Lupus最新文献

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.

IntroductionSystemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that often manifests during productive years and frequently involves the central nervous system (CNS), including cognitive dysfunction, which occurs at twice the prevalence of the general population. While the Montreal Cognitive Assessment (MoCA) is effective for detecting mild cognitive impairment, no reliable biomarkers that indicate SLE patients at risk of cognitive dysfunction exist. Neuron-specific enolase (NSE), a specific marker of neuronal cell damage, has been shown in several studies to be highly expressed in cognitive dysfunction. This study serves as a preliminary investigation to examine the relationship between serum NSE levels and cognitive function in SLE patients.MethodsA cross-sectional study was conducted from January to August 2024 at Hasan Sadikin General Hospital, including SLE patients aged 18-55 years meeting the EULAR/ACR 2019 criteria. Exclusion criteria included pregnancy, neurological disorders (e.g., CNS infections, neurodegenerative diseases, stroke, epilepsy, head trauma), psychiatric conditions, substance abuse, systemic metabolic disorders, malignancy, other autoimmune diseases, or HIV. Cognitive function was assessed using MoCA-Indonesian version (MoCA-Ina) and serum NSE levels were measured. Associations between serum NSE and MoCA-Ina scores were analyzed using Spearman's correlation (p < .05).ResultsEighty-one participants (median age 32 years; 93.8% female) were included. Cognitive dysfunction (MoCA-Ina <26) was identified in 38.3%. Median serum NSE levels were higher in participants with cognitive dysfunction compared to those with normal cognition (14.0 ng/mL vs 12.7 ng/mL). Serum NSE levels showed a negative correlation with MoCA-Ina total scores (r = -0.225, p = .022) and executive function (r = -0.204, p = .034). Cognitive dysfunction was also associated with longer disease duration and a history of seizures.ConclusionThis study demonstrates a significant association between neuronal injury, as indicated by elevated serum neuron-specific enolase (NSE) levels, and cognitive impairment in SLE patients, with a particular impact on executive function. Longitudinal studies incorporating neuronal biomarkers are essential to provide deeper insights into the progression of cognitive dysfunction in SLE patients.

BackgroundSystemic Lupus Erythematosus (SLE) is a heterogeneous multisystem autoimmune disease, with variable severity, autoantibody profile, response to treatment, relapsing course and damage accrual. The age at disease onset may influence disease trajectory and prognosis, with remarkable differences of major organ involvement, disease activity, and prognosis. SLE clinical profile, activity indices, remission, and damage comparison were carried out in childhood-onset (cSLE), adult-onset (aSLE) and late-onset (lSLE) patients from a single-centre series.MethodsA cross-sectional analysis reviewing the clinical profile of SLE cases seen between 2012 and 2022 and classified in 3 age-groups according to disease onset: cSLE (<18 years), aSLE (18 to 49 years) and lSLE (>=50 years), was performed. Disease activity status was assessed by PGA (0-3), SLEDAI-2K, SLE-DAS, LLDAS and DORIS criteria, and damage using SDI at the same visit were compared in those 3 age-groups.ResultsFour hundred and fifteen patients were included in the analysis: 289 (68%) aSLE, 79 (19%) cSLE, and 47 (11.3%) lSLE. Most common clinical manifestations were articular (75.2%), hematological (70.1%), cutaneous (67.9%), photosensitivity (59.3%), and renal (41.7%). The clinical profile was similar among the subgroups of SLE patients, except for lSLE with lower frequency of nephritis and serositis, lower frequency of autoantibodies and hypocomplementenemia, lower SLEDAI-2K and SLE-DAS scores, and a higher frequency of LLDAS and DORIS remission; and a higher damage scores (SDI). Patients with cSLE had a significantly higher frequency of renal and neurological involvement, and a longer disease duration, but the disease activity, damage scores and remission rates were comparable to adult-onset group.ConclusionThe remarkable differences among the 3-age-groups were higher frequency of renal and neuropsychiatric domains in youngsters and disease activity scores compared to other age-groups. The lSLE group had less nephritis and serositis, lower disease activity and higher damage scores.

ObjectivesAvascular necrosis (AVN) is a common complication of Systemic Lupus Erythematosus (SLE) that causes significant morbidity for patients. This study aimed to determine the prevalence of symptomatic AVN in a large SLE cohort and to determine clinical and serological risk factors for symptomatic AVN overall and in early-onset and later-onset AVN subgroups.MethodsPatients with symptomatic AVN (n = 106) and those without AVN (n = 197) were identified in a cohort of 912 patients with SLE and followed up by a standard protocol in this retrospective case control study. Osteonecrosis was recorded when there was radiological evidence. Patients who developed AVN within the first year of SLE diagnosis were compared to those at a later stage as well as all AVN patients to 197 patients without AVN matched for disease duration. SLICC SLE damage index (SDI), and the disease activity (SLEDAI-2K) were determined at AVN diagnosis.ResultsThe prevalence of symptomatic AVN in our SLE cohort (n = 912) was 11.6% (n = 106). The mean age at SLE diagnosis of AVN patients were significantly lower than non-AVN patients (27.6 ± 10.6 vs 32.5 ± 12.6; p = .003). SLE-AVN patients had significantly higher alopecia, photosensitivity, oral ulcers, vasculitic skin rash, artritis, serositis, nephritis, pulmonary hypertension and neurologic involvement than non-AVN SLE patients (p < .05). Compared with the control group, SLE patients with AVN had significantly higher anti-cardiolipin IgG, lupus anticoagulant and anti-phospholipid antibody positivity of any kind (p = .020; 0.020; 0.018, respectively). In 106 patients, AVN was found in a total of 214 joints. Of the patients, 64.2 % (n = 68) had AVN in more than 1 joint. Patients who had AVN ≤1 year after SLE diagnosis had significantly higher mean SLEDAI-2K, higher mean daily steroid dose until diagnosis, and lower age (p = .041; 0.000 and 0.001, respectively). These patients also developed AVN at multiple joints significantly more than other patients (p = .047).ConclusionWe believe that controlling disease activity in the first year of SLE diagnosis and keeping daily steroid dose at minimum levels could be important in preventing early development of debilitating AVN in multiple joints, especially in younger SLE patients.