lncRNA MALAT-1 Predicts Prognosis of Patients with Systemic Lupus Erythematosus

Abstract Objective To evaluate the association of MALAT-1 and the prognosis of patients with systemic lupus erythematosus (SLE). Materials and Methods A total of 87 SLE patients and 50 healthy controls were recruited. The expression levels of MALAT-1 were measured by quantitative PCR at baseline. Multivariate Cox regression analysis was performed to assess the association of MALAT-1 levels with survival after adjusting for potential confounding factors. Results The MALAT-1 levels in patients with SLE were significantly higher compared with healthy controls (p<0.01). The 10-year survival of patients with a higher MALAT-1 level was significantly lower than that of patients with a lower MALAT-1 level (HR=5.54; 95% CI: 1.49–20.55; p=0.01). Multivariate Cox regression indicated that the MALAT-1 level was significantly associated with a risk of mortality (HR=10.02, 95% CI: 1.14–88.14, p=0.04). Conclusion The expression levels of MALAT-1 may be a promising biomarker for evaluating the prognosis of SLE patients.

Download Full-text

The decreased expression of IKBKE in systemic lupus erythematosus

Clinical Rheumatology ◽

10.1007/s10067-020-05006-6 ◽

2020 ◽

Vol 39 (9) ◽

pp. 2611-2617

Author(s):

Tingting Zhu ◽

Jiaqi Hong ◽

Zongwen Shuai ◽

Shengqian Xu ◽

Danfeng Qian ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Clinical Characteristics ◽

Regulatory Function ◽

Healthy Controls ◽

Systemic Lupus ◽

Expression Levels ◽

Lower Expression ◽

Mrna Expression Levels

Abstract Objective The IKBKE has been proven to be associated with systemic lupus erythematosus (SLE) in a genome-wide association study (GWAS) conducted by our group. The objective of the recent study is to investigate the contribution of IKBKE functional variants (rs2297550) to SLE. Methods We detected the regulatory effect of rs2297550 on IKBKE expression by expression quantitative trait loci (eQTL) study. Then, we investigated the differences of IKBKE mRNA expression levels in peripheral blood mononuclear cells (PBMCs) between 135 SLE patients and 130 healthy controls using quantitative real-time PCR (qRT-PCR). We further analyzed the association of SLE clinical characteristics with IKBKE mRNA expression and rs2297550 polymorphisms. Results The results of eQTL indicated the genotype “GG” of single-nucleotide polymorphism (SNP) rs2297550 was associated with lower expression levels of IKBKE (P = 0.022) in normal controls. Compared with the healthy control group, the expression levels of IKBKE mRNA in patients with SLE were significantly decreased (P = 2.32 × 10−12). In clinical characteristics, we found that IKBKE mRNA expression levels were associated with vasculitis (P = 0.015) and increased C-reactive protein (CRP) (P = 0.021) in SLE patients. Conclusion In this study, we not only detected that the variant rs2297550 of IKBKE may be closely related to SLE, but also proposed functional hypotheses for the association signals. Key Points• The rs2297550 is located in a region with transcriptional regulatory function and may regulate the expression of IKBKE via these regulatory elements.• The genotype “GG” of SNP rs2297550 was associated with lower expression levels of IKBKE.• The expression of IKBKE mRNA was decreased in SLE patients compared with healthy controls.• IKBKE contributes to the clinical characteristics of SLE.

Download Full-text

Seroconversion to antinuclear antibody negativity and its association with disease flare in patients with systemic lupus erythematosus

Lupus ◽

10.1177/0961203320917748 ◽

2020 ◽

Vol 29 (7) ◽

pp. 697-704 ◽

Cited By ~ 1

Author(s):

Oh Chan Kwon ◽

Yong-Gil Kim ◽

Jung Hwan Park ◽

Min-Chan Park

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Antinuclear Antibody ◽

Antinuclear Antibodies ◽

Cox Regression ◽

British Isles ◽

Systemic Lupus ◽

Free Survival ◽

Cox Regression Analysis ◽

Kaplan Meier

Objective To evaluate the rate of seroconversion to antinuclear-antibody negativity in patients with systemic lupus erythematosus and its association with subsequent systemic lupus erythematosus flare risk. Methods Medical records of patients with systemic lupus erythematosus with positive antinuclear antibodies (titer ≥1 : 40) at diagnosis and at least one repeat antinuclear antibody test were reviewed. We determined the frequency of seroconversion to antinuclear antibody negativity among these patients and investigated whether seroconversion to antinuclear antibody negativity was associated with subsequent systemic lupus erythematosus flare risk. The seroconversion to antinuclear antibody negativity was defined as a conversion of positive antinuclear antibodies to a titer below the cut-off of 1 : 40. Systemic lupus erythematosus flare was defined as one new British Isles Lupus Assessment Group A or two new British Isles Lupus Assessment Group B domain scores. To estimate hazard ratios and 95% confidence intervals for systemic lupus erythematosus flare according to seroconversion to antinuclear antibody negativity, Cox regression analysis with adjustment for known systemic lupus erythematosus flare risk factors was performed. Kaplan-Meier analysis was used to compare flare-free survival rates between negative converters and non-converters. Results Among the total 175 patients, seroconversion to antinuclear antibody negativity was found in 17 (9.7%) patients in a median 53.5 (range: 25.7–84.0) months. After the last antinuclear antibody tests, 53 systemic lupus erythematosus flare cases were identified during 14.3 (range: 8.2–21.7) months of follow-up. Systemic lupus erythematosus flare risk was significantly lower in patients with negatively seroconverted antinuclear antibodies (adjusted hazard ratio 0.13, 95% confidence interval 0.03–0.58, p = 0.007). Kaplan-Meier analysis showed significantly higher flare-free survival in negative converters than in non-converters ( p = 0.004). Conclusion Seroconversion to antinuclear antibody negativity occurred in 9.7% of patients over 53.5 months and was associated with a lower future systemic lupus erythematosus flare risk.

Download Full-text

Prognostic Indicators of Hospitalized Patients with Systemic Lupus Erythematosus: A Large Retrospective Multicenter Study in China

The Journal of Rheumatology ◽

10.3899/jrheum.101088 ◽

2011 ◽

Vol 38 (7) ◽

pp. 1289-1295 ◽

Cited By ~ 27

Author(s):

XUEBING FENG ◽

YAOHONG ZOU ◽

WENYOU PAN ◽

XIANGDANG WANG ◽

MIN WU ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Cox Regression ◽

Disease Onset ◽

Antimalarial Drugs ◽

Hospitalized Patients ◽

Systemic Lupus ◽

Female Ratio ◽

Cox Regression Analysis ◽

Factors Associated

Objective.To investigate the mortality of hospitalized patients with systemic lupus erythematosus (SLE) and determine the influential factors associated with poor prognosis.Methods.Medical records of 1956 SLE inpatients from 15 hospitals during the period January 1, 1999, to December 31, 2009, were reviewed. All patients were followed up in January 2010. Potential factors associated with mortality were analyzed, comparing patients who were living with those who were deceased. The independency of those factors significantly related to death was determined by Cox regression analysis.Results.Male to female ratio was 1:15 in this cohort; median age at disease onset was 30 years. Hematologic (70.0%), mucocutaneous (68.2%), musculoskeletal (57.9%), and renal (48.7%) involvements were most often seen in these patients at time of admission. The overall mortality was 8.5% (n = 166), with infection (25.9%), renal failure (19.3%), and neuropsychiatric lupus (18.7%) the leading 3 causes of death. Independent predictors for mortality in this cohort of SLE patients were neuropsychiatric involvement [hazard ratio (HR) 2.19], anemia (HR 1.69), SLEDAI score > 8 at discharge (HR 1.64), increased serum creatinine (HR 1.57), low serum albumin (HR 1.56), cardiopulmonary involvement (HR 1.55), and patient untreated before admission (HR 1.48), whereas the use of antimalarial drugs (HR 0.62) and positive anti-Sm antibody (HR 0.60) were shown to be protective factors.Conclusion.SLE patients with delayed treatment and refractory disease have poorer prognosis. A high incidence of death would be expected if they have neuropsychiatric involvement, anemia, azotemia, or cardiopulmonary involvement. Combination therapy with antimalarial drugs may provide some benefit to patients with SLE.

Download Full-text

Ultrasensitive serum interferon-α quantification during SLE remission identifies patients at risk for relapse

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2019-215571 ◽

2019 ◽

Vol 78 (12) ◽

pp. 1669-1676 ◽

Cited By ~ 9

Author(s):

Alexis Mathian ◽

Suzanne Mouries-Martin ◽

Karim Dorgham ◽

Hervé Devilliers ◽

Hans Yssel ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

Single Molecule ◽

Lupus Erythematosus ◽

Cox Regression ◽

Activity Index ◽

Serum Levels ◽

Interferon Α ◽

Systemic Lupus ◽

Cox Regression Analysis ◽

Time To Relapse

ObjectivesMaintenance of remission has become central in the management of systemic lupus erythematosus (SLE). The importance of interferon-alpha (IFN-α) in the pathogenesis of SLE notwithstanding, its expression in remission has been poorly studied as yet. To study its expression in remission and its prognostic value in the prediction of a disease relapse, serum IFN-α levels were determined using an ultrasensitive single-molecule array digital immunoassay which enables the measurement of cytokines at physiological concentrations.MethodsA total of 254 SLE patients in remission, according to the Definition of Remission in SLE classification, were included in the study. Serum IFN-α concentrations were determined at baseline and patients were followed up for 1 year. Lupus flares were defined according to the Safety of Estrogens in Lupus Erythematosus: National Assessment version of the Systemic Lupus Erythematosus Disease Activity Index Flare Index, whereas the Kaplan-Meier analysis and Cox regression analysis were used to estimate the time to relapse and to identify baseline factors associated with time to relapse, respectively.ResultsOf all patients in remission, 26% displayed abnormally high IFN-α serum levels that were associated with the presence of antibodies specific for ribonucleoprotein (RNP), double stranded (ds)DNA and Ro/SSA60, as well as young age. Importantly, elevated-baseline IFN-α serum levels and remission duration were associated in an independent fashion, with shorter time to relapse, while low serum levels of complement component 3 and anti-dsDNA Abs were not.ConclusionDirect serum IFN-α assessment with highly sensitive digital immunoassay permits clinicians to identify a subgroup of SLE patients, clinically in remission, but at higher risk of relapse.

Download Full-text

Prevalence, risk factors, and impact on mortality of neuropsychiatric lupus: a prospective, single-center study

Lupus ◽

10.1177/0961203318772021 ◽

2018 ◽

Vol 27 (8) ◽

pp. 1338-1347 ◽

Cited By ~ 17

Author(s):

G Y Ahn ◽

D Kim ◽

S Won ◽

S T Song ◽

H-J Jeong ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Logistic Regression ◽

Regression Analysis ◽

Lupus Erythematosus ◽

Antiphospholipid Antibody ◽

Systemic Lupus ◽

Multivariable Logistic Regression ◽

Risk Of Mortality ◽

Antibody Positivity

Objective The objective of this paper is to identify the prevalence, risk factors, and impact on mortality of neuropsychiatric systemic lupus erythematosus (NPSLE). Methods Patients from the Hanyang BAE lupus cohort were registered and followed from 1998 to 2015. NPSLE was defined using American College of Rheumatology (ACR) case definitions and Ainiala criteria. Demographics, autoantibodies, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and Systemic Lupus International Collaborating Clinic (SLICC)/ACR Damage Index were collected at baseline and then annually. Mortality data were derived by linking data from the Korean National Statistics Office. Multivariable logistic regression and Cox regression analysis were conducted in the inception cohort to assess the risk factors and mortality impact of NPSLE. Results Of 1121 registered patients, 429 (38.3%) had NPSLE manifestations according to ACR criteria and 216 (19.3%) by Ainiala criteria. In multivariable logistic regression analysis, higher SLEDAI (OR 1.08, CI 1.01–1.16, p = 0.02) and antiphospholipid antibody positivity (OR 1.72, CI 1.03–2.87, p = 0.04) at SLE diagnosis increased NPSLE risk, while elevated anti-dsDNA antibodies (OR 0.43, CI 0.24–0.78, p < 0.01) and greater education duration (OR 0.92, CI 0.85–1.00, p = 0.04) showed reduced risk of NPSLE. Cox proportional hazard models demonstrated that presence of NPSLE had a three-fold increased risk of mortality (HR 3.09, CI 1.03–9.21, p = 0.04), especially in patients with focal CNS NPSLE (HR = 7.83, CI 2.12–28.96, p < 0.01). Conclusion Higher SLEDAI, antiphospholipid antibody positivity, absence of anti-dsDNA antibody at SLE diagnosis, and fewer years of education are risk factors for development of NPSLE. Presence of NPSLE, especially focal CNS NPSLE, increased the risk of mortality in SLE patients.

Download Full-text

Which patients with systemic lupus erythematosus in remission can withdraw low dose steroids? Results from a single inception cohort study

Lupus ◽

10.1177/09612033211002269 ◽

2021 ◽

Vol 30 (6) ◽

pp. 991-997

Author(s):

Serena Fasano ◽

Melania Alessia Coscia ◽

Luciana Pierro ◽

Francesco Ciccia

Keyword(s):

Systemic Lupus Erythematosus ◽

Lupus Erythematosus ◽

Low Dose ◽

Cox Regression ◽

Systemic Lupus ◽

Cox Regression Analysis ◽

History Of ◽

Risk Of Disease ◽

Flare Index ◽

Maintenance Group

Background A progressive tapering until withdrawal of glucocorticoids (GC) is considered one of the main goals of Systemic Lupus Erythematosus (SLE) management. However, which patient may be a candidate for safe GC withdrawal has not been determined yet. This study aimed to evaluate the rate of low-dose GC withdrawal in SLE patients in remission and to identify predictors of flares. Methods Eligible patients were SLE patients in prolonged clinical remission defined by a cSLEDAI = 0 for at least 2 years and on a stable SLE treatment (including daily 5 mg prednisone). Flares were defined by SELENA-SLEDAI Flare Index. Predictors of flares after GC withdrawal were analyzed by Cox regression. Results We selected 56 patients in whom a GC withdrawal was attempted. 98 patients were in the prednisone maintenance group. The proportion of patients experiencing a flare was not significantly lower in the maintenance group than in the withdrawal group (p = 0.81). However, among the withdrawal group, the rate of flares was significantly higher in serologically active clinically quiescent (SACQ) patients (p < 0,0001). At Cox regression analysis, duration of hydroxychloroquine (HCQ) therapy and ≥5 year remission at withdrawal were protective factors, while a SACQ disease and history of lupus nephritis increased the risk of disease flare. Conclusion GC withdrawal is an achievable target in SLE and may be attempted in patients in complete remission.However, it might underline a caution in patients with SACQ disease who may be at greater risk forflare when GCare discontinued. HCQ therapy and durable remission can significantly reduce the risk.

Download Full-text

Predictors of renal damage in systemic lupus erythematous patients: data from a multiethnic, multinational Latin American lupus cohort (GLADEL)

RMD Open ◽

10.1136/rmdopen-2020-001299 ◽

2020 ◽

Vol 6 (3) ◽

pp. e001299

Author(s):

Cristina Reátegui-Sokolova ◽

Manuel F Ugarte-Gil ◽

Guillermina B Harvey ◽

Daniel Wojdyla ◽

Guillermo J Pons-Estel ◽

...

Keyword(s):

Risk Factors ◽

Systemic Lupus Erythematosus ◽

Latin American ◽

Lupus Erythematosus ◽

Renal Damage ◽

Cox Regression ◽

Damage Index ◽

Early Response ◽

Male Gender ◽

Systemic Lupus

AimA decrease in proteinuria has been considered protective from renal damage in lupus nephritis (LN), but a cut-off point has yet to be established. The aim of this study was to identify the predictors of renal damage in patients with LN and to determine the best cut-off point for a decrease in proteinuria.MethodsWe included patients with LN defined clinically or histologically. Possible predictors of renal damage at the time of LN diagnosis were examined: proteinuria, low complement, anti-double-stranded DNA antibodies, red cell casts, creatinine level, hypertension, renal activity (assessed by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)), prednisone dose, immunosuppressive drugs and antimalarial use. Sociodemographic variables were included at baseline. Proteinuria was assessed at baseline and at 12 months, to determine if early response (proteinuria <0.8 g/day within 12 months since LN diagnosis) is protective of renal damage occurrence. Renal damage was defined as an increase of one or more points in the renal domain of The Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index (SDI). Cox regression models using a backward selection method were performed.ResultsFive hundred and two patients with systemic lupus erythematosus patients were included; 120 patients (23.9%) accrued renal damage during their follow-up. Early response to treatment (HR=0.58), antimalarial use (HR=0.54) and a high SES (HR=0.25) were protective of renal damage occurrence, whereas male gender (HR=1.83), hypertension (HR=1.86) and the renal component of the SLEDAI (HR=2.02) were risk factors for its occurrence.ConclusionsEarly response, antimalarial use and high SES were protective of renal damage, while male gender, hypertension and higher renal activity were risk factors for its occurrence in patients with LN.

Download Full-text

Tim-3 associated with apoptotic NK cells and disease activity in SLE

European Journal of Inflammation ◽

10.1177/20587392211000570 ◽

2021 ◽

Vol 19 ◽

pp. 205873922110005

Author(s):

Di Zhao ◽

Xiao Yang ◽

Jie Zhang ◽

Yi Zhang

Keyword(s):

Systemic Lupus Erythematosus ◽

Flow Cytometry ◽

T Cell ◽

Disease Activity ◽

Nk Cells ◽

Lupus Erythematosus ◽

Healthy Controls ◽

Systemic Lupus ◽

Potential Target

T cell immunoglobulin and mucin domain-containing molecule-3 (Tim-3) has been found to play important roles in systemic lupus erythematosus (SLE), however, whether Tim-3 is involved in apoptosis of NK cells in SLE remains unknown. The proportion of CD3−CD56+ NK cells and the percentage of AnnexinV+ NK cells were analyzed by flow cytometry in SLE patients and healthy controls. Tim-3 expression on NK cells was also evaluated by flow cytometry. We firstly observed a decreased proportion of NK cells and an increased proportion of apoptotic NK cells in SLE patients. The proportion of apoptotic NK cells was positively correlated with anti-dsDNA and SLEDAI. Tim-3 expression on NK cells was up-regulated in SLE patients. Further analysis showed that Tim-3 expression on NK cells was negatively correlated with the proportion of apoptotic NK cells, anti-dsDNA and SLEDAI, while positively correlated with the proportion of NK cells. The present results suggest that Tim-3 might play roles in SLE by regulating the apoptosis of NK cells and Tim-3 might serve as a potential target for the treatment of SLE.

Download Full-text

Elevated levels of IL-24 in systemic lupus erythematosus patients

Lupus ◽

10.1177/0961203319845476 ◽

2019 ◽

Vol 28 (6) ◽

pp. 748-754 ◽

Cited By ~ 1

Author(s):

R C Li ◽

J Guo ◽

L C Su ◽

A F Huang

Keyword(s):

Systemic Lupus Erythematosus ◽

Disease Activity ◽

Lupus Erythematosus ◽

Inflammatory Cytokine ◽

Activity Index ◽

Clinical Manifestations ◽

Mrna Levels ◽

Healthy Controls ◽

Systemic Lupus ◽

Good Ability

Objective This study aimed to assess IL-24 levels and their association with clinical manifestations in patients with systemic lupus erythematosus (SLE). Methods There were 75 patients with SLE and 58 healthy controls recruited in this study. Serum levels of IL-24 were measured by enzyme-linked immunosorbent assays, and mRNA levels of IL-24 were tested by quantitative real-time polymerase chain reaction . The area under the curve of the receiver operating characteristic (ROC) curve was used for diagnostic ability of the inflammatory cytokine. Results Serum IL-24 levels were significantly higher in SLE patients than that in healthy controls. SLE patients with nephritis had higher IL-24 levels than those without nephritis. Active SLE patients showed higher expression of IL-24 as compared to less active disease patients. The mRNA levels of IL-24 were much higher in SLE patients. Correlation analysis showed significant correlation between serum IL-24 levels and SLE disease activity index. In addition, ROC analysis may suggest good ability of serum IL-24 in differentiating SLE. Conclusion The inflammatory cytokine correlated with SLE disease activity, and may be involved in this disease pathogenesis.

Download Full-text

mRNA expression analysis confirms CD44 splicing impairment in systemic lupus erythematosus patients

Lupus ◽

10.1177/09612033211004725 ◽

2021 ◽

pp. 096120332110047

Author(s):

Andrea Latini ◽

Lucia Novelli ◽

Fulvia Ceccarelli ◽

Cristiana Barbati ◽

Carlo Perricone ◽

...

Keyword(s):

Systemic Lupus Erythematosus ◽

T Cells ◽

Mrna Expression ◽

Lupus Erythematosus ◽

Mononuclear Cells ◽

Direct Sequencing ◽

Healthy Controls ◽

Systemic Lupus ◽

Peripheral Tissues ◽

Variant Isoforms

Background Systemic Lupus Erythematosus (SLE) is a complex chronic autoimmune disease characterized by several immunological alterations. T cells have a peculiar role in SLE pathogenesis, moving from the bloodstream to the peripheral tissues, causing organ damage. This process is possible for their increased adherence and migration capacity mediated by adhesion molecules, such as CD44. Ten different variant isoforms of this molecule have been described, and two of them, CD44v3 and CD44v6 have been found to be increased on SLE T cells compared to healthy controls, being proposed as biomarkers of disease and disease activity. The process of alternative splicing of CD44 transcripts is not fully understood. We investigated the mRNA expression of CD44v3 and CD44v6 and also analyzed possible CD44 splicing regulators (ESRP1 molecule and rs9666607 CD44 polymorphism) in a cohort of SLE patients compared to healthy controls. Methods This study involved 18 SLE patients and 18 healthy controls. Total RNA and DNA were extracted by peripheral blood mononuclear cells. The expression study was conducted by quantitative RT-polymerase chain reaction, using SYBR Green protocol. Genotyping of rs9666607 SNP was performed by direct sequencing. Results CD44v6 mRNA expression was higher in SLE patients compared to healthy controls (p = 0.028). CD44v3/v6 mRNA ratio in healthy controls was strongly unbalanced towards isoform v3 compared to SLE patients (p = 0.002) and decreased progressively from healthy controls to the SLE patients in remission and those with active disease (p = 0.015). The expression levels of CD44v3 and CD44v6 mRNA correlated with the disease duration (p = 0.038, Pearson r = 0.493 and p = 0.038, Pearson r = 0.495, respectively). Splicing regulator ESRP1 expression positively correlated with CD44v6 expression in healthy controls (p = 0.02, Pearson r = 0.532) but not in SLE patients. The variant A allele of rs9666607 of CD44 was associated with higher level of global CD44 mRNA (p = 0.04) but not with the variant isoforms. Conclusions In SLE patients, the increase in CD44v6 protein correlates with a higher transcript level of this isoform, confirming an impairment of CD44 splicing in the disease, whose regulatory mechanisms require further investigation.

Download Full-text