Lupus最新文献

Background: Infections are a major cause of morbidity and mortality in juvenile systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in juvenile SLE.

Methods: A retrospective review of 225 patients of juvenile SLE (ACR 1997 criteria) with age <18 years visiting the rheumatology clinic at a single centre between 2000 to 2020 was done from case records and the hospital electronic health records. Serious infection was defined as the need for hospitalization, or infection resulting in disability or death. Cox regression was used to determine factors associated with a serious infection and the effect of serious infection on overall survival.

Results: We reviewed 225 children (197 girls, mean age 13.89 ± 3.42 years) with a cumulative follow up of 1153.45 person-years. Eighty serious infections occurred in 63 (28% of the cohort) children at a rate of 69.35 serious infections per 1000 person-years. A second serious infection occurred in 12 children and 5 of them developed three infections.Among the cases with known etiology (78.75% of cases), bacterial infections were most common (N = 33) including S. Aureus (11), E. Coli (7), K. Pneumoniae (3), E. Fecalis (3), S. Pneumoniae (2), Acinetobacter spp. (2), Citrobacter (2), Salmonella (2) and P. Aeruginosa (1). Twenty six (32.5%) opportunistic infections occurred: Mycobacterium tuberculosis (18), Cytomegalovirus (3), disseminated Herpes zoster (4) and invasive candidiasis (1) with 15 (83.3%) of the tuberculosis cases being extrapulmonary. On multivariate analysis, fever (HR 8.51, 1.17-61.44), gastrointestinal involvement (HR 4.73, 1.13-19.94), current steroid dose (HR 1.36,1.14-1.62), average cumulative steroid dose per year (HR 1.004, 1.002-1.005) and cyclophosphamide (HR 2.22, 1.11-4.46) were associated with serious infection.Hospitalization rates were significantly higher in those with any serious infection (Rate-ratio 2.79, 1.81-3.77) as was damage accrual (SLICC damage index 1.04 vs 0.22). Serious infection-free survival at 1 year and 5 years was 84% (79.1-89.2) and 72% (65.4-79.2). There were 19 deaths with infection attributable mortality in 10 (52.6%). Serious infection predisposed to higher overall mortality with recurrent infections conferring a hazard ratio of 36.02 (8.07-160.62).

Conclusion: Serious infections are a major cause of mortality and damage in SLE. Constitutional symptoms, gastrointestinal involvement, current and cumulative steroid dose and cyclophosphamide predict serious infections. TB prophylaxis in patients with SLE should be considered in endemic areas, especially when using high-dose steroid therapy.

Objective: Cognitive impairment (CI) in systemic lupus erythematosus (SLE) is quite common and is an important prognostic factor due to its severity. The aim of our study was to determine the proportion and type of CI in SLE and to identify associated risk factors.

Methods: We performed a cross-sectional study (January - March 2022). Participants included SLE patients and controls (No-SLE). SLE patients were subdivided into those with and those without CI to identify associated risk factors. CI was defined based on the results of eight specific tests assessing various cognitive functions, with MMSE used for overall cognitive assessment. Impairment was indicated by abnormalities in at least five of these eight functions.

Results: Our study included 60 lupus and 40 non-lupus participants. The median disease duration of patients in the SLE group was 72 months (interquartile range: 24 - 150 months). The proportion of cognitive impairment in SLE was 31.7%. The comparative study of cognitive functions between the two groups of participants with and without SLE concluded that executive functions and verbal fluency were more impaired in the lupus group compared to the non-lupus group. It also concluded that there were no statistically significant differences in attention and concentration, episodic memory, working memory, calculation, visuospatial and visuoconstructive activity, or judgement. In the multivariate analysis, patients with SLE have a significantly higher risk of CI (Adjusted OR 3.76, 95% CI: 1.217 - 11.621) compared to non-SLE individuals. Each additional year of age increases the risk by 4.4% (Adjusted OR 1.044, 95% CI: 1.008 - 1.082). For factors associated with CI in SLE, the multivariate analysis concluded that the duration of corticosteroid therapy, by months, had an adjusted OR equal to 1.009 (CI (95%): 1.000-1.018), and the duration of education, by years, had an adjusted OR equal to 0.857 (CI (95%): 0.736-0.999).

Conclusion: Screening for CI in lupus patients is important, especially for those with factors associated with these disorders such as prolonged duration of corticosteroid therapy and shortened schooling.

Background: Lupus cystitis, a severe complication of systemic lupus erythematosus (SLE), presents considerable treatment challenges.

Purpose: This case report describes the use of telitacicept in treating severe SLE with lupus cystitis.

Research design: A single patient with lupus cystitis.

Study sample: A patient with symptoms including frequent urination, urgency, and acute urinary retention.

Data collection and analysis: Initial treatments included corticosteroid pulse therapy, immunoglobulin, and cyclophosphamide, which improved laboratory indicators but failed to alleviate symptoms of urinary retention. The patient was then treated with telitacicept.

Results: Significant alleviation of urinary retention was observed shortly after incorporating telitacicept into the treatment regimen. The patient's condition remained stable with no relapse during the subsequent 10 months of follow-up.

Conclusions: This case highlights the therapeutic potential of telitacicept for SLE patients who are unresponsive to conventional therapies, particularly those with severe manifestations such as lupus cystitis.

Introduction: Systemic lupus erythematosus (SLE) causes widespread inflammation and damage in affected organs. Severity is determined by the type of organ systems affected and the extent of involvement. SLE occurs in childhood or adulthood and disease severity varies according to age of onset. We compared disease features and changes in disease severity over time between childhood-onset (cSLE) and adult-onset SLE (aSLE).

Methods: Patients 0-64 years old, newly diagnosed with SLE during 2014-2020 were identified using the MarketScan® database. A validated algorithm was used to assess disease severity. Improving severity versus baseline was defined as a transition from a higher (severe) to a lower (mild/moderate) disease state during each evaluation period. Group comparisons were made using the Pearson chi-square test for categorical and t test for continuous measures.

Results: A total of 10,912 patients were included. Most (89.9%) were female with a mean age of 14.2 versus 44.6 years for cSLE and aSLE groups, respectively. Patients with cSLE were more likely to have severe disease at diagnosis (38.3% vs 10.7%; p < .0001) versus aSLE. The largest reduction in SLE severity occurred during 6 to <12 months post-index with cSLE experiencing the greatest improvement (36.7% vs 19.9%; p < .0001) compared with aSLE. However, despite improvements observed over time in cSLE, this group was still more likely to have severe disease at 0 to <6 months (26.4% vs 10.5%) and 6 to <12 months (14.4% vs 8.6%) post-index compared with aSLE patients (p < .01, all). For aSLE, the proportions of patients experiencing either an improvement or deterioration in symptoms was similar during 0 to <6 months and 6 to <12 months. However, during 12 to <24 months, nearly twice as many patients in this group experienced a deterioration in symptoms (30.1%) compared to improvement (15.6%).

Conclusions: Children with SLE present with greater symptom severity compared with adults. Although children were more likely to experience improvements following treatment, they had more active disease over time than aSLE patients. Disease severity remained stable for aSLE patients until the second year of follow-up, when more patients experienced a deterioration rather than improvement in symptoms.

Objective: Despite some study demonstrated the effectiveness of telitacicept in patients with systemic lupus erythematosus (SLE), a noticeable gap exists in real-world data. This study aimed to examine the effectiveness and safety of telitacicept in patients with SLE in the real-world.

Method: This retrospective study enrolled patients with SLE at the Tangdu Hospital from January 2022 to January 2023. These patients were administered telitacicept at 80 mg or 160 mg dosage. The observed outcomes were changes in the SLE Responder Index 4 (SRI-4), disease activity, renal function, and immunological indicators.

Result: Sixty-one patients were enrolled, with 60 patients completed the 24-week follow-up, and 30 completed the 52-week. The SRI-4 response rates at 4, 12, 24, and 52 weeks were 52.5%, 67.2%, 75.4%, and 80.0%, respectively. No statistically differences were observed in the SRI-4 response rates between the 80 mg and 160 mg doses at any of the time points (all p > 0.05). By 52 weeks, the Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index scores were significant decreased from baseline (p < 0.001), and complement 3 and 4 levels (p = 0.001), albumin levels (p = 0.004), and the overall change in glucocorticoid dosage (p < 0.001) were all significantly increased, with all showing significant changes over time (p < 0.001). During the study, 3 (4.9%) patients experienced infection, and 1 (1.6%) developed an allergy at the injection site.

Conclusion: Telitacicept exhibited a highly effective and favorable safety in patients with SLE, with improved renal and hematological manifestations and facilitated a reduction in glucocorticoid medication usage.

Background: Endoplasmic reticulum stress with protein misfolding has been introduced as a key pathogenetic mechanism in lupus nephritis (LN). Pregnancy is thought to exaggerate proteostasis, which leads to the accumulation of potentially pathogenic misfolded proteins in the urine, serum, and placenta particularly in women with preeclampsia. The detection of misfolded proteins is made using Congo red stain, which is referred to as congophilia. This study aimed to assess the predictive value of urinary congophilia as a marker of LN activity in pregnant and non-pregnant LN women.

Methods: Urine samples from non-pregnant LN women (n = 45), pregnant LN women (n = 12), as well as pregnant healthy controls (n = 38) were collected. Urinary congophilia was assessed by Congo Red Dot Blot assay. The disease activity was defined according to SLE Disease Activity Index (SLEDAI) score, and SLE Disease Activity Index-Renal Domain (SLEDAI-R) score. Renal biopsy was done for 33 non-pregnant LN women as it was clinically indicated, and modified NIH activity index (AI) was assessed according to the classification of LN by the International Society of Nephrology/Renal Pathology Society (ISN/RPS).

Results: Congo red retention (CRR) values were significantly higher for pregnant active LN patients, in comparison with pregnant inactive LN patients (p = .014), as well as pregnant healthy controls (p = .009). Additionally, CRR values were significantly higher for non-pregnant active LN patients, in comparison with non-pregnant inactive LN patients (p = .016), as well as pregnant healthy controls (p ≤ .001). There were significant positive correlations between CRR on one hand, and anti-ds-DNA (r = 0.791, p ≤ .001), serum creatinine (r = 0.620, p ≤ .001), SLEDAI score (r = 0.623, p ≤ .001), as well as SLEDAI-R score (r = 0.473, p = .005) on the other hand. A highly significant negative correlation was detected between CRR, and serum albumin (r = -0.454, p = .001). CRR at a cut point ≥21.85 had 83% sensitivity, and 58% specificity to capture high LN activity status (NIH-AI >10) versus lower LN activity status.

Conclusion: Urinary congophilia may add a diagnostic value in patients with LN and can be a reliable marker of disease activity. CRR is related to disease activity rather than pregnancy.

Background: Systemic lupus erythematosus is a common autoimmune disease. Studies have suggested that defective stem cells could be involved in the pathogenesis of systemic lupus erythematosus, which leads to changes in the function of immune cells. By observing the cell morphology, autophagy, and senescence of bone marrow mesenchymal stem cells (BMSCs) from lupus mice and normal controls, this study investigated the role of IL-6 in autophagy and senescence of BMSCs and explored relevant mechanisms.

Method: Female MRL/lpr and C57 mice with similar weights and sizes at 20-22 weeks old were selected. BMSCs were isolated using the whole bone marrow adherent method. Quantitative real-time polymerase chain reaction, β-galactosidase staining, western blotting, and ELISA were used to detect autophagy and senescence.

Result: Compared with BMSCs from normal mice, BMSCs from lupus mice exhibited low autophagy and premature senescence with a senescence-associated secretory phenotype. The addition of exogenous IL-6 increased the protein levels of p-STAT3 and Bcl-2, and in the IL-6-treated group, the premature senescence of cells increased and autophagy decreased.

Conclusion: The biological functions of BMSCs from MRL/lpr lupus mice were impaired. IL-6 prevents autophagy and subsequently promotes the senescence of BMSCs by activating the IL-6/STAT3 pathway.

Objective: To identify clusters of autoantibodies in a large cSLE population and to verify possible associations between different autoantibody clusters and the following variables: demographic data, cumulative clinical and laboratory manifestations, disease activity, cumulative damage and mortality. Methods: A cross-sectional study was performed in 27 Pediatric Rheumatology University centers, including 912 cSLE patients. The frequencies of seven selected autoantibodies (anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, aCL IgM and/or IgG and LA) were used for cluster analysis using the K-means method. Results: Four distinctive antibody clusters were identified. Cluster 1 (n = 322; 35.31%) was characterized by anti-dsDNA (61.18%), low frequency of antiphospholipid antibodies (<10%), and lower frequency of cutaneous, articular manifestation (p < 0.05) and hypocomplementemia (p < 0.001) compared to the other groups. Cluster 2 (n = 158; 17.32%) comprised anti-dsDNA (93.04%), aCL (87.34%) and LA (39.87%) and higher frequencies of thrombocytopenia (p = 0.006) and antiphospholipid syndrome (p < 0.001) than the other clusters. Cluster 3 (n = 177; 19.41%) was characterized by anti-dsDNA (81.36%), anti-Sm (100%) and anti-RNP (44.63%) antibodies, as well as a higher frequency of proteinuria compared to cluster 4 (58.15% vs 56.13% vs 64.00% vs 49.80%, p = 0.031). Cluster 4 (n = 255; 27.96%) consisted of all 7 autoantibodies, with predominance of anti-dsDNA (72.55%), anti-Ro/SSA (89.8%) and anti-La/SSB (45.88%), with no specific clinical pattern, except by higher pulmonary damage (p = 0.017). Conclusions:Our study suggests that, within the context of cSLE, the coexistence of anti-dsDNA with antiphospholipid autoantibodies is linked to an elevated incidence of antiphospholipid syndrome. This association does not coincide with a proportionate increase in the occurrence of nephritis. Conversely, the cluster of anti-dsDNA with anti-Ro/SSA and anti-La/SSB antibodies was associated with pulmonary damage, requiring close surveillance.