Lupus最新文献

IntroductionJuvenile Systemic Lupus Erythematosus (jSLE) is a rare pediatric rheumatic disease characterized by systemic inflammation that can lead to organ damage. Compared to adults, it often has a more severe course in children. Both disease activity and treatments may result in temporary or permanent damage.ObjectivesTo evaluate risk factors associated with damage occurrence in patients with jSLE.MethodsThis multicenter, retrospective study included patients with jSLE followed for at least 12 months. Low-dose corticosteroid therapy was defined as prednisolone 0.01-0.03 mg/kg/day (max 7.5 mg/day). The annual cumulative steroid dose was calculated by dividing the total steroid intake by 365.25 times the number of follow-up years. Collected data included SLEDAI and SDI scores at initial and final visits, laboratory parameters, and flare characteristics.ResultsA total of 158 patients (86.7% female) from 17 centers were included. Median age at diagnosis was 13.8 years, with a median follow-up of 35 months. Organ damage was present in 14 patients at diagnosis and in 23 at final visit. Damage types included proteinuria, cognitive dysfunction (each 3.2%), and others such as cataracts, erosive arthritis, avascular necrosis, optic atrophy, and vertebral collapse. Patients with damage had significantly higher SLEDAI scores at both time points, delayed transition to low-dose steroids, and a lower rate of achieving Lupus Low Disease Activity State (LLDAS) (p = .006).ConclusionPersistent disease activity and delayed control are major contributors to organ damage in jSLE. Early and sustained disease suppression is critical to prevent long-term complications.

ObjectiveTo estimate the prevalence of Systemic Lupus Erythematosus (SLE) in Peru in 2017 and its association with altitude, environmental temperature, and physician density.MethodsThis ecological study was performed using population data from the 2017 Peruvian census. The number of SLE cases for each department was obtained from the National Health Registries using the ICD-10 code M32. Altitude, environmental temperature and physician density were obtained for each department from the National Institute of Statistics and Informatic (Instituto Nacional de Estadística e Informática) registries. The prevalence for each department was calculated adjusting for age and sex. Then a negative binomial regression was performed to estimate the prevalence ratio (PR) and evaluate factors associated with the prevalence of SLE.ResultsThe national prevalence of SLE was 40.2 per 100,000 people. Two age groups had the highest prevalence: 12-17 years and 30-59 years. Females exhibited a higher prevalence than males, particularly in the 30-59 age group (113.9 vs 16.1 per 100,000, respectively). An inverse relationship was observed between the age- and sex-adjusted prevalence in each department and altitude (PR 0.97; 95% CI: 0.94-0.99). On the other hand, there was a direct relationship with physician density (PR: 1.04; 95% CI: 1.01-1.07). No association was found between the adjusted prevalence and environmental temperature or latitude.ConclusionThe prevalence of SLE in Peru aligns with global estimates. The inverse relationship with altitude and the direct association with physician density suggest that environmental and healthcare access factors may influence disease distribution. Further research is needed to explore the underlying mechanisms driving these associations.

BackgroundLupus nephritis (LN) is a key manifestation of systemic lupus erythematosus (SLE).Aim of the workTo assess urinary transferrin level, renal iron accumulation and transferrin receptor (TfR) gene expression in SLE.Patients and methodsA case-control study was conducted on 80 SLE patients (40 with LN and 40 without LN), and 90 age and sex matched healthy control. Iron markers (Serum iron, ferritin, TfR gene, and urinary transferrin) were assessed in all participants. Iron accumulation and TfR gene expression were evaluated in renal biopsy for LN cases. Disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index-2K(SLEDAI2k).ResultsOf 80 patients, 85% were female. Mean SLEDAI was 15.0525 ± 1.1592, the disease duration was of mean 47.6 ± 26.56 months, and mean age was 31.32 ± 8.85. Serum and urinary iron biomarkers were significantly higher in SLE patients compared to controls except for iron which was lower in lupus patients with similar significant difference between patients subgroups. TfR gene expression in renal tissue didn't significantly differ across LN classes. Tubular iron deposition was observed histopathologicaly. Urinary transferrin showed significant correlation with activity score and proteinuria (r = 0.94, r = 0.43 and p < .0001, p = .03) while serum TfR significantly correlated with disease activity and ESR (r = 0.61, r = 0.4 and p < .0001, p = .03, respectively). TfR gene expression on renal tissue did not correlate with urinary transferrin, disease activity or other laboratory parameters.ConclusionsElevated urinary transferrin and serum TfR correlated with disease activity in lupus population and may serve as a potential non-invasive biomarker for lupus nephritis.

ObjectiveTo systematically compare the clinical effectiveness and safety of Belimumab, Rituximab and Voclosporin in the treatment of lupus nephritis based on network meta-analysis method.MethodsSystematic search of registered clinical trials in four major databases (Pubmed, Embase, Web of Science, The Cochrane Register of Clinical Trials) and ClinicalTrials.gov. According to the inclusion and exclusion criteria of the protocol, Screening of registered randomized controlled clinical trials of Belimumab, Rituximab and Voclosporin in the treatment of lupus nephritis.ResultsThis study included a total of five registered randomized controlled clinical trials involving 1212 subjects. In terms of complete renal remission, Voclosporin -1 year, High-Voclosporin-1 year, Voclosporin-2 years and Belimumab-2 years were all significantly better than placebo; At the same time, the effect of Voclosporin-1 year on complete renal remission rate was significantly better than that of Rituximab-1 year [OR = 3.2, 95% CI (1.41,7.24)]. In terms of safety, placebo was significantly better than High-Voclosporin-1 year [OR = 0.23, 95% CI (0.07,0.82)], and the difference was statistically significant; There was no significant difference in the incidence of serious adverse events.ConclusionVoclosporin and Belimumab showed significant clinical efficacy in the treatment of lupus nephritis, and the safety was not statistically different from placebo. Voclosporin had significantly better clinical efficacy than Rituximab during 1-year treatment period. Increasing the dose of Voclosporin did not significantly improve the efficacy, but it will increase the safety risk of adverse events.

ObjectiveAccurate diagnosis and continuous monitoring are crucial for effective management of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Conventional biomarkers exhibit limitations regarding their sensitivity and specificity. Recent research highlights the importance of DNA methylation, particularly in the PARP9 gene, in relation to these diseases. This study examines PARP9 promoter methylation in peripheral blood mononuclear cells (PBMCs) obtained from SLE and RA patients to evaluate its diagnostic potential.MethodsIn this study, we assessed the quantitative methylation levels of the PARP9 promoter in PBMCs from 75 SLE patients, 75 RA patients, and an equal number of healthy controls using methylation-quantification of endonuclease-resistant DNA (MethyQESD) method.ResultsThe study revealed significant hypomethylation of the PARP9 promoter in both SLE and RA patients compared to control group (p < .001). The optimal cutoff values identified were 24.31% for SLE, demonstrating a sensitivity of 81.33%, and a specificity of 77.33%, and 27.73% for RA patients with a sensitivity of 77.33%, and a specificity of 70.66%). ROC curve analysis showed an AUC of 0.758 for SLE and 0.717 for RA, reflecting a moderate diagnostic accuracy (p < .001). Additionally, hypomethylation of PARP9 was negatively correlated with anti-dsDNA levels in SLE patients and with ESR and CRP levels in RA patients, while showed a positive correlation with C3 and C4 levels in SLE group (p < .001).ConclusionPARP9 promoter hypomethylation shows potential as a diagnostic biomarker for SLE and RA. The significant association between hypomethylation of PAPR9 promoter and disease activity factors in SLE and RA patients, is suggesting that PARP9 hypomethylation could be used as an alternative biomarker for monitoring of disease activity.

ObjectiveTo detect the expression levels of TWEAK and CD163 in monocytes from the peripheral blood of patients with systemic lupus erythematosus (SLE) complicated with renal involvement (SLE+RI) and to explore the application value of TWEAK and CD163 in the diagnosis of SLE and SLE+RI.MethodsThe expression levels of TWEAK and CD163 in the monocytes of 70 SLE patients and the control group were determined by real-time fluorescence quantitative polymerase chain reaction (RT‒qPCR). To analyse the relationship between TWEAK/CD163 expression levels and laboratory examination and clinical manifestations in monocytes of SLE+RI patients. The sensitivity and specificity of TWEAK and CD163 for the diagnosis and differential diagnosis of SLE+RI were analysed by receiver operating characteristic (ROC) curves. Western blot experiments were used to evaluate the protein expression of TWEAK and CD163 in monocytes.ResultsThe expression levels of TWEAK and CD163 in monocytes were significantly greater in the SLE group than in the healthy control (HC) and rheumatoid arthritis (RA) groups. The expression levels of TWEAK and CD163 in monocytes from anti-double-stranded DNA antibody (anti-dsDNA)-positive patients and patients with proteinuria were respectively greater than those from anti-dsDNA-negative patients and patients without proteinuria. The expression levels of both genes were significantly lower after treatment than before treatment in the SLE+RI group (p < 0.05). The expression levels of TWEAK and CD163 in monocytes were positively correlated with the SLE activity score (SLEDAI) in the SLE+RI group. ROC curve analysis revealed that the area under the curve (AUC) of TWEAK expression was 0.869 in the SLE+RI group. The AUC of CD163 in the SLE+RI group was 0.792, the combined expression of TWEAK and CD163 was 0.842 in the SLE+RI group. TWEAK and CD163 protein expression in monocytes from patients with SLE+RI was significantly increased compared with that in controls.ConclusionThe expression levels of TWEAK and CD163 are increased in SLE patients, and the expression levels in SLE+RI patients are greater than those in SLE-RI patients. These findings are closely related to disease activity, autoantibody production and clinical symptoms and can be used as biomarkers for the diagnosis and activity of SLE+RI.

PurposeSystemic lupus erythematosus (SLE) is a chronic autoimmune disease that associated with great mortality. However, studies on survival & predictors mortality in SLE are lacking in developing countries in Asia region. To calculate survival rates and to determine the cause and suggestive risk factors of mortality in SLE patients.Patients and methodsThis study included all SLE patients in Hasan Sadikin Lupus Registry (HSLR) cohort in Hasan Sadikin Hospital Bandung between September 2001 to December 2020. Cox-regression model was used to determine the risk factors of mortality, whereas Kaplan-Meier method used to estimate survival probabilities since diagnosis.ResultsThere were 1263 patients included in this study and 125 of them were deceased. Infection (40.8%) was the most common cause of death. The 1, 5 and 10-year survival rate among our patients were 95.6%, 89.7% and 82.1%, respectively. Male sex (HR 1.89), active SLE (HR 6.06), hemolytic anemia (HR 1.62) and serositis (HR 1.74) involvement throughout the disease, and use of methylprednisolone pulse (HR 1.75) due to high disease activity significantly affect mortality. On the other hand, the use of azathioprine (HR 0.61), mycophenolic mofetil/ mycophenolic acid (MMF/MPA, HR 0.43), and anti-malaria (chloroquine/hydroxychloroquine (CQ/HCQ)) (HR 0.5) had protective effect towards mortality.ConclusionSurvival rates of SLE patients was still low in Indonesia. Hemolytic anemia and serositis involvement throughout the disease, male sex, and active SLE, along with the use of methylprednisolone pulse were significantly affect mortality of SLE in this study. Meanwhile the use of azathioprine, MMF/MPA, and anti-malaria therapy had protective effect on SLE mortality.

Case details: A 16-year boy had a history of rash, oral ulcers, alopecia, photosensitivity, cheilitis, and weight loss, for which he was started on steroids, methotrexate, and hydroxychloroquine from outside. Three years later, he developed pericardial effusion and peripheral neuropathy, that were managed at an outside hospital. Later, he presented to us with weight loss, diffuse rash, left facial palsy, and left lateral rectus palsy. CT aortogram revealed a string-of-pearls appearance involving the head, neck, thoracic, and visceral arteries. The child was diagnosed with severe lupus vasculitis with minimal systemic symptoms. This child responded well to the methylprednisolone and cyclophosphamide.Conclusions: This is a unique example of the classical multisystemic presentation of lupus and its rare manifestation of extensive systemic vasculitis.

ObjectiveLupus nephritis (LN) is a common complication in a significant proportion of systemic lupus erythematosus (SLE) patients. As a chronic autoimmune disease, LN leads to renal failure, substantially impacting patient quality of life and mortality rates. Current LN treatments primarily involve traditional immunosuppressants, such as azathioprine and mycophenolate mofetil (MMF). However, a subset of patients exhibits poor responsiveness to these therapies.MethodsTo identify genes specifically upregulated in this non-responder group, we analyzed RNA-sequencing data from the tubulointerstitial regions of LN patients and single-cell RNA-sequencing data from non-response LN patients, using datasets obtained from public databases. ResultsThis analysis revealed an increased epithelial-to-mesenchymal transition (EMT) signature in the LN patients, and identified COL3A1, TNC, and PDGFRA as commonly upregulated genes in both general LN patients and non-responder LN patients. Further validation using single-cell RNA-sequencing confirmed that these genes are predominantly expressed in renal tubular epithelial cells. Furthermore, analysis of three additional independent LN datasets confirmed that COL3A1, TNC, and PDGFRA were significantly upregulated in the tubulointerstitial regions of other LN patient cohorts. ConclusionThis study suggests that the non-responder group may exhibit enhanced EMT features, particularly involving the upregulation of COL3A1, TNC, and PDGFRA in the tubulointerstitial region. Therefore, these findings may aid in identifying potential biomarkers for difficult-to-treat patients and offer valuable insights into possible therapeutic targets for LN management.

Pregnancy is an altered immunologic state in which hormonal changes affect the immune system to enable maternal tolerance of the fetus. These hormonal and immunologic changes may influence systemic lupus erythematosus disease activity. Managing lupus nephritis in pregnancy presents diagnostic and therapeutic challenges for healthcare providers. Pregnancy induces a series of physiological changes in the immune system and kidneys, increasing the risk of disease flare and adverse maternal and fetal outcomes, such as preeclampsia, fetal loss, and preterm delivery. Kidney biopsy can be risky due to the high risk of complications and should be considered if its results would influence management. The risks associated with kidney biopsy are relatively low in early pregnancy. Pregnancy should be planned during periods of well-controlled lupus nephritis. The antimalarial drug hydroxychloroquine should be continued, and the only permitted immunosuppressive drugs are azathioprine and tacrolimus. Preconception preparation could prevent maternal-fetal complications.