Lupus Science & Medicine最新文献

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.

Background: Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterised by thrombosis, pregnancy complications and other non-thrombotic manifestations in the presence of antiphospholipid antibodies (aPL). Since its identification in 1983, research on APS has progressed, but no targeted therapies other than anticoagulation are yet available, with a mortality rate of 9.3% after a 10-year follow-up.

Objective: The aim of the current systematic literature reviews (SLRs) is to identify and compare upregulated proteins in patients with thrombotic APS (tAPS) and non-aPL thrombosis, thereby providing useful insights into APS pathogenesis.

Methods: We conducted two SLRs in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to identify proteins upregulated in tAPS and non-aPL-related thrombosis. Eligible studies included observational controlled research and focused on proteomics. Gene Ontology (GO) enrichment and network analyses were performed on the identified proteins.

Results: Of 108 and 209 records identified, seven and 13 were included in the SLR for tAPS and non-aPL thrombosis, respectively. The review identified 118 upregulated proteins in tAPS and 319 in non-aPL-related thrombosis. GO analysis revealed distinct biological process enrichment: platelet aggregation, platelet activation and blood coagulation were predominant in tAPS, while haemostasis, coagulation and wound healing were central in non-aPL-related thrombosis. Molecular functions in tAPS centred on receptor and protein complex binding, while enzymatic activities dominated in non-aPL thrombosis.

Conclusion: Our findings highlight the central role of platelet-related processes in tAPS pathogenesis, distinguishing it from non-aPL thrombosis. By elucidating the unique proteomic and functional characteristics of tAPS, this study provides a foundation for future research into targeted therapies that address platelet involvement in APS pathogenesis.

Objective: The left atrial stiffness index (LASI) has been proven to be a promising marker for assessing left atrial (LA) and left ventricular diastolic functions. This study aimed to evaluate the implication of LASI in diagnosing left ventricular diastolic dysfunction (LVDD) in patients with SLE.

Methods: 145 patients diagnosed with SLE were enrolled and subdivided into two groups based on the absence of concomitant lupus nephritis (LN). Additionally, a control group comprising 57 healthy volunteers was recruited. Speckle tracking echocardiography (STE) was performed in all participants. Conventional parameters and the LA strains were obtained, and LASI was calculated.

Results: (1) Patients with SLE presented significantly increased LA size and reduced function, with a significant increase in LASI, especially in those with concomitant LN. (2) LASI was positively correlated with age, interventricular end-diastolic septal thickness (IVSd) and E/e' (mitral E peak velocity to e' peak velocity) average, and negatively correlated with LA total emptying fraction (LATEF), LA passive emptying fraction (LAPEF), glomerular filtration rate (GFR), LA reservoir strain (LASr) and LA conduit strain (LAScd). Multivariate analysis showed that age, IVSd, maximum LA size and SLE activity index were independent determinants of LASI. (3) LASI demonstrated superior diagnostic performance for LVDD compared with E/e' average, LATEF, LASr and LAScd, with an area under the curve of 0.919.

Conclusions: LASI can effectively reflect changes in LA function in patients with SLE and provide superior diagnostic accuracy compared with other parameters and LA strains for LVDD. Therefore, LASI could be a potential marker for the early detection of LVDD in patients with SLE.