Lupus Science & Medicine最新文献

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.

Objectives: Neuropsychiatric SLE (NPSLE) lacks evidence-based treatment strategies. This study compared the effectiveness and safety profiles of obinutuzumab (OBZ) and rituximab (RTX) in patients with NPSLE.

Methods: Patients with new-onset NPSLE meeting British Isles Lupus Assessment Group grade A criteria who received either OBZ or RTX between 2018 and 2024 at Renji Hospital, Shanghai Jiao Tong University School of Medicine (with ≥12 months follow-up) were included. Propensity score matching (1:2 ratio) based on age, sex and SLE Disease Activity Index (SLEDAI) was performed. The primary outcome was complete or partial response at 12 months. Kaplan-Meier curves compared therapeutic effectiveness. Safety profiles of OBZ and RTX were recorded.

Results: 27 patients with new-onset NPSLE were included in this retrospective study, with 9 patients receiving OBZ and 18 patients receiving RTX. At 12 months, the primary outcome was achieved in 8 of 9 patients in the OBZ group and 13 of 18 patients in the RTX group (88.9% vs 72.2%; OR: 3.08, 95% CI 0.30 to 31.33; p=0.34). Compared with the RTX group, the OBZ group demonstrated higher lupus low disease activity state attainment (74.1% vs 52.3%; p=0.049), lower SLEDAI-2000 Scores (median (IQR): 2 (1-2) vs 4 (2-4.25); p=0.04) and a trend towards higher B cell depletion rates at 12 months (57.1% vs 20.0%; p=0.08). OBZ treatment significantly shortened hospitalisation by 7 days (14.7±5.4 vs 21.9±11.9 days; p=0.04) and achieved a deeper B cell depletion at 6 months (median CD19+B cells: 0.4 (0-1.4) vs 3.5 (2-19.3) cells/µL; p=0.01), compared with the RTX group. Safety profiles were comparable between groups, with both treatments well tolerated. No deaths occurred.

Conclusion: These findings suggest OBZ may induce superior clinical responses in NPSLE through enhanced B cell depletion, with acceptable safety at 12 months, calling for further exploration.

Objective: To investigate the pharmacokinetics, effectiveness, safety and tolerability of tofacitinib in young adults with active mucocutaneous (MC) SLE manifestations.

Methods: Patients with SLE and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) Activity (CLASI-A) Scores >8 newly received open-label tofacitinib from baseline to week (week) 72. Intensive pharmacokinetics sampling was done at the end of week 1, and safety was assessed throughout the study. The primary effectiveness endpoint was partial response of MC activity defined as <20% improvement of the CLASI-A Score from baseline (CLASI-PR) at week 8 in intention-to-treat analysis; secondary and other endpoints included MC complete response (CLASI-CR; CLASI-A=0) and quality of life (QoL) as measured by Skindex-29.

Results: Subjects were 11 patients (female patients: 10, mean±SD age: 23.0±5.87 years) with moderate to severe MC manifestations (CLASI-A=16.6±8.03). The pharmacokinetics of tofacitinib was comparable to that seen in juvenile and adult arthritis. During 629 patient-weeks of follow-up, 73 adverse events (AEs) were reported, none of which were considered severe or led to study discontinuation. There were three serious AEs (pelvic inflammatory disease, appendicitis and migraine with aura) but no major cardiovascular events, malignancies or death. In intention-to-treat analysis, at week 8 CLASI-PR was achieved in 73% (8/11) of subjects, in 82% at week 24 and 100% at week 72, respectively. Although CLASI-A Scores significantly decreased from baseline (baseline/week 8/week 24/week 72=16.55±8.03/8.64±7.8/8.82+7 .9/7+9.7; p<0.001), CLASI-CR was achieved by only <10% (1/11), starting week 8. Skindex-29 Scores improved significantly as early as week 4 (baseline/week 4/week 24/week 72= 37.6±24.16/26.1±23.58/24.3±28.67/25.5±30.71; p=0.009).

Conclusion: Tofacitinib in patients with SLE with active MC manifestations showed good effectiveness by week 4 as well as tolerability at exposure comparable to those with other rheumatic diseases. Tofacitinib was associated with significant improvement of QoL due to rapid improvement of MC inflammation. Observed safety and pharmacokinetics were comparable to observations in juvenile and adult arthritis.

Objective: To investigate the effects of Qihuang Jianpi Zishen Granules (QJZG) on renal injury in SLE mice, focusing on macrophage M1/M2 polarisation mediated by the AMPK/ULK1 signalling pathway.

Methods: Parameters of renal function and proteinuria were assessed. Pathological changes in the kidney were examined using H&E, periodic acid-Schiff and Masson's trichrome staining. Serum inflammatory factor levels were quantified using ELISA. The expression levels of the glycolysis rate-limiting enzymes hexokinase 2 (HK2) and glucose transporter 1 (GLUT1) were determined, and the transcriptional levels of AMPK/ULK1 pathway components were measured using quantitative PCR. The abundance of proteins associated with AMPK/ULK1 signalling was assessed via immunoblotting. Flow cytometry was used to quantify CD86+ M1 type and CD206+ M2 type macrophage populations. Dual immunofluorescence staining was employed to visualise F4/80+CD86+ and F4/80+CD206+ coexpression patterns.

Results: Compared with the Untreated group, mice in the PRED (prednisone acetate), QJZG and 2-Deoxy-D-glucose groups exhibited improved renal histopathology, reduced levels of creatinine, blood urea nitrogen, 24-hour RRO (24-hour urinary protein), ACR (Albumin-to-Creatinine Ratio), TPCR (Urine Total Protein-to-Creatinine Ratio), tumour necrosis factor alpha, interleukin (IL)-1β, IL-12, IL-23, IL-27, HK2, GLUT1, mTOR, CD86 and iNOS messenger RNA (mRNA), CD86 and iNOS proteins, M1 macrophages, M1/M2 macrophages and F4/80+CD86 expression (p<0.05). They also displayed increased expression of transforming growth factor-beta, IL-4, IL-10, C-C motif chemokine ligand 18, AMPK, ULK1, Atg13, CD206 and Arg-1 mRNA, AMPK, ULK1, CD206 and Arg-1 proteins, M2 macrophages and F4/80+CD206 (p<0.05).

Conclusion: QJZG effectively improved renal injury in SLE by reducing inflammation and modulating the AMPK/ULK1 signalling pathway to suppress M1 macrophage polarisation.

Objective: To determine whether subclinical brain dysfunction in SLE can be detected by disrupted interhemispheric connectivity and assess its modulation by immunosuppressive regimens.

Methods: 234 subjects (140 patients with SLE and 94 healthy controls (HCs)) were included. Through stratified analysis, patients with SLE were divided into treatment-naïve group (n=22), glucocorticoid monotherapy group (GC group, n=30) and GC combined with cyclophosphamide (CTX) and/or hydroxychloroquine (HCQ) treatment group (n=50) to assess the differences in voxel-mirrored homotopic connectivity (VMHC) between groups.

Results: SLE group showed lower VMHC than the HC group in bilateral superior temporal gyrus, medial superior frontal gyrus, calcarine fissure and surrounding cortex and middle occipital cortices (Gaussian random field corrected: voxel p<0.005, cluster p<0.01). The VMHC in the bilateral superior temporal gyrus (r_s=-0.250, p=0.024) and medial superior frontal gyrus (r_s=-0.246, p=0.026) was negatively correlated with the depression score, while the VMHC in the medial superior frontal gyrus was negatively correlated with the anxiety score (r_s=-0.239, p=0.031). Three SLE subgroups and HCs had different VMHC in the postcentral/precentral gyrus (F=8.942) and anterior cingulate/paracingulate gyrus (F=9.868). Post hoc analysis found that compared with the HC group, VMHC in the treatment-naïve group was decreased in the bilateral posterior central gyrus (t=-2.953), while in the GC monotherapy group, it decreased in the posterior central gyrus (t=-2.999) and anterior cingulate/paracingulate gyrus (t=-2.999). Compared with GC combined with CTX and/or HCQ group, VMHC in GC monotherapy group was decreased in the postcentral gyrus (t=-2.999).

Conclusion: Even without overt neuropsychiatric symptoms, patients with SLE exhibit impaired interhemispheric functional synergy that is partially reversed by combination immunosuppression, suggesting an early targetable brain pathway.