Lupus Science & Medicine最新文献

Objective: The question of sustained remission in SLE has been highlighted recently following data published on the use of chimeric antigen receptor-T cell therapy in SLE. With the review, we wanted to investigate the prevalence of sustained remission of 2 years or more in SLE with the current available treatments and to assess the predictive factors associated with this state.

Methods: A systematic review of Embase via Ovid and Medline via Ovid was performed. We considered articles of adult patients with SLE that report the prevalence and/or the predictive factors of sustained remission in SLE. We considered that the latter state is sustained if it was for 2 years or more.

Results: 20 studies were included for final review. The definition of remission was different between studies, and most authors considered different types of remission based on the serological activity and the current therapy. The prevalence of long-term remission was different across studies depending on the definition used. It ranged from 0.3% to 63%. Older age at diagnosis, lower disease activity at baseline and the absence of renal disease involvement were the most commonly found factors likely associated with sustained remission.

Conclusion: Long-term remission is an achievable state in SLE with current treatment. Studies report a striking heterogeneity in the current prevalences. This is likely to be caused by the lack of objective measures to confirm the state of sustained remission in SLE.

Background: Interstitial fibrosis in lupus nephritis (LN) is often infiltrated by immune cells but typically regarded as non-specific 'scar reaction'. This study aimed to investigate the relationship between inflammatory fibrosis and kidney disease progression in LN.

Methods: Interstitial fibrosis and tubular atrophy (IFTA) were scored in 124 LN kidney biopsies. Inflammation in areas of IFTA (i-IFTA) was graded 0-3 according to the Banff Classification of Allograft Pathology. Significant glomerular filtration rate (GFR) loss was defined as a decline of >15 mL/min at 3 years from biopsy. Immune cell phenotype was defined by serial immunohistochemistry (13-plex).

Results: IFTA was observed in 88/124 (71%) biopsies, and i-IFTA was identified in 76/88 (86%) cases. The distribution of i-IFTA grades was heterogeneous across all IFTA grades. In patients with moderate-to-severe IFTA (>25%), the degree of i-IFTA was associated with a higher risk of significant GFR loss: 0/1 (0%), 0/3 (%), 3/4 (75%) and 7/9 (78%) for i-IFTA grades 0, 1, 2 and 3, respectively (p=0.015). Multiplexed histology revealed that i-IFTA was mostly composed of CD163+ macrophages and CD4 T cells, followed by CD8 T cells and granulocytes.

Conclusion: I-IFTA is frequently observed in LN and is dominated by macrophages and T cells. For patients with baseline IFTA >25%, the degree of i-IFTA emerged as a predictor of GFR loss. These data support the routine scoring of i-IFTA in LN due to its prognostic implications and nominate i-IFTA as a potential therapeutic target.

Background: SLE is a chronic autoimmune disease with heterogeneous manifestations. This study evaluated the discriminative value of complete blood count-derived biomarkers, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), eosinophil-to-lymphocyte ratio (ELR), basophil-to-lymphocyte ratio (BLR), mean platelet volume and red cell distribution width (RDW), in identifying lupus flares.

Methods: This cross-sectional study was conducted over 10 years in the internal medicine department of Sahloul Hospital. SLE patients were classified by disease activity using Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K): flare (SLEDAI-2K >6) or remission (SLEDAI-2K ≤6). A matched group of healthy controls was included. Comparisons were made between flare/remission and flare/controls. Discriminative performance of biomarkers was evaluated using receiver operating characteristic analysis, with sensitivity (Se), specificity (Sp) and area under the curve (AUC) determined for the optimal cut-off values.

Results: The study included 83 SLE patients (40 flares, 43 remission) and 85 controls, median age of 32 years and a sex ratio of 0.16. Compared with remission, flares had significantly higher NLR and RDW and lower ELR. The most discriminative biomarkers were RDW (AUC=0.708, cutoff ≥14.65, Se =75.9%, Sp =60.6%), NLR (AUC =0.636, cutoff ≥2.63, Se =72.4%, Sp =51.5%) and ELR (AUC =0.647, cutoff ≤0.0076, Se =74.4%, Sp =65%). Compared with controls, flares showed higher NLR, PLR, MLR, RDW and lower ELR and BLR. Best performances were RDW (AUC =0.864, cutoff ≥13.85, Se =89.7%, Sp =75.3%), NLR (AUC =0.822, cutoff ≥2.28, Se =79.3%, Sp =76.5%) and ELR (AUC =0.775, cutoff ≤0.029, Se =87.1%, Sp =70.3%). SLEDAI-2K correlated positively with NLR (r =0.228), PLR (r =0.238), RDW (r =0.303) and negatively with ELR (r =-0.317).

Conclusions: These biomarkers may serve as simple, accessible and cost-effective tools for detecting lupus flares, particularly in resource-limited settings.

Introduction: SLE is a chronic autoimmune disease that is influenced by both genetic and environmental factors, one of which is diet. Dietary intervention plays a role in the management of SLE, and precision nutrition based on genetic data may enhance its effectiveness. The human leukocyte antigen (HLA)-DQ2 and DQ8 genotypes are strongly associated with coeliac disease (CD), and emerging evidence suggests a possible link between SLE and CD. However, no published studies have explored the use of HLA-DQ2 and DQ8 genotyping to guide dietary intervention in patients with SLE. This study aims to investigate the impact of dietary intervention, tailored to HLA-DQ2 and DQ8 genotyping, on disease activity and quality of life of patients with SLE.

Methods and analysis: 90 patients with SLE with positive HLA-DQ2 or DQ8 genotyping will be randomised in a 1:1 ratio to either the intervention group or a control group. Participants in the intervention group will receive intervention in the form of a low-gluten dietary modification for 12 weeks. Participants in both groups will continue their usual SLE medications. During three research visits (weeks 0, 4 and 12), all participants will complete a clinical interview, blood sample collection, dietary assessment and a questionnaire. Disease activity and quality of life will be assessed by the Mexican Systemic Lupus Erythematosus Disease Activity Index score and Lupus Quality of Life questionnaire. Other secondary outcomes that will also be assessed are fatigue score, sleep quality, anxiety and depression, and physical activity.

Ethics and dissemination: This study has obtained ethical approval from the Ethics Committee of the Faculty of Medicine, University of Indonesia-Cipto Mangunkusumo Hospital (KET948/UN2F1/ETIK/PPM0002/2025). Findings will be published in peer-reviewed journals and submitted for intellectual property rights.

Trial registration number: NCT07183007.

Objective: To evaluate the safety and efficacy of CD19 chimeric antigen receptor (CAR) T cell therapy in a patient with refractory lupus nephritis who experienced severe disease flare during immunosuppressive washout, and to assess whether pulse corticosteroid intervention affects CAR T cell therapeutic outcomes.

Methods: We report a single case of a 22-year-old woman with SLE and lupus podocytopathy refractory to multiple therapies including rituximab, belimumab and obinutuzumab. The patient was treated under single-patient IND (#30146) with autologous CD19 CAR T cells (KYV-101). During the preinfusion washout period, she developed severe lupus flare requiring pulse intravenous methylprednisolone. Clinical outcomes, CAR T cell expansion, B cell depletion and laboratory parameters were monitored before and after therapy.

Results: Despite experiencing severe lupus flare (fever, rash, arthritis, anti-dsDNA elevation, hypocomplementaemia) during washout, pulse methylprednisolone (250 mg intravenous, rapidly tapered) successfully controlled symptoms without compromising subsequent CAR T cell expansion (peak 15.5 cells/µL on day 7). The patient achieved sustained clinical remission with SLE Disease Activity Index Score decreasing from 17 prior to leukapheresis to 4 by week 17. At 12 months postinfusion, she remained in drug-free remission with stable kidney function and had returned to full-time work.

Conclusion: This case report illustrates that targeted pulse corticosteroids during CAR T cell therapy washout can effectively manage severe lupus flares without impairing therapeutic efficacy.

Objective: Lupus nephritis (LN) is a prevalent renal manifestation in patients with SLE, with kidney biopsy remaining the gold standard for evaluating disease activity. However, the invasive nature of biopsy and associated risks highlight the need for a non-invasive predictive tool. This study aimed to construct and validate predictive models for the activity index (AI) and tubulointerstitial lesions (TIL) in patients with LN as an alternative tool to assist clinicians in decision-making when kidney biopsy is not feasible.

Methods: We enrolled 266 patients with LN diagnosed by kidney biopsy from three centres, divided into a training cohort (n=213) and a validation cohort (n=53). Patients were stratified by AI and TIL scores: high AI (AI >4), low AI (AI ≤4), high TIL (TIL >4) and low TIL (TIL ≤4). Clinicopathological data were systematically collected. Multivariate logistic regression was employed to identify significant risk factors for high AI and TIL, and nomograms for individualised assessment were constructed. Model performance was evaluated using receiver operating characteristic curves, decision curve analysis, calibration plots and the Hosmer-Lemeshow test.

Results: The key independent risk factors for high AI included lymphocyte count, haematuria, albumin, serum creatinine, complement 4 and antihistone antibodies. For high TIL, the risk factors included age, haemoglobin, platelet count, blood urea nitrogen and antiribosomal P antibodies. Both nomograms demonstrated favourable performance in terms of discrimination and calibration across both cohorts.

Conclusion: The developed nomograms provide reliable, non-invasive tools for identifying patients with LN with high AI and TIL, which can improve clinical risk assessment and help guide more personalised management strategies.

Objectives: To identify antiphospholipid antibody-associated thrombocytopenia (aPLs-TP) phenotypes and assess their clinical outcomes.

Methods: This single-centre, prospective cohort study (January 2012 to April 2024) consecutively enrolled patients with aPLs-TP from Peking Union Medical College Hospital. Inclusion required persistent aPL positivity (≥12 weeks apart) and platelet (PLT) count <100×10⁹/L twice, excluding secondary causes. Demographic aPL profiles and clinical outcomes (thrombosis, pregnancy morbidity, microangiopathy and valve disease) were analysed. Hierarchical clustering and Kaplan-Meier survival analysis were performed.

Results: A total of 123 patients (65.9% female, mean age 36.0 years) were consecutively enrolled in the study. Median PLT count was 50.0×10⁹/L. Three clusters were identified: cluster 1 (n=35, all male, median PLT 67.0×10⁹/L) consisted of men with smoking history, hyperhomocysteinaemia and diabetes, demonstrating the highest rate of atherothrombotic and valvular events; cluster 2 (n=51, all female, median PLT 60.0×10⁹/L) included females with recurrent pregnancy morbidity and mild anaemia; and cluster 3 (n=37, 81.1% female, median PLT 27.0×10⁹/L) comprised patients with isolated severe thrombocytopenia with the lowest rate of complete remission. Analysis of event-free survival for key clinical outcomes differed significantly among clusters at 5 years (p=0.026): cluster 1 at 66.9% (95% CI 52.50 to 85.24), cluster 2 at 45.85% (95% CI 32.41 to 64.86) and cluster 3 at 88.68% (95% CI 78.80 to 99.80).

Conclusions: Significant heterogeneity exists in patients with aPLs-TP, thus making PLT count alone an inadequate predictor of clinical phenotypes and prognosis. Subgroup analysis leveraging distinct clinical features is essential to develop individualised treatment strategies and improve outcomes.

Objectives: This study examined if lowering the glucocorticoid (GC) ceiling in the definition of lupus low disease activity state (LLDAS) from 7.5 mg/day to 5 mg/day (LLDAS-5) was associated with better outcomes in patients with systemic lupus erythematosus (SLE).

Methods: Data from a 13-country longitudinal SLE cohort (American College of Rheumatology/Systemic Lupus International Collaborating Clinics criteria), collected prospectively between 2013 and 2020, were analysed. Survival analyses were used to examine the longitudinal associations of LLDAS definitions with flare, organ damage accrual (frailty models) and mortality (Cox regression models).

Results: 3801 patients with ≥2 visits were studied, with a median of 2.8 years (IQR: 1.0-5.4) of follow-up data (total visits: 40 949). 2141 (56.3%) patients experienced mild-moderate/severe flares; 717 (20.8%) accrued organ damage, and 80 (2.1%) died. 3072 (80%) patients attained LLDAS in 19 293 (47%) visits, while 2858 (75%) patients attained LLDAS-5 in 17 403 (42%) visits. Most patients in LLDAS were also in LLDAS-5; 214 patients (5.6%) attained LLDAS on at least one occasion, but never attained LLDAS-5. The magnitude of protection provided by LLDAS attainment against flare, irreversible organ damage accrual and mortality was similar with both GC thresholds. HRs (95% CIs) of damage accrual subsequent to spending 12 months in sustained LLDAS and LLDAS-5 were 0.42 (0.33 to 0.54, p<0.0001) and 0.43 (0.34 to 0.55, p<0.001), respectively. Likewise, HRs of flare and mortality corresponding to 12 months in LLDAS and LLDAS-5 were similar.

Conclusions: No evidence was found to support revising the GC dose threshold of the LLDAS definition. Regardless, minimising GC exposure remains a key goal of SLE management.

Trial registration number: NCT03138941.

Background: Immunogenicity to SARS-CoV-2 vaccination in patients with SLE varies by vaccine type and immune-modulating therapy. However, data in Southeast Asian populations, especially among Thai patients with SLE, remain limited.

Objective: To assess the levels of IgG response after the second dose of SARS-CoV-2 vaccination in Thai patients with SLE compared with healthy controls, and to explore factors associated with low immunogenicity to SARS-CoV-2 vaccine.

Methods: In this cross-sectional case-control study, adult Thai patients with SLE and age-matched and sex-matched healthy controls were enrolled following two SARS-CoV-2 vaccine doses under the Thai national immunisation programme. SARS-CoV-2 spike protein IgG was measured using electro-chemiluminescence immunoassay. Low immunogenicity was defined as IgG<15 U/mL.

Results: Among 92 patients with SLE and 41 controls, IgG levels were not significantly different (median: 221.3 vs 196.8 U/mL, p=0.41). The messenger RNA (mRNA) and viral vector vaccines yielded higher antibody levels than inactivated vaccines in patients with SLE. Factors such as active lupus nephritis and moderate-to-high dose corticosteroid use appeared to be associated with lower IgG responses, though not statistically significant.

Conclusions: Thai patients with SLE demonstrated an immune response comparable to that of healthy controls. A stronger immune response was observed in patients with SLE who received viral vector and mRNA vaccines, compared with those who received inactivated vaccines. Both vaccine type and disease-related factors may influence the magnitude of the immune response, emphasising the need for tailored vaccination strategies in this population.

Objective: Individuals with SLE commonly report chest pain or discomfort. We performed cardiovascular magnetic resonance (CMR) to differentiate coronary artery disease (CAD), coronary microvascular dysfunction (CMD), pericarditis and myocarditis in individuals with SLE who presented with chest symptoms. We also assessed the clinical utility of CMR.

Methods: Adults with SLE were included if reporting chest pain or dyspnoea suggestive of cardiac involvement to a rheumatologist between 2018 and 2023. Individuals underwent CMR, including quantitative myocardial perfusion mapping at rest and during adenosine stress if not contraindicated. CAD, CMD, pericarditis and myocarditis were identified by CMR. Confirmatory investigations were performed when indicated. We reviewed medical files to assess if CMR led to altered medical treatment or invasive interventions.

Results: Nineteen individuals with SLE (84% female) with a median age of 39 (IQR 31-55) years underwent CMR, of whom 14 (74%) were examined using adenosine stress. Symptoms prompting inclusion were pleuritic chest pain in 10/19 (53%), chest pain triggered by exercise or relieved by nitrates or rest in 2/19 (11%), other types of chest pain in 5/19 (26%) and dyspnoea suggestive of cardiac involvement in 2/19 (11%). CAD, CMD and pericarditis were diagnosed in 3/14 (21%), 2/14 (14%) and 3/19 (16%) individuals, respectively. None had myocarditis. CMR revealed no cause of chest symptoms in 12/19 (63%). The CMR results led to altered medical management in 6/19 (32%) individuals.

Conclusions: This cross-sectional study highlights cardiac ischaemia as a cause of chest symptoms in SLE. Notably, CAD and CMD were together more common than pericarditis and myocarditis. CMR may aid early detection and treatment of these conditions, as it altered medical management in one-third of cases. Larger studies are needed to confirm our findings and prospectively evaluate the long-term prognostic impact of early CMR in symptomatic individuals with SLE.