Lupus最新文献

Objective: To assess the impact of concomitant systemic lupus erythematosus (SLE) on the clinicopathological manifestations of thrombotic antiphospholipid syndrome (APS).

Methods: This single-centre, retrospective study compared clinical and antiphospholipid antibody (aPL) data from 118 patients, 58 with SLE-associated APS (SLE-APS), and 60 with primary APS.

Results: Median follow-up was 13.9 (IQR 7.7-19.3) and 8.6 years (3.5-10.6) for the SLE-APS cohort and PAPS cohort, respectively. Age at diagnosis of APS was lower in the SLE-APS cohort (mean 35.9 vs PAPS: 46.7 years; p < 0.05). Distribution of aPL subtypes was similar across cohorts. 198 thrombotic events were identified overall (index plus recurrent), with venous thromboembolism (VTE) and arterial thrombosis each occurring in just over half of patients in both cohorts. Microvascular thrombosis (12.1% vs 0%), and a mixed (any combination of venous, arterial and microvascular) thrombotic phenotype (19.0% vs 6.7%, p = 0.05) were more prevalent in SLE-APS patients. Recurrent thrombosis incidence rates (∼0.5 events/10-patient years), and Kaplan-Meier recurrence-free survival after index thrombosis, were similar. In the PAPS cohort, only: (i) triple-aPL-positivity was associated with a significantly higher recurrent thrombosis event rate (incidence rate ratio 2.22, p = 0.03) and lower recurrence-free survival after first thrombosis (log-rank test p = 0.01); (ii) lupus anticoagulant (LA)-positivity was associated with higher prevalance of arterial thrombosis (RR 2.69, p = 0.01), and lower prevlance of VTE (RR 0.48, p < 0.001), versus LA-negativity.

Conclusion: Concomitant SLE does not appear to modify long-term recurrent thrombosis risk, or aPL phenotypes, in patients with APS. Triple-aPL-positivity and LA-positive status may have less influence on thrombotic outcomes in patients with SLE-APS compared to PAPS.

Objective: Thalidomide is an effective medication for refractory mucocutaneous lesions of systemic lupus erythematosus (SLE) and can treat arthritis in some autoimmune diseases, but it has some adverse reactions. Recently, the effectiveness of tofacitinib in treating mucocutaneous lesions of SLE has been reported. We aimed to compare the efficacy and safety of tofacitinib with thalidomide in treating mucocutaneous and musculoskeletal lesions in patients with SLE.

Methods: This study was a real-world cohort study based on the Chinese SLE Treatment and Research group (CSTAR) registry. SLE patients who manifested mucocutaneous and/or musculoskeletal symptoms and were prescribed tofacitinib or thalidomide were included. We retrospectively conducted comparisons between the tofacitinib and thalidomide groups regarding clinical improvements, SLE disease activity, serological indicators, glucocorticoid doses, and adverse events at the 1, 3, and 6-months time points.

Results: At 3 and 6 months, the tofacitinib group exhibited a higher proportion of patients with improvement in mucocutaneous and musculoskeletal issues. Additionally, a greater percentage of patients in the tofacitinib group achieved remission or a low disease activity state (LLDAS) at these time points. No significant serological improvements were observed in either the tofacitinib or thalidomide groups. Fewer adverse events were observed in the tofacitinib group than in the thalidomide group.

Conclusions: Tofacitinib might be superior to thalidomide in the improvement of mucocutaneous and musculoskeletal lesions in SLE, and had a good safety profile.

Objective: Antiphospholipid syndrome (APS) is an autoimmune disease mainly affecting young individuals. Testing for antiphospholipid antibodies is recommended for young patients who are suspected to have APS. Yet, it is hard to differentiate APS from other acquired thrombophilia disorders in elderly-onset APS patients. This study aim to investigate the characteristics and prognosis of elderly-onset APS.

Methods: This is an observational cohort study. Thrombotic APS patients who underwent follow-ups between 2009 and 2022 were included. Elderly-onset APS patients (onset age ≥60 years) were compared to non-elderly-onset APS patients (onset age <60 years) and matched cases of elderly non-APS patients (age ≥60 years with thrombosis).

Results: A total of 161 APS patients were included in this study, 45 (28.0%) were elderly-onset APS. Stroke (35.6% vs. 18.1%, p = .018) was more common at disease onset in elderly-onset APS patients. Compared to non-elderly-onset patients, elderly-onset APS patients were associated with a higher number of cardiovascular risk factors. Elderly-onset APS patients showed significantly lower positive rate (51.1% vs. 71.6%, p = .014) and ratios [1.24 (1.01-1.38) vs. 1.37 (1.16-1.77), p = .004] of lupus anticoagulant. Elderly-onset APS patients had a significantly higher 10-years cumulative all-cause mortality (p < .001) and APS-related mortality than non-elderly-onset patients (p = .002) and elderly non-APS patients (p = .040).

Conclusions: Elderly-onset APS patients have unique disease characteristics with higher 10-years cumulative all-cause mortality and APS-related mortality. Early recognition and control of comorbidities may reduce the recurrence of thrombosis and mortality in elderly-onset APS patients.

Background and objectives: This study aimed to assess the utility of Doppler echocardiography in evaluating left ventricular diastolic function, and prognosis in patients with systemic lupus erythematosus (SLE).

Patients and methods: A total of 286 SLE patients were selected along with 100 age- and gender-matched healthy individuals who underwent physical examinations. Clinical baseline characteristics were collected. Various Doppler echocardiographic parameters were measured and analyzed, including left ventricular posterior wall thickness (LVPWT), interventricular septal diameter (IVSD), left ventricular mass (LVM), LVM index (LVMI), and others.

Results: Compared to the control group, SLE patients exhibited significantly higher levels of C-reactive protein and lower levels of complement (C) 3 and C4 (p < .001). Doppler echocardiographic parameters showed significant differences between SLE patients and healthy controls, including increased LVPWT, IVSD, LVM, LVMI, peak A, PWI + Tei, E/e', TDI-Tei, and decreased e' and E/A (p < .001). Subgroup analyses indicated more severe ventricular diastolic dysfunction in patients with higher SLE activity and those who experienced cardiovascular events. Correlation analysis revealed positive associations of PWI + Tei, TDI-Tei, and GLS with SLE activity and cardiovascular events (p < .01). Multivariate logistic regression analysis identified LVMI, PWI + Tei, TDI-Tei, and GLS as significant predictors of cardiovascular events (p < .05).

Conclusion: Doppler echocardiography is a valuable tool for the early diagnosis of left ventricular diastolic dysfunction in SLE patients. Key echocardiographic parameters, including LVMI, PWI + Tei, TDI-Tei, and GLS, are effective in predicting cardiovascular events, underscoring the importance of comprehensive cardiac function assessments in these patients.

Objectives: To assess the longitudinal effect of cyclophosphamide (CYC) treatment on type-I interferon (IFN) signature in proliferative lupus nephritis (LN) and its role in predicting treatment response.

Methods: Fifty-four biopsy proven proliferative LN patients scheduled to receive high-dose (HD) or low-dose (LD) CYC were recruited and followed up for six months. At six months, patients were classified as clinical responders (CR) or non-responders (NR) to treatment, using the EULAR/EDTA criteria. An IFN-gene based score (IGS) was developed from the mean log-transformed gene expression of MX1, OAS1, IFIT1, OASL, IFIT4, LY6E, IRF7 at baseline, three and six months. Longitudinal changes of IGS within and between groups were assessed and ΔIGS, which is the difference in IGS between baseline and three months was calculated. Independent predictors of non-response were identified and an ROC analysis was performed to evaluate their utility to predict NR.

Results: There was a dynamic change in IGS within the HD, LD, CR, and NR groups. Compared to baseline, there was a significant decrease in IGS at three months in HD and LD groups (HD group: 2.01 to 1.14, p = .001; LD group = 2.01 to 0.81, p < .001), followed by a significant increase from three to six months in LD group (LD: 0.81 to 1.51, p = .03; HD: 1.14 to 1.54, p = .300). A decrease in IGS from baseline to three months was seen in both CR (2.13 to 0.79, p < .001) and NR groups (1.83 to 1.27, p = .046), and a significant increase from three to six months was observed only in the CR group (CR: 0.79 to 1.57, p = .006; NR: 1.27 to 1.46, p = 1). ΔIGS (baseline to three months) was higher in CR compared to NR group (-1.339 vs -0.563, p = .017). ROC analysis showed that the model comprising of 0.81 fold decrease in IGS from baseline to three months, endocapillary hypercellularity and interstitial inflammation on renal histopathology predicted non-response with a sensitivity of 83.3% and specificity of 71.4%.

Conclusion: In proliferative LN, treated with HD or LD-CYC, combined model comprising of decrease in IGS score by 0.81 fold from baseline to three months, along with important histopathological features such as endocapillary hypercellularity and interstitial inflammation had better predictive capability for non-response.

Background: Neuropsychiatric systemic lupus erythematosus (NPSLE) is a poorly understood and heterogeneous manifestation of SLE. Common major NPSLE syndromes include strokes, seizures, myelitis, and aseptic meningitis. Easily obtainable biomarkers are needed to assist in early diagnosis and improve outcomes for NPSLE. A frequent end-result of major syndromes is neuronal or glial injury. Blood-based neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) have been utilized as markers for monitoring disease activity and/or severity in other neurodegenerative and neuroinflammatory diseases; however, they have not been evaluated in active major NPSLE.

Methods: This was a case-control study. We enrolled patients aged 12-60 years with active major NPSLE, SLE without active major NPSLE, and healthy controls. Active NPSLE was defined as being <6 months from last new or worsening neuropsychiatric symptom. Demographics, clinical data, and serum or plasma biosamples were collected.

Results: Thirteen patients with active major NPSLE, 13 age/sex/kidney function matched SLE controls without active major NPSLE, and 13 age/sex matched healthy controls (mean ages 26.8, 27.3, 26.6 years) were included. 92% of each group were female. Major syndromes included stroke (5), autonomic disorder (3), demyelinating disease (2), aseptic meningitis (2), sensorimotor polyneuropathy (2), cranial neuropathy (1), seizures (1), and myelopathy (2). Mean (standard deviation) blood NfL and GFAP were 3.6 pg/ml (2.0) and 50.4 pg/ml (15.0), respectively, for the healthy controls. Compared to healthy controls, SLE without active major NPSLE had mean blood NfL and GFAP levels 1.3 pg/ml (p = .42) and 1.2 pg/ml higher (p = .53), respectively. Blood NfL was on average 17.9 pg/ml higher (95% CI: 9.2, 34.5; p < .001) and blood GFAP was on average 3.2 pg/ml higher (95% CI: 1.9, 5.5; p < .001) for cases of active major NPSLE compared to SLE without active major NPSLE. In a subset of 6 patients sampled at multiple time points, blood NfL and GFAP decreased after immunotherapy.

Conclusions: Blood NfL and GFAP levels are elevated in persons with SLE with active major NPSLE compared to disease matched controls and may lower after immunotherapy initiation. Larger and longitudinal studies are needed to ascertain their utility in a clinical setting.

Objectives: Emerging evidence indicate that long noncoding RNAs (lncRNAs) may play an important role in the pathogenesis of systemic lupus erythematosus (SLE) however, the contribution of lncRNAs to SLE remains largely unclear. Our study aimed to explore the lncRNA expression profiles in peripheral blood mononuclear cells (PBMCs) from SLE patients.

Methods: LncRNA sequencing was used to detect differentially expressed genes in PBMCs from 5 SLE-MIX samples and 3 healthy controls (HC)-MIX samples, and the expression of selected lncRNAs was further verified by real-time quantitative polymerase chain reaction (RT‒qPCR). The correlation of lncRNA expression with laboratory indicators as well the SLE disease activity index 2000 (SLEDAI‒2K) score from 72 SLE patients was assessed by Spearman's test. The association between lncRNA ENST00000597482 and organ involvement in SLE patients was determined by the Mann‒Whitney U test. Moreover, lymphocyte subsets in peripheral blood from SLE patients were measured by flow cytometry. In addition, the diagnostic value of lncRNAs in predicting SLE was evaluated by receiver operating characteristic (ROC) curve analysis.

Results: The lncRNA expression profiles demonstrated 218 differentially expressed lncRNAs, including 121 upregulated genes and 97 downregulated genes, in PBMCs from SLE patients compared to HCs. Among the 10 candidate genes selected, only lncRNA ENST00000597482, which was lower in SLE PBMCs than in HCs, was consistent with the sequencing results. LncRNA ENST00000597482 expression was negatively correlated with SLEDAI-2K score and the titres of ANA antibodies and anti-double-stranded DNA (anti-dsDNA) antibodies. Of note, SLE patients with lower expression of lncRNA ENST00000597482 were prone to develop organ involvement. Furthermore, lncRNA ENST00000597482 exhibited potential diagnostic value in differentiating SLE patients from HCs.

Conclusions: LncRNA ENST00000597482 expression was lower in PBMCs from SLE patients than HCs and was negatively correlated with the SLEDAI-2K score and autoantibody titres. In addition, lncRNA ENST00000597482 could act as a novel biomarker for disease activity and diagnosis of SLE.

Background: Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease of undetermined etiology. Cardiac involvement is common in SLE and constitutes one of the main causes of mortality. More recently, new ultrasound imaging techniques, such as transthoracic ultrasound (TTE) with strain evaluation, have appeared and seem promising for the detection of cardiac involvement. The objective of our work was to study the frequency and characteristics of ultrasound abnormalities found in lupus patients and to study the benefit of ultrasound with global longitudinal strain (GLS) for early management.

Methods: It was an observational study of patients followed for SLE at the internal medicine and cardiology department of the HMPIT for 6 months (May-November 2023). The definition of cardiac involvement was by ultrasound. All patients benefited from TTE coupled with 2D-strain. We divided the workforce into two groups: the first group (patients with heart disease) and the second group (patients without heart disease).

Results: In a series of 40 lupus patients including 33 women and seven men, cardiac manifestations were reported in 60% of patients. In the first group, 29% had palpitations, 25% had chest pain, 67% had dyspnea, 37% had pericarditis, 8% had pulmonary arterial hypertension (PAH) and 12% had myocarditis. The comparative study showed that patients in the first group presented significantly more frequently with dyspnea (p = 0.02), chest pain (p = 0.03) and serositis (p = 0.01) compared to those in the second group. The mean left ventricular ejection fraction (LVEF) did not show a significant difference between the two groups. On the other hand, the average Global Longitudinal Strain (GLS) was significantly altered in the first group (p = 0.01). Furthermore, the frequency of pathological GLS was significantly higher in patients with lupus heart disease (p < 0.01).

Conclusion: Cardiac involvement during SLE is a frequent and most often asymptomatic complication. A systematic search for this impairment using a high-performance echocardiography examination, namely the 2D GLS, is essential for early treatment.

Objective: Substantial morbidity and mortality affect those with antiphospholipid antibodies (aPLs) and antiphospholipid syndrome (APS), yet patient experiences remain poorly understood. This research investigated patient experiences of aPL/APS diagnosis; effects on daily life; and healthcare and treatment.

Methods: Patients aged ≥18 years with APS per the Revised Sapporo criteria or with ≥1 positive aPL on ≥2 occasions were recruited from a Canadian multidisciplinary APS clinic to participate in semi-structured in-depth interviews. Interviews were conducted virtually and transcribed verbatim for subsequent thematic analysis.

Results: Twenty-one patients with aPLs/APS participated; 95.2% were female, mean (SD) age was 45.6 (15.0) years. Most (71.4%) had APS, and 71.4% had aPLs/APS with SLE. Results are presented around patient experiences of aPL/APS diagnosis, effects on daily life, and healthcare and treatment. Participants described medical complications/physical symptoms and the healthcare, lifestyle, and emotional impacts experienced around the time of aPLs/APS diagnosis. In addition to the physical and psychosocial impacts of living with aPLs/APS, patients reported modified leisure activities, altered employment trajectories, and positive and negative impacts on relationships. Impacts on family planning were also a critical component of the aPL/APS lived experience; participants shared experiences of miscarriage, other pregnancy complications, and medication-related challenges (e.g., with low-molecular-weight heparin injections). Challenging aspects of aPL/APS healthcare and treatment were also discussed, particularly related to the lifestyle, physical, and emotional burden of medication use. Although a lack of resources was described, participants expressed trust in healthcare providers when making management decisions or when seeking information. Suggestions for resources included the need for additional medication-related information, examples to help contextualize management behaviours, and additional information for those with aPLs/APS without SLE.

Conclusion: Patients highlighted how the diverse manifestations of aPLs/APS, accentuated by management-related challenges, impose considerable physical and psychosocial burdens. Results will inform the development of patient resources aligned with patient priorities.