This study aims to determine the effects of sleep quality along with age, marital status, socioeconomic status, depression, anxiety, disease activity, pain scale, and dose of corticosteroids on quality of life in women with SLE. Variables were assessed in 75 women with SLE using the Pittsburgh Sleep Quality Index (PSQI), Lupus Quality of Life (Lupus QoL), Depression, Anxiety, and Stress Scale-21 (DASS-21), and Mexican SLE Disease Activity Index (MEX-SLEDAI). Bivariate and multivariate analyses were performed to determine contributors to quality of life. Of 75 subjects, 35 (46.7%) patients had poor sleep quality. The mean QoL score for patients is 84.27. Poor sleepers had impaired QoL in physical health (p = 0.003), emotional health (p = 0.007), pain (p = 0.003), and planning (p = 0.006), with fatigue (p < 0.0001) as the most significantly impaired. Younger age (Mean ± SD = 81.1 ± 12.67; p = 0.014) and anxiety or depression (Mean ± SD = 56.66 ± 8.17; p = 0.006) were significantly associated with lower quality-of-life scores. The linear regression results showed an R-squared of 0.361, with anxiety (β = 21.402), sleep quality (β = 8.392), and age (β = 5.526) as the most significant variables. Marital status, socioeconomic status, disease activity, pain scale, and corticosteroid dose did not correlate with QoL. Poor sleep quality, anxiety, and younger age were significant independent predictors of lower QoL in women with SLE, explaining 36.1% of the variance. These findings suggest that psychosocial and sleep interventions are crucial for improving well-being in this population, potentially more so than focusing solely on disease activity.

ObjectivesTo describe clinical outcomes after switching to anifrolumab in patients with systemic lupus erythematosus (SLE) who showed inadequate response to belimumab, and to explore clinical features potentially associated with treatment response in real-world settings.MethodsWe retrospectively reviewed the cases of eight patients with SLE who were switched from belimumab to anifrolumab because of insufficient clinical response. Clinical data, including the SLE Disease Activity Index 2000 (SLEDAI-2K), serological markers, organ involvement, medication use, and attainment of a lupus low disease activity state (LLDAS), were descriptively evaluated.ResultsAll eight patients were female; most were young and had active mucocutaneous manifestations. Three patients presented with cutaneous vasculitis and one with panniculitis. Three patients had neuropsychiatric manifestations, including mood disorders or cerebrovascular disease, and one patient had membranous lupus nephritis. Following anifrolumab initiation, clinical improvement was observed predominantly in skin and neuropsychiatric manifestations, whereas renal involvement showed limited improvement. Improvements in SLEDAI-2K scores, complement levels, and glucocorticoid dose reduction were observed in most patients. Five patients achieved LLDAS during follow-up. Clinical improvement was more frequently observed among younger patients and those with active skin manifestations and anti-ribonucleoprotein antibody positivity.ConclusionsIn this exploratory case series, switching from belimumab to anifrolumab was associated with clinical improvement among selected patients with SLE. Certain clinical features, including active skin or neuropsychiatric manifestations and anti-ribonucleoprotein antibody positivity, were more frequently observed among patients who showed improvement after switching therapy. These findings should be interpreted as hypothesis-generating and warrant confirmation in larger prospective studies.

To estimate the prevalence of active kidney involvement and its associations with comorbidities and treatment patterns among patients with systemic lupus erythematosus (SLE) at renewal application for the Designated Intractable Diseases of Japan. We analyzed Medical Certificates of Designated Intractable Diseases that were submitted in 2016 for the renewal of SLE designation. Among 35,207 digitized patients (mean age, 51.1 ± 15.7years), active kidney involvement was defined as proteinuria (≥ 0.5g/day) and/or urinary casts (granular casts or red blood cell casts) recorded as Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) items during the 6months preceding the renewal application. Active kidney involvement was identified in 8273 patients (23.5%). Compared with those without active kidney involvement, patients with active kidney involvement had a younger mean age at disease onset (32.6 ± 15.3 vs. 34.1 ± 15.2years) and a lower proportion of females (84.3% vs. 90.5%). They more frequently had comorbid infection (14.6% vs. 10.6%), diabetes mellitus (16.2% vs. 11.2%), and hypertension (43.6% vs. 25.6%), and had higher disease activity (mean SLEDAI, 14.8 ± 9.4 vs. 7.0 ± 6.4). Glucocorticoid use was more common (94.9% vs. 91.8%), fewer patients received ≤ 7.5mg/day (45.9% vs. 59.2%), and concomitant immunosuppressant use was higher (60.8% vs. 44.1%). Approximately one-quarter of Japanese patients with SLE undergoing renewal had active kidney involvement, which was associated with higher disease activity, more comorbidities (notably hypertension), and greater use of glucocorticoid and immunosuppressants.

To identify factors associated with adverse outcomes in Korean patients with systemic lupus erythematosus-associated pulmonary arterial hypertension (SLE-PAH) confirmed by right heart catheterization (RHC). This multicentre retrospective study included 68 patients with SLE-PAH diagnosed by RHC at eight tertiary centres. Baseline demographic, clinical, laboratory and haemodynamic data were collected, along with SLE Disease Activity Index (SLEDAI) scores and PAH-related parameters. Primary endpoint was a composite outcome of worsening PAH symptoms requiring treatment escalation, lung transplantation, death or hospitalization. Univariable and multivariable logistic regression analyses were performed to identify independent predictors. Of 68 patients, 35 (51.3%) experienced composite outcomes. Compared with those without composite outcomes, patients with composite outcomes had significantly shorter baseline 6-min walk distances (P = 0.024), higher tricuspid regurgitation velocity (P = 0.032), higher right ventricular systolic pressure (P = 0.035), higher mean pulmonary arterial pressure (mPAP) (P < 0.001), higher mean physician global assessment scores (P = 0.001), higher mean SLEDAI scores (P = 0.005) and more frequent use of combination PAH therapy (P = 0.033). In multivariable analysis, elevated mPAP (odds ratio (OR) 5.401; 95% confidence interval (CI) 1.129-25.837, P = 0.035), higher SLEDAI (OR 5.495; 95% CI 1.041-29.012, P = 0.045) and combination PAH therapy (OR 1.695; 95% CI 1.015-3.267, P = 0.017) remained independent predictors of composite outcomes. Elevated mPAP, active lupus and use of combination PAH therapy were independently associated with poor outcomes in SLE-PAH, highlighting the relevance of comprehensive haemodynamic assessment and careful management of lupus activity.

This study aimed to explore the clinical characteristics of patients with lupus myocarditis (LM) and to evaluate the efficacy of rituximab (RTX) in LM treatment. The medical records of all patients with LM admitted to our hospital between January 2012 and March 2025 were retrospectively analyzed. Two control groups were established by randomly matching patients by sex and age at a 1:1 ratio: patients with systemic lupus erythematosus (SLE) without LM and patients with non-SLE myocarditis. The SLE disease activity index 2 K (SLEDAI 2 K) score and Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS) were calculated to evaluate SLE disease activity. A total of 22 patients with LM were enrolled. Patients with LM had a higher incidence of lupus nephritis and a higher positivity rate for anti-SSB antibodies than those with SLE without LM. Furthermore, patients with SLE with LM had significantly higher SLE-DAS than those without LM, although no statistical difference in SLEDAI 2 K score was observed between the groups. Wall motion abnormalities, valvular regurgitation, and decreased left ventricular ejection fraction (LVEF) were more frequent in patients with LM than in those with non-SLE myocarditis. All patients with LM received corticosteroid treatment, with three of them receiving RTX in addition to standard therapy. With a median follow-up of 4 (range, 1-24) months, 2 patients (9.1%) died due to heart failure, and the remaining 20 achieved symptom remission. Moreover, 13 patients underwent follow-up echocardiography, which showed a significant improvement in LVEF. The three patients treated with RTX achieved clinical improvement within a mean of 2 weeks, enabling rapid glucocorticoid tapering. Patients with LM more frequently present with lupus nephritis and positive anti-SSB antibodies, are more likely to have echocardiographic abnormalities, and exhibit a higher mortality rate. In addition, RTX is a promising drug for LM treatment.

ObjectiveBelimumab, a B-cell modulator, targets the central immunopathogenic pathway in systemic lupus erythematosus (SLE) by selectively inhibiting B lymphocyte stimulator (BLyS) and reducing the autoreactive B cells that drive disease activity. Its effectiveness in reducing disease activity and its steroid-sparing potential have been well-documented in both clinical trials and real-world studies. This study evaluated belimumab's long-term effectiveness in reducing oral glucocorticoid (OGC) use based on updated European Alliance of Associations for Rheumatology (EULAR) recommendations, and in attaining low disease activity and remission in adults with SLE.MethodsThis post hoc descriptive analysis (GSK Study 219649) utilized pooled data from individual OBSErve studies conducted in eight countries, collected at belimumab initiation and 6 months (all countries), and 6 to 24 months (USA and Argentina) post-initiation. Endpoints included percentages of patients achieving ≤5mg/day OGC; maintaining 0 and ≤5mg/day OGC beyond 6 months; attaining low disease activity (modified Lupus Low Disease Activity State [mLLDAS]: SLE Disease Activity Index [SLEDAI] score ≤4, OGC dose ≤7.5mg/day) and remission (modified Definition Of Remission In SLE [mDORIS]: SLEDAI score = 0, OGC dose ≤5mg/day) over time. The sample size in this study was fixed by available data from the OBSErve studies.ResultsData from 959 patients were included (mean [SD] age: 41.5 [12.4] years; 89.5% female; 52.2% from the USA). Of patients prescribed OGC at index, percentages receiving ≤5mg/day increased from 16.1% at belimumab initiation to 51.6% at 6 months and 87.5% at 24 months; 8.2% discontinued OGC at 6 months and 44.4% at 24 months post-initiation. Of patients achieving 0 and ≤5mg/day OGC at 6 months, 87.9% and 92.9% maintained this dose for 24 months. Percentage attaining mLLDAS/mDORIS increased from 0.4%/0.2% at belimumab initiation to 11.1%/7.4% at 6 months and 18.2%/12.9% at 24 months post-initiation.ConclusionsThese results from a real-world clinical setting suggest that belimumab treatment supports patients in achieving EULAR-recommended OGC taper goals, with sustained OGC dose reductions observed alongside an increased percentage of patients attaining low disease activity and remission as early as 6 months following belimumab initiation.

ObjectiveTo compare patients with SLE associated with either Evans syndrome (ES) or an isolated autoimmune cytopenia (immune thrombocytopenia (ITP) or autoimmune haemolytic anaemia (AIHA)).MethodsMulticentre retrospective study including patients with SLE presenting with ITP, AIHA or ES of clinical significance (ie, requiring therapeutic intervention according to European Alliance of Associations for Rheumatology guidelines or clinician discretion). Clinical, laboratory and outcome data were compared between patients with ES and those with ITP or AIHA. Severe SLE flares were defined as flares with SLE Disease Activity Index ≥10.ResultsAmong 95 patients with SLE included, 30 had ES, 43 ITP and 22 AIHA. The number of severe SLE flares per patient was higher in ES than in ITP (1.3 vs 0.4, p=0.0004) and patients with AIHA (0.4, p=0.006). Patients with ES had a higher incidence rate ratio (IRR) of severe SLE flares (IRR =3.03; 95% CI 1.50 to 6.41), which remained significant in inverse probability of treatment weighting analyses. At last follow-up, patients with ES presented higher rates of renal (36.7% vs 9.3%, p=0.007) and neurological (36.7% vs 11.6%, p=0.019) involvement than patients with ITP. Severe infections were more frequent in patients with ES than ITP (47% vs 23%, p=0.045), with a higher mean number of severe infections per patient (1.2 vs 0.5, p=0.04).ConclusionIn patients with SLE, ES is associated with an increased risk of severe flares than isolated autoimmune cytopenia. These findings were consistent after adjustment for baseline imbalances, supporting ES as a high-risk SLE phenotype.

ObjectivesFatigue is one of the most common and debilitating symptoms experienced by patients with systemic lupus erythematosus (SLE). Previous studies revealed the association of fatigue with various SLE and non-SLE-related factors. This study aims to explore the prevalence of fatigue and the factors that are associated with fatigue experienced by SLE patients in an outpatient rheumatology clinic setting.DesignProspective, observational study using a sample of convenience.SettingOutpatient rheumatology clinic at a tertiary care centre.ParticipantsConsecutive subjects with SLE presenting for their outpatient visits enrolled in the ongoing Institutional Review Board-approved ‘Pathogenesis and Natural History of SLE’ protocol.Primary and secondary outcome measuresDisease activity and organ damage accrual were measured by Safety of Estrogens in Lupus Erythematosus: National Assessment Version of the Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI), respectively. Fatigue was measured by the self-reported Fatigue Severity Scale (FSS), and a score of ≥4 was used to define clinically significant fatigue. Correlation analyses were done to determine the association between fatigue and patient demographics, and SLE disease activity and damage indices. Results were considered as statistically significant at p<0.05. All data analyses were carried out with the SAS program, release V.9.4 (SAS Institute).Results183 patients completed the study, with a significant proportion (144/183) belonging to ethnic minorities. The overall FSS score was mean (±SD) 4±1.8 and SELENA-SLEDAI score of 3±2.6. The group reporting significant FSS scores ≥4 (N=95) included a higher proportion of White patients, more organ damage (SLICC/ACR DI score mean (±SD) 1.9±1.9) and higher body mass index (BMI) mean (±SD) 29.6±6.7 kg/m2; as compared with the group with FSS scores <4(N=85), which had a higher proportion of Black patients (p=0.034), lower SLICC/ACR DI scores (1.1±1.3 (p=0.008)) and BMI 27.6±5.6 kg/m2 (p=0.03).ConclusionsOur study found that organ damage accrual, specifically pulmonary fibrosis and neuropathy as measured by SLICC-ACR DI and high BMI, is associated with clinically significant fatigue in SLE. Furthermore, our results support previous findings that fatigue is independent of SLE disease activity. Findings of our study need to be replicated in independent SLE cohorts measuring fatigue at multiple time points. Mechanistic studies are needed to better understand pathogenesis of fatigue in SLE.

Erythrocyte sedimentation rate (ESR) is one of the most commonly used markers of inflammation in clinical practice. However, its value in predicting disease behavior in patients with systemic lupus erythematosus (SLE) remains controversial. The aim of this study was to determine the clinical significance of ESR in a large cohort of Chinese patients with SLE. Data of 1,217 patients with documented ESR values were extracted from a lupus database collected by Jiangsu Lupus Collaborative Group. The associations of ESR with diverse manifestations, disease activity, damage accruement, and concurrent infection status were evaluated using logistic regression, and receiver operating characteristic (ROC) curve analysis was performed to determine the optimal cutoffs for ESR and the C-reactive protein (CRP)/ESR ratio. The prognosis of patients with normal and high ESR was assessed using Kaplan-Meier analysis. Of the patients in this cohort, 81.0% had increased ESR values. ESR elevation was independently associated with fever (OR = 1.664, 95%CI = 1.072-2.583), serositis (OR = 2.005, 95%CI = 1.105-3.64), interstitial pneumonia (OR = 3.394, 95%CI = 1.176-9.796), hypoalbuminemia (OR = 1.536, 95%CI = 1.076-2.193), and anemia (OR = 3.102, 95%CI = 2.213-4.348). Compared with the damage accrual score [the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI)], there was a stronger correlation between the ESR value and the SLE Disease Activity Index (SLEDAI) score, and a value not less than 25 mm/h helped to define disease activity with high sensitivity. The increase of ESR was much slower than that of CRP at the time of infection, and a CRP/ESR ratio ≥0.5 had high specificity to depict the presence of infection. The 5- and 10-year survival rates of patients with elevated ESR values were worse than those with normal values. This study suggests that ESR is not only related to disease activity and prognosis but also to the patient's autoimmune status. The CRP/ESR ratio helps distinguish the presence of infection in patients with SLE.

Baricitinib is a JAK1 inhibitor that showed efficacy in patients with systemic lupus erythematosus (SLE) in a phase 2 study but failed to meet the primary endpoint in phase 3 trials. To understand this discrepancy and identify patients with SLE who are responsive to baricitinib, we conducted baseline and longitudinal transcriptomic analysis in patients enrolled in the phase 2 trial. Whole-blood samples from 272 patients with SLE were analyzed. Clinical response was assessed using SLE Responder Index-4 after 24 weeks of placebo or baricitinib (2 or 4 mg daily). Gene expression profiling was conducted using Gene Set Variation Analysis (GSVA) of 32 immune-related gene modules. Eight distinct molecular endotypes (A-H) were identified from baseline GSVA scores, with progressively increasing immune disturbances. Baseline demographics were similar across endotypes, with modest but significant differences in anti-double-stranded DNA and complement levels but no SLE Disease Activity Index differences. Significant clinical responses to baricitinib were confined to endotypes D and G (P = 0.004 and 0.048 vs placebo, with effect sizes of 41.54% and 31.89%, respectively). Importantly, patient clustering based on clinical features failed to identify treatment-responsive subsets. Endotype G demonstrated the most pronounced treatment-related transcriptional modulation, with dose-dependent suppression of interferon, JAK1/JAK2/TYK2 signaling, immunoproteasome, and inflammatory pathways evident as early as week 2 and sustained through week 24. Transcriptional changes in response to baricitinib were largely confined to clinical responders in endotype G. Feature importance analysis identified the interferon and Treg cell signatures as major predictors of response. Transcriptomic analysis identified subsets of patients with SLE responsive to baricitinib.

ObjectiveTo develop and validate a novel SLE disease activity scoring model designed to enhance diagnostic capability for moderate-to-severe disease activity in SLE patients compared to the SLE Disease Activity Index 2000 (SLEDAI-2K).MethodsAll 1163 SLE patients from Shandong Provincial Hospital and the Affiliated Hospital of Qingdao University constituted the derivation cohort, while another 323 patients from Shandong Provincial Hospital served as the validation cohort. Disease activity was assessed for each patient using the Physician Global Assessment (PGA) and SLEDAI-2K. With PGA-defined moderate-to-severe SLE activity as the dependent variable, binary logistic regression analysis identified factors influencing disease activity and constructed a regression model. Receiver operating characteristic (ROC) curve analysis evaluated the model’s discriminative ability. Correlations between the new scoring model, PGA, and SLEDAI-2K were examined.ResultsBinary logistic regression identified 25 clinical manifestations as independent risk factors for higher SLE activity (all P<0.05): neuropsychiatric symptoms, visual impairment, vasculitis, arthritis, myositis, hematuria, proteinuria, pyuria, alopecia, rash, mucosal ulcers, pleurisy, pericarditis, hypocomplementemia, elevated anti-dsDNA, fever, thrombocytopenia, leukopenia, pulmonary hypertension, hypothyroidism, hypocalcemia, lymphadenopathy, abnormal liver function, high-titer ANUA. Using the 25 variables listed above, we constructed a new scoring model. ROC analysis for distinguishing moderate-to-severe activity showed areas under the curve of 0.972 (95% CI: 0.963-0.980, P<0.001) in the derivation cohort and 0.971 (95% CI: 0.958–0.985, P<0.001) in the validation cohort.ConclusionTwenty-five clinical manifestations were identified as independent risk factors for assessing moderate-to-severe SLE activity. The resulting model demonstrated enhanced accuracy in identifying moderate-to-severe disease activity states.

Lupus nephritis (LN) is a common and severe manifestation of systemic lupus erythematosus (SLE). We sought to evaluate treatment patterns, treat-to-target state attainment, and outcomes of patients with active LN on non-biologic, conventional therapy, in a large real-world cohort from the Asia–Pacific region. Adult patients enrolled in a multinational lupus cohort were studied for evidence of active LN, defined based on the SLE Disease Activity Index-2000 (SLEDAI-2K)-proteinuria threshold (> 0.5 g/24 h or > 0.05g/mmol), ≥ 2 visits of data, and no exposure to biologics. The subset of these patients who had kidney biopsy-confirmed LN was retrospectively determined. Attainment of treatment goals, including modified versions of complete renal response (mCRR) and primary efficacy renal response (mPERR), lupus low disease activity state (LLDAS) and DORIS remission (REM), and organ damage accrual, were assessed over time following the first visit with proteinuria. One thousand one hundred eighty patients were studied for a median 2.7 [IQR 1.0, 5.0] years, 435 (37%) of whom had biopsies (Class III/IV = 242 (56%)). mCRR, mPERR, LLDAS, and REM were attained at least once during follow-up by 46%, 55%, 60%, and 46% of patients, respectively. mCRR and mPERR attainment was highest at year 2, while LLDAS and REM attainment gradually increased over time. New organ damage accrued in 11% of patients by year 1, increasing to 33% by year 5. In a multinational cohort of patients with active LN receiving non-biologic conventional therapy, the attainment of renal responses, LLDAS, and REM was low, while damage accrual was prevalent.

ObjectiveA retrospective cohort study to analyze the effectiveness and safety of belimumab using in the initial treatment of childhood-onset systemic lupus erythematosus (cSLE).MethodsWe collected clinical data from all children with a first diagnosis of cSLE admitted to our center between 1 April 2021 and 1 November 2024. Patients who initiated belimumab within 1 month of diagnosis were assigned to the belimumab group, and those who did not receive belimumab comprised the control group. Propensity score matching (PSM) was applied to balance baseline characteristics between the groups. The proportion of lupus low disease activity status (LLDAS) and remission (Definitions of Remission in Systemic Lupus Erythematosus, DORIS), the disease activity scores, laboratory tests, glucocorticoid dosage, and adverse effects during the courses of treatment in two groups were analysis.ResultsThere were 39 cases in both the belimumab group and the control group. The belimumab group exhibited a higher proportion of patients achieving LLDAS (31/39 vs. 14/39, p < 0.001) and DORIS (18/39 vs. 5/39, p =0.002) compared to the control group at 12 months after treatment. Additionally, the time to achieve LLDAS and DORIS was significantly shorter in the belimumab group (log-rank p< 0.001). However, no statistical variances were observed between the two groups in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, physician global assessment (PGA) scores, complement levels, negative rates of anti-double-stranded DNA (anti-dsDNA) antibodies at each follow-up interval. From the 7th to the 12th month of treatment, the daily prednisone dose in the belimumab group was lower than in the control group. After 12 months of treatment with belimumab, B cells (p< 0.001) and immunoglobulin G (IgG) (p< 0.001) showed a significant decrease from baseline. No infusion-related adverse reactions were observed in children receiving belimumab, and the infection rate did not differ significantly from the control group.ConclusionsAdding belimumab to initial therapy facilitates quicker disease control and expedites glucocorticoid tapering in children, which can be a new treatment strategy for cSLE.

ObjectiveChildhood-onset systemic lupus erythematosus (cSLE) exhibits significant heterogeneity, leading to challenges in prognosis and treatment. This study aims to stratify cSLE patients into clinically distinct subgroups based on routine autoantibody profiles and to characterize these subgroups by their differences in HLA-DRB1 genotypes, cytokine signatures, clinical manifestations, and flare incidence.MethodsWe conducted a retrospective study of 102 cSLE patients. An unsupervised two-step cluster analysis was performed using nine routinely measured autoantibodies. The resulting subgroups were compared for clinical features, HLA-DRB1 allele frequencies, serum cytokine levels, and flare-free survival using Kaplan–Meier analysis.ResultsCluster analysis identified two distinct subgroups. Subgroup 2, characterized by anti-Sm/RNP positivity, demonstrated significantly more severe disease, including higher rates of lupus nephritis, neuropsychiatric involvement, and elevated SLE disease activity index (SLEDAI) scores at diagnosis compared to subgroup 1 (anti-Sm/RNP-negative). Genetically, subgroup 2 was enriched with the HLA-DRB1*15 and *09 alleles. Immunologically, subgroup 2 exhibited significantly elevated IFN-α levels. Despite more frequent use of belimumab, subgroup 2 had a significantly lower flare-free survival rate than subgroup 1 (P < 0.001).ConclusionAutoantibody-based stratification effectively delineates two cSLE subgroups with distinct genetic, immunological, and clinical trajectories. The anti-Sm/RNP positive subgroup, defined by HLA-DRB1*15/09 risk alleles and a high IFN-α signature, represents a more severe phenotype with a higher risk of flare, potentially explaining the suboptimal response to belimumab in this group.

This study aimed to determine whether interferon regulatory factor 5 (IRF5) activation and its temporal dynamics in immune cells correlate with disease activity and flares in patients with systemic lupus erythematosus (SLE). Patients with SLE were prospectively enrolled and followed up for 52 weeks. The IRF5 nuclear translocation rate (NTR) was assessed in monocytes, dendritic cells, and B cells during baseline and follow-ups. Associations among IRF5 NTR, disease activity, and flares were statistically analyzed. Of 40 patients enrolled, 27 were included in the analysis after meeting all inclusion criteria. Baseline IRF5 NTR in B cells was correlated with SLE disease activity index scores (r = 0.529, p = 0.005). Nineteen patients developed flares, and high baseline IRF5 NTR showed good predictive accuracy (AUC = 0.763) and an increased flare risk (OR = 25.5, p = 0.003). In survival analysis, patients with high IRF5 NTR had significantly shorter flare-free survival (log-rank p = 0.030) and higher hazard of flare (HR = 7.43, p = 0.010). IRF5 NTR further increased during the 12 weeks preceding flares (p = 0.040). The IRF5 NTR in B cells is a potential biomarker for disease activity and flare prediction in SLE.

Lupus retinopathy (LR) is one of the most frequent and serious ocular complications of systemic lupus erythematosus (SLE), because it may cause irreversible visual impairment. The aim of this study was to evaluate the association between serum anti-retinal antibodies levels of SLE patients and the incidence of LR. Levels of serum anti-α-enolase antibody (Ab), anti-arrestin Ab, anti-recoverin Ab and anti-IRBP3 Ab were detected in 89 SLE patients (divided into LR group and non-LR group) and 81 healthy controls by enzyme-linked immunosorbent assay (ELISA). The correlation between these four anti-retinal Ab, SLE activity and the incidence of LR was evaluated. LR group had a higher SLE disease activity index (average SLEDAI score, 18 (7) versus 9 (5), P < 0.001), higher frequency of pleurisy (40% versus 20.4%, P = 0.044) and lower level of hemoglobin (102.343 ± 23.157 versus 112.759 ± 19.678, P = 0.025) comparing to non-LR group. LR group had higher levels of anti-α-enolase than non-LR group (P = 0.033) and control group (P < 0.0001). The levels of anti-recoverin in LR group was higher than non-LR group (P = 0.036) and control group (P < 0.0001), while the difference was not significant between non-LR group and control group (P = 0.109). Using combination of anti-α-enolase Ab and anti-recoverin Ab to diagnose LR in SLE patients is more effective (with area under the receiver operating characteristic curve (AUC): 72.68%) than use anti-α-enolase Ab (AUC: 65.65%) or anti-recoverin (AUC: 61.96%) only. Our results suggested that anti-α-enolase and anti-recoverin may be used as potential biomarkers of lupus retinopathy in SLE patients.

Systemic lupus erythematosus (SLE) is an autoimmune disorder characterised by multisystem involvement, frequently including cardiovascular manifestations. Interleukin 2 (IL-2), a key cytokine in immune regulation, plays a pivotal role in maintaining tolerance by promoting regulatory T cell function. The relationship between serum IL-2 levels and specific SLE features remains incompletely defined. The aim of our study was to investigate the associations between serum IL-2 concentrations and disease activity, inflammatory markers, autoantibody profiles as well as cardiovascular and metabolic parameters in a well-characterised cohort of patients with SLE. In this cross-sectional study, 235 patients with SLE were recruited and characterised, including assessment of autoantibody profiles, disease activity indices (SLE Disease Activity Index-2000 (SLEDAI-2K)), Damage Index and remission status. Cardiovascular characteristics were evaluated, encompassing lipid profiles, insulin resistance indices and carotid ultrasound parameters such as plaque presence, intima-media thickness and arterial stiffness. Serum IL-2 concentrations were quantified using an ultrasensitive technique, the Single Molecule Array (Simoa). Multivariable linear regression was conducted to examine the associations between circulating IL-2 levels and clinical as well as cardiovascular manifestations of SLE. In multivariable analyses, serum IL-2 levels showed significant positive associations with inflammatory markers including C reactive protein and IL-6. Disease activity, assessed by SLEDAI-2K, was positively correlated with IL-2 levels. Positive and significant associations were also noted, after adjustment for covariates, between IL-2 and specific autoantibodies, including anti-DNA, anti-Sjögren's syndrome antigen A (SSA), anti-Sjögren's syndrome antigen B (SSB), anti-Smith (Sm) and antiribosome. Regarding cardiovascular disease factors, triglycerides were positively associated with IL-2 whereas high-density lipoprotein-cholesterol exhibited an inverse relationship. Significant correlations exist between serum IL-2 levels and markers of inflammation, lipid profile, disease activity and specific autoantibody profiles in patients with SLE. These findings underscore the pivotal role of IL-2 in SLE immunopathogenesis, reflecting its intricate involvement in modulating both inflammatory responses and metabolic pathways.

Anifrolumab (ANI), a type I interferon receptor antagonist, has demonstrated clinical efficacy in systemic lupus erythematosus (SLE). However, its effects on serological markers commonly used to assess disease activity in clinical practice remain uncertain. This study evaluated changes in complement and autoantibody levels in SLE patients treated with ANI under routine care conditions. We performed a single-center retrospective analysis of SLE patients receiving ≥3 ANI infusions over a 12-month period. Clinical and serological data, including complement (C3c, C4), anti-double-stranded DNA (anti-dsDNA) antibodies, prednisone dose, and SLE Disease Activity Index 2000 (SLEDAI-2K) scores, were analyzed using mixed-effects modeling (REML). Correlations between changes in clinical SLEDAI-2K (excluding serological components) and serological markers were assessed. Thirteen patients (84.6% female, median age 53 years) were included. The median baseline SLEDAI-2K was 10, and 76.9% exhibited abnormal complement and/or anti-dsDNA levels. Over the treatment course (median 12 infusions), 76.9% of patients improved clinically, with a mean SLEDAI-2K reduction of 3.77 ± 2.78 points (p < 0.001). Prednisone doses decreased in 38.5% of cases. Complement (C3c, p = 0.25; C4, p = 0.10) and anti-dsDNA levels (p = 0.12) remained largely unchanged. No correlations were observed between clinical SLEDAI-2K improvement and serological parameters. Anifrolumab therapy led to significant clinical improvement without corresponding serological changes, suggesting that traditional biomarkers may not adequately reflect therapeutic response. Monitoring under ANI should therefore emphasize clinical rather than serological parameters. These findings have implications for interpreting composite disease activity indices incorporating immunological markers in SLE management depending on the mechanism of action of a particular treatment.

This study aimed to compare the performance of the Lupus Foundation of America Rapid Evaluation of Activity in Lupus (LFA-REAL), British Isles Lupus Assessment Group Index (BILAG), and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) in detecting the clinician's perception of improvement and worsening disease and identifying patients requiring treatment escalation. This was a prospective, observational study conducted at four centers. Adults with systemic lupus erythematosus were evaluated at a baseline and follow-up visit. Disease activity was assessed using SLEDAI, BILAG, and LFA-REAL at both visits by the same physician. At the follow-up visit, the Clinician Global Impression of Change (CGIC) was recorded to classify patients as improved, worsened, or unchanged. Receiver operating characteristic curve analysis was used to evaluate each instrument in detecting clinician-rated change gauged by CGIC with optimal cut-off points determined using the Youden Index. Of the 163 patients enrolled, 145 (89%) completed a follow-up visit. Based on CGIC, 23% improved, 16% worsened, and 61% remained stable. For detecting CGIC-defined improvement, LFA-REAL had an area under the curve (AUC) of 0.85 (95% confidence interval [CI] 0.77-0.92), compared to 0.75 (95% CI 0.66-0.85) for BILAG and 0.74 (95% CI 0.64-0.84) for SLEDAI. For CGIC-defined worsening, AUCs were 0.86 (95% CI 0.77-0.96), 0.79 (95% CI 0.67-0.90), and 0.76 (95% CI 0.66-0.87). Of those with CGIC-defined worsening, eight (35%) required treatment escalation. LFA-REAL identified a difference of ≥10 mm in all eight of these patients, compared to four by BILAG and two by SLEDAI. LFA-REAL showed comparable performance relative to SLEDAI and BILAG in detecting clinician-rated change. There was a statistically significant advantage over SLEDAI for detection of improvement. These findings support its utility as a metric for disease activity in clinical practice and research.

Despite the reported clinical significance of anti-C1q immunoglobulin G autoantibodies (anti-C1q) for SLE and the development of anti-C1q commercial kits, their performance characteristics in routine patient evaluation remain poorly defined. In this cross-sectional study, an unselected cohort of 107 patients with suspicion of a systemic autoimmune disease and 102 controls were included and evaluated for anti-C1q autoantibodies with three kits (Bühlmann, Orgentec and Werfen). Patients in the unselected cohort were classified as having SLE or a mimicker condition. Disease activity was assessed using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2K and SLE patients were subclassified based on the presence of lupus nephritis (LN) (history/active). Each kit was assessed for diagnostic performance. The degree of association between anti-C1q and SLEDAI/complement levels was assessed using the Spearman correlation coefficient (rho). Between-kit agreement was evaluated using Fleiss Ƙ. Werfen had the best performance in discriminating patients with SLE from non-SLE (area under the curve (AUC)=0.76), whereas for the SLE versus mimicker comparison Bühlmann (AUC=0.71) and Werfen (AUC=0.71) exhibited adequate discrimination. Among patients with SLE, all kits exhibited poor discrimination of patients with history of LN versus non-renal SLE, but Orgentec displayed good discrimination for patients with active LN from non-active LN (AUC=0.74). A positive correlation was observed between anti-C1q and SLEDAI scores, whereas a negative correlation was found between anti-C1q and complement C3 and C4 across all kits. Agreement for SLE between the three kits was moderate (Ƙ=0.42). Anti-C1q can identify patients with SLE and correlate with global and renal disease activity, highlighting their potential to function as follow-up markers in SLE. Agreement with commercial anti-C1q kits is variable. Further studies are required to harmonise anti-C1q kits for optimal routine patient evaluation.