abnormalities. The successful treatment of advanced calcium deposition by aggressive immune ablation underscores the contribution of SLE-mediated inflammation to soft-tissue calcification syndromes.

HLA-DRB1 alleles in juvenile-onset systemic lupus erythematosus: renal histologic class correlations

Human leukocyte antigens (HLA) DRB1*03 and DRB1*02 have been associated with systemic lupus erythematosus (SLE) in Caucasians and black populations. It has been observed that certain HLA alleles show stronger associations with SLE autoantibodies and clinical subsets, although they have rarely been associated with lupus renal histologic class. In the present study, HLA-DRB1 allele correlations with clinical features, autoantibodies and renal histologic class were analyzed in a cohort of racially mixed Brazilian patients with juvenile-onset SLE. HLA-DRB1 typing was carried out by polymerase chain reaction amplification with sequence-specific primers using genomic DNA from 55 children and adolescents fulfilling at least four of the American College of Rheumatology criteria for SLE. Significance was determined by the chi-square test applied to 2 x 2 tables. The HLA-DRB1*15 allele was most frequent in patients with renal, musculoskeletal, cutaneous, hematologic, cardiac, and neuropsychiatric involvement, as well as in patients positive for anti-dsDNA, anti-Sm, anti-U1-RNP, and anti-SSA/Ro antibodies, although an association between HLA alleles and SLE clinical features and autoantibodies could not be observed. The HLA-DRB1*17, HLA-DRB1*10, HLA-DRB1*15, and HLA-DRB1*07 alleles were significantly higher in patients with renal histologic class I, class IIA, class IIB, and class V, respectively. The present results suggest that the contribution of HLA- DRB1 alleles to juvenile-onset SLE could not be related to clinical or serological subsets of the disease, but it may be related to renal histologic classes, especially class I, class II A, class II B, and class V. The latter correlations have not been observed in literature.

Polymorphisms of toll-like receptor 2 and 4 genes in rheumatoid arthritis and systemic lupus erythematosus.

Human toll-like receptors (TLRs) participate in the innate response and signal the activation of adaptive immunity. Therefore, these TLRs may be important in autoimmune diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). We investigated, by using a polymerase chain reaction restriction-fragment length polymorphism method, the possible association between the polymorphisms of TLR2 (Arg677Trp and Arg753Gln) and TLR4 (Asp299Gly and Thr399Ile) genes with the susceptibility or severity of RA and SLE. Our study population consisted of 122 patients with SLE, 224 patients with RA, and a control group of 199 healthy individuals. The TLR2 polymorphisms were very rare in our population; no individual carrying the TLR2-Arg677Trp polymorphism was observed, whereas the TLR2-Arg753Gln polymorphism was present in only 1% of the total population. We found no statistically significant differences in the TLR4-Asp299Gly and the TLR4-Thr399Ile genotype or allele distribution between SLE patients, RA patients, and control individuals. Similarly, no association was found with any of the demographic and clinical parameters tested either in RA or in SLE patients. In conclusion, a case-control study was used to analyze, for the first time, the influence of TLR2 and TLR4 gene polymorphism on the predisposition and clinical characteristics of SLE and RA but provided no evidence for association of TLR2 or TLR4 gene polymorphism with either disease in the population under study.

Tumor necrosis factor receptor 2 polymorphism in systemic lupus erythematosus: no association with disease

Genetic factors and immune dysregulation play important roles in the development of systemic lupus erythematosus (SLE). Tumor necrosis factor receptor 2 (TNFR2) is suggested to be involved in the development of SLE because its genetic locus (1p36) encompasses one of the susceptible loci for SLE and its ligand (TNF) is associated with SLE. To investigate the role of TNFR2 in the pathogenesis of SLE, 139 Korean patients were genotyped with SLE, 137 healthy control subjects were genotyped for TNFR2 196 R/M polymorphism in exon 6 with PCR-SSCP, and the clinical characteristics of SLE were analyzed according to the genotypes. The genotype frequencies of 196 R/R, 196 R/M, and 196 M/M were 3.6%, 30.9%, and 65.5% in SLE patients and 4.4%, 26.3%, and 69.3% in healthy controls ( p = 0.676). The allelic frequency of 196 R was 19.1% in SLE patients and 17.5% in healthy controls ( p = 0.638, odds ratio = 1.109, and the 95% confidence interval = 0.720–1.708). The clinical characteristics were not different according to the genotypes. In conclusion, no skewed distribution of TNFR2 196 R/M polymorphism was found in Korean patients with SLE compared with healthy controls. Further studies in other populations will be needed to elucidate the role of the TNFR2 polymorphism in the development of SLE.

Immune-complex disease.

THE term immune-complex disease describes a state in which circulating antigen–antibody complexes, formed by coexisting immune reactants, induce vascular injury. In this presentation I will review evidence that immune complexes are responsible for the development of glomerulonephritis in systemic lupus erythematosus (SLE), and analyze the variables affecting the pathogenesis of an experimental model (chronic serum sickness) that, in many respects, resembles SLE nephritis. Systemic Lupus Erythematosus Clinical Features At the outset, it is appropriate to comment on the clinical and pathological features of the syndrome as we now recognize them and to compare them with the picture of SLE 20 . . .