Lupus最新文献

Background: Laboratory-based biomarkers accurately presenting systemic lupus erythematosus (SLE) disease activity may have a practical value in clinical routine. As shown in many other conditions, complete blood count (CBC)-derived biomarkers may also play a role in SLE.

Objectives: We aimed to study for the first time the pan-immune-inflammation value (PIV, monocytes x platelets x neutrophils/lymphocytes) and the more established systemic immune-inflammation index (SII, neutrophils x platelets /lymphocytes) in SLE patients and correlate it with serological and clinical findings including disease outcomes.

Methods: In this retrospective multicentric investigation, we reviewed the clinical records of 148 SLE who had an available CBC at baseline. The latter served for the determination of the neutrophil-to-lymphocyte ratio (NLR), SII, and the PIV. Control groups were studied as well. Univariable as well as multivariable statistics were employed.

Results: The values for baseline systemic immune-inflammation biomarkers (SIIB) studied were significantly (p < 0.0001) higher than those observed in healthy controls but comparable to those obtained from patients with other inflammatory conditions. Multivariable analysis revealed that ANA titer > 1:640 remained the only significant (p < 0.0001) baseline predictor of SLE flare (odds ratio: 7.6, 95% CI 3.1 to 18.8). Improvement of SLE following treatment was associated with the absence of lymphopenia as well as ANA > 1:640 (p = 0.041). The SLEDAI-2K significantly correlated with NLR, SII, CRP, lymphocytes, and monocytes only on univariable testing.

Conclusions: Compared to healthy controls the CBC-based SIIB investigated are significantly increased in SLE patients. However, SIIB do not appear to be useful in managing SLE clinically. Nevertheless, we confirm that higher ANA titers can predict flares of SLE.

Introduction: Heterogeneity of the clinical manifestations of systemic lupus erythematosus (SLE) may lead to diagnostic delays. This study is aimed at determining the health-seeking behaviour patterns and factors associated with diagnostic delays in a multi-ethnic SLE cohort in Malaysia.

Methodology: This was a cross-sectional study involving SLE patients who visited our institute between January 2020 and June 2021. A review of the medical records and face-to-face interviews were conducted to obtain sociodemographics, SLE disease characteristics and the intervals from the first symptoms to the diagnosis. Health-seeking behaviours were assessed by asking about the patients' first action during the initial symptoms and were divided into: (i) seeking professional health personnel; (ii) self-treatment; and (iii) the use of the internet as a primary source of information. Diagnostic delays were defined as the interval between initial symptoms and SLE diagnosis of more than 6 months. Low-level disease activity state (LLDAS) at 12 months was assessed from the medical records. Univariate and multivariate logistic regression analysis was subsequently conducted to determine factors associated with diagnostic delays.

Results: Among the 154 patients included in the study, 24% (n = 37) had delayed diagnosis. The delay was significantly higher among the Indian versus Malay versus Chinese (42.9% vs 28% vs 10.8%, p = 0.037). Patients with rash tend to have delayed diagnosis (37.8% vs 22.2%, p = 0.08) while fewer patients with frothy urine had delayed diagnosis (8.1% vs 21.4%, p = 0.09). No significant association was found between health-seeking behaviours and diagnostic delays. The rate of LLDAS at 12 months was significantly lower among patients with delayed diagnosis (43.2% vs 70.0%, p = 0.006). Chinese ethnicity remained the only significant factor associated with lesser diagnostic delays in the multivariate analysis, with OR 0.30 (CI 0.09-0.93), p = 0.037.

Conclusion: There were ethnic disparities in the early diagnosis of SLE in Malaysia, with Indian patients having a longer interval between the first symptom and diagnosis while the Chinese were associated with lower diagnostic delays. Early diagnosis predicted early attainment of LLDAS, suggesting that prompt recognition of the initial SLE symptoms is important.

Background: Lupus anticoagulant hypoprothrombinemia syndrome (LAHPS) is a rare autoimmune condition characterized by acquired prothrombin (FII) deficiency associated with antiphospholipid syndrome (APS) and life-threatening bleeding. We present the case of a 34-year-old woman with heavy menstrual bleeding (HMB), positive Lupus anticoagulant (LA) test, and high titer anticardiolipin antibodies Immunoglobulin G (ACA IgG) and anti-β2 glycoprotein I antibodies IgG (antiB2GPI IgG). Severe iron deficiency anemia necessitated recurrent blood transfusions and intravenous iron infusions from 2018 to 2021.

Results: In January 2022, she was admitted to our clinic. Von Willebrand disease screening and platelet function analysis (PFA100) were normal. FII and FIX deficiencies were detected, without factor IX inhibitors. Anti-phosphatidylserine/prothrombin antibodies were confirmed by Padua University lab. To reduce antibody titers and menstrual bleeding, immunosuppressive therapy (Rituximab 375 mg/m2 weekly ×4 weeks) and hormonal therapy (desogestrel 75 mcg/day) were initiated.

Conclusion: After 1-year, complete remission of clinical symptoms was achieved, with normalization of FII and FIX values and moderate reduction of aPS/PT titers, especially IgM isotype.

Background: Systemic lupus erythematosus (SLE) is a complex autoimmune disorder characterized by a malfunction of the body's immune defense system.

Objective: The objective of the present investigation was to examine the expression and diagnostic significance of NRIR in SLE and to prove whether it is involved in the progression of SLE.

Methods: The study involved 110 participants, including 55 healthy individuals and 55 SLE patients. The expression levels of NRIR, miR-31-5p, and ICAM-1 were measured using qRT-PCR. The ROC curve was performed to assess the diagnostic significance of NRIR in SLE patients. Pearson correlation analysis was utilized to explore the relationship between NRIR and other indicators. Cytokines including IL-4, IL-6, and IL-21, along with IgG levels, were assessed using ELISA. The interaction between NRIR and miR-31-5p was validated using a dual-luciferase reporter assay.

Result: Upregulated expression of NRIR was observed in individuals with SLE, serving a diagnostic function for SLE. Additionally, abnormal expression of NRIR impacted the viability of CD4⁺ T cells within SLE patients. NRIR could negatively modulate the expression of miR-31-5p.

Conclusion: LncRNA NRIR may be a potential biomarker for SLE and is likely involved in the progression of SLE.

Objective: As suggested by the EULAR recommendations, a comprehensive management of Systemic Lupus Erythematosus (SLE) should include the evaluation of disease activity, chronic damage, and quality of life (QoL). QoL is significantly impaired in SLE patients, even in those achieving a state of remission, suggesting the possible contribution of other factors. Thus, in the present study we aimed at analyzing QoL in a large SLE cohort by using LupusQoL, and at identifying the main determinant of poorer QoL.

Methods: We conducted a cross-sectional study by including consecutive SLE patients diagnosed according to the 2019 ACR/EULAR criteria. Clinical, laboratory and therapeutical data were collected. Disease activity was assessed by SLEDAI-2k, while chronic damage by the SLICC Damage Index (SDI). The diagnosis of fibromyalgia was made in accordance with the ACR criteria (2016). At the time of the enrollment, all patients completed the following questionnaires: LupusQoL to assess quality of life and hospital anxiety and depression scale (HADS) for anxiety and depression.

Results: Our analysis included 237 SLE patients [92.4% female, median age 46 years (IQR 19.5), median disease duration 156.8 months (IQR 180.6)]. At the time of enrollment, we found a mean SLEDAI-2k of 1.7 (DS 2.4); 104 patients (43.9%) had chronic damage, with a mean SDI value of 0.8 (DS 1.3). Patients diagnosed with fibromyalgia were 69 (29.1%); moreover, HADS questionnaire identified a condition of anxiety and depression in 112 (47.3%) and 94 (39.7%) patients, respectively. The most compromised domain in the LupusQoL resulted "fatigue", followed by "burden to others". Patients with SDI ≥ 1 showed lower quality of life than patients without chronic damage, as demonstrated by significantly lower values in all items of the LupusQoL (p < .01). Furthermore, significantly lower values in all the LupusQoL domains were observed in patients with fibromyalgia, anxiety and depression, in comparison to those patients without these manifestations (p < .0001). No association was demonstrated between QoL and disease activity. Finally, the linear regression analysis confirmed mood disorders, in particular depression, and fibromyalgia as the main determinants of worse quality of life in our cohort.

Conclusions: The present study demonstrated the influence of different factors in the quality of life of SLE patients. In particular, the presence of mood disorders, fibromyalgia and chronic damage resulted the main determinants of poorer QoL. This evidence reinforces the need for a comprehensive patient care.

Background: Systemic lupus erythematosus (SLE) increases the risk of interstitial lung disease (ILD). SLE is also linked to an elevated risk of type 2 diabetes mellitus (T2DM). However, the impact of T2DM on ILD risk in patients with SLE is still unclear. This study aimed to compare the prevalence of ILD in patients with SLE based on the presence of T2DM (SLE + T2DM+) or its absence (SLE + T2DM-).

Methods: This was a retrospective cohort study using the 2019-2020 National Inpatient Sample database. Adult SLE patients were identified and stratified by T2DM status. Comparable cohorts were created using propensity score matching, resulting in 10,532 patients in each cohort. Multivariate logistic regression assessed the association between T2DM and ILD.

Results: T2DM was associated with a lower prevalence of ILD in patients with SLE (OR 0.798, 95% CI: 0.695-0.918, p = .002), occurring in 371 (3.5%) patients with T2DM compared to 463 (4.4%) patients without T2DM. Specifically, this difference was mainly driven by pulmonary fibrosis, which was significantly less frequent in the T2DM group (1.3% vs 1.8%, OR 0.7, 95% CI: 0.560-0.875, p = .002). No differences were found in secondary outcomes, including death rates, length of hospital stay, ARDS, pneumothorax, pleural effusion, or pulmonary arterial hypertension.

Conclusion: Our study suggests that T2DM significantly reduced ILD risk in patients with SLE, specifically diminishing pulmonary fibrosis prevalence. Further research should explore mechanisms for this protective association between T2DM and ILD development in SLE. These findings may guide management strategies for this vulnerable population.

Objective: to investigate the trend of autoantibody titers during a 2-year follow-up in pediatric systemic lupus erythematosus (pSLE) and pediatric Sjögren's syndrome (pSS).

Methods: Autoantibodies testing was performed every 3-4 months during 2 years from disease onset in a cohort of children with pSLE and pSS.

Results: We enrolled 21 children with pSLE and 22 children with pSS. All pSLE patients at 2 years showed ANA titers significantly lower compared to disease onset. Eleven patients (73%) were still ANA positive at 2 years, while 4 (26%) became ANA negative. At diagnosis, 12 (80%) patients showed a homogeneous pattern, while 3 (20%) patients showed a speckled pattern. The latter remained ANA positive with the same pattern; only 2 patients with a homogenous pattern converted to speckled, 4 patients with a homogeneous pattern became ANA negative. ANA negative pSLE patients showed lower levels of interferon score compared to ANA positive patients. Anti-dsDNA titers declined equally in the two groups. All patients with pSS, at disease onset, were ANA and anti-Ro positive and 14 (66%) were anti-La positive. After 2 years of follow-up, 100% remained ANA positive but showed significant lower titers. During follow-up anti-Ro and anti-La titers remained stable.

Conclusion: different patterns in changes of ANA and ENA titers in pSLE and pSS were shown. At 2 years of follow-up, all pSLE patients had a lower ANA titer and 26% became negative; however, all pSS patients remained both ANA and ENA positive. This evidence may be due to different pathogenetic pathways in SLE and pSS.

Objective: Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice.

Methods: This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24 weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit.

Results: Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI.

Conclusion: Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24 weeks will extend this current body of evidence.

Objective: The aim of our study was to evaluate the renal response (RR) of three immunosuppressive protocols in the induction treatment of proliferative lupus nephritis (PLN) in a Tunisian population.

Methods: We performed a retrospective prognostic cohort study in the Internal Medicine Department of the Habib Thameur University Hospital in Tunis from January 2000 to December 2023, and included kidney biopsy proven proliferative lupus nephritis patients. Three induction treatments were compared: High CYP regimen: glucocorticoids (GC) + IV cyclophosphamide (CYP) in monthly pulses of 0.7 g/m2 for 6 months; Low CYP regimen: GC + IV CYP in biweekly pulses of 500 mg for 3 months; and MMF regimen: GC + oral MMF 1.5 g twice daily for 6 months. The primary endpoint was the incidence of RR (complete and partial remission) at one year post-diagnosis. The additional outcomes were end-stage kidney disease (ESKD), severe adverse events (AEs) and death.

Results: Our study included 78 PLN patients (High CYP: 17, Low CYP: 40, MMF: 21). The study found that 94.1% of patients receiving High CYP achieved the primary endpoint, RR, compared to 67.5% of those receiving Low CYP and 61.9% in the MMF group. For the additional outcomes, there were 3 cases of ESKD, all in the Low CYP group, 5 cases of death (4 in the Low CYP group and 1 in the MMF group), and 20 cases of severe AEs, all of which were severe infections (5 in the High CYP group, 12 in the Low CYP group, and 3 in the MMF group). Multivariate analysis showed that the High CYP regimen was more associated with RR than the MMF regimen, with an adjusted OR of 9.846 (95% CI: 1.087-98.210); p = 0.042. Multivariate analysis did not show statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR.

Conclusion: As an induction treatment for PLN, the High CYP regimen was strongly associated with a higher rate of RR than the MMF regimen. There were no statistically significant differences between the High CYP regimen and the Low CYP regimen in terms of RR.

Background: Lupus nephritis (LN) is the most serious complication of systemic lupus erythematosus (SLE), and plasma exosomes may serve as a bridge. MicroRNAs (miRNAs) are abundant in exosomes, so this study aimed to explore the role of exosome-derived miRNA in the development of LN.

Methods: The publicly available data containing plasma exosomal miRNAs in SLE patients and healthy controls were researched, and differential expression and functional enrichment analysis of exosomal miRNA was conducted. Then, plasma exosomes from SLE patients were extracted, and the accuracy of differential expression and functional enrichment analysis was preliminarily verified. PKH26 dye was used to label exosomes to detect whether exosomes can enter HK2 cells. Evaluation of plasma exosomes impact on cell viability was done by utilizing CCK-8 assay. Flow cytometry was used to measure cell apoptosis.

Results: Plasma exosomes were successfully extracted and identified. Through differential expression analysis of the pulbilic data and subsequent qPCR validation, we observed that miR-20b-5p is overexpressed in plasma exosomes of SLE patients, whereas miR-181a-2-3p is downregulated. Then functional enrichment analysis revealed that these differential miRNAs primarily regulate processes such as apoptosis, autophagy, and inflammation. Then, flow cytometry analysis conducted after co-incubation of plasma exosomes and peripheral blood mononuclear cells confirmed that exosomes can indeed regulate apoptosis. And plasma exosomes can successfully enter HK2 cells without affecting cell activity. In addition, plasma exosomes promote HK2 cell apoptosis and autophagy. Overexpression of miR-181a-2-3p could inhibit HK2 cells apoptosis and upregulate the expression of bcl2, and beclin1. At the same time, a trend towards increased apoptosis rates was observed in HK2 overexpressed miR-20b-5p, although the difference did not reach statistical significance. And miR-20b-5p can enhance the expression of caspase3 and becin1 while suppressing the expression of bcl2 and LC3β.

Conclusion: Our research indicates that the abundant presence of miR-20b-5p and the depletion of miR-181a-2-3p in plasma exosomes of SLE patients may mediate the promotion of apoptosis and autophagy in HK2 cells, thereby causing kidney damage and the development of LN.