Lupus Science & Medicine最新文献

Objective: Pregnant patients with systemic lupus erythematosus (SLE) have 2-3 times higher risk of preterm delivery (PTD). Hydroxychloroquine (HCQ) is recommended during pregnancy and may reduce PTD risk. This study investigates whether early pregnancy HCQ-use reduces PTD risk in a diverse SLE cohort.

Methods: We included singleton pregnancies reaching ≥20 weeks' gestation (2011-2020) among patients with SLE aged 18-50 receiving care at Kaiser Permanente Northern California. HCQ exposure was defined as ≥2 prescriptions filled from 3 months before the last menstrual period through the first trimester. PTD was defined as delivery <37 weeks and continuously as gestational weeks for time-to-delivery analyses. Propensity scores (PS) based on demographics, comorbidities and medication use were calculated to address confounding. Risk ratios (RR) and HRs, including 95% CIs, were estimated using PS-adjusted Poisson regression with robust SEs and Cox regression, stratified by parity. To investigate effect modification, we stratified by prepregnancy comorbidities and pregnancy corticosteroid use.

Results: Among 399 pregnancies in 324 patients, 21% were preterm. The PS-adjusted RR was 1.08 (95% CI 0.52 to 2.23) and 0.88 (95% CI 0.50 to 1.57) for nulliparous and multiparous pregnancies exposed to HCQ, respectively. The PS-adjusted HRs were similar, and results remained consistent across analyses stratified by potential effect modifiers.

Conclusions: Although periconceptional HCQ-use was not associated with reduced PTD nor appreciably altered gestational age at delivery, we found no increased risks for these specific adverse outcomes. Consistent with other work, we found potentially protective associations in subsets stratified by parity. However, we had limited statistical power to test this.

Objectives: SLE associated with immune checkpoint inhibitors (ICIs) is rare, and a comprehensive profile of ICI-induced SLE remains poorly characterised. This study aimed to explore the potential association between ICIs and SLE and characterise clinical features.

Methods: We extracted adverse event reports of patients with cancer with SLE from the FAERS (US Food and Drug Administration Adverse Event Reporting System) database (Q1 2011-Q4 2024). A disproportionality analysis was conducted using the reporting OR (ROR) and the information component, with adjusted ROR calculated via logistic regression to control for confounders.

Results: 146 066 ICI-related adverse events cases from patients with cancer were identified. Among these, 209 (median (IQR) age 63 (55.3-71.7) years; 106 (51%) female) cases of SLEs were reported. Our analysis detected significant positive signals for SLE associated with ICIs overall, particularly for anti-programmed cell death protein 1 (PD-1) and anti-programmed death-ligand 1 therapy. Eight positive signals of SLEs were identified, predominantly cutaneous lupus and SLE. The risk of ICI-related SLEs was significantly higher in females than in males. However, age and chemotherapy were not significant risk factors for the incidence of ICI-related SLEs. The risk was higher with anti-PD-1 therapy compared with other ICI therapies. Patients with lung cancer, melanoma or breast cancer appeared to be at higher risk. Most patients experienced serious outcomes, with a mortality rate of 4.31% (nine cases).

Conclusion: This first pharmacovigilance study identified a significant association between ICI use and SLEs, suggesting ICIs may constitute a novel class of drug-induced SLE triggers. Personalised long-term safety monitoring for ICIs is warranted for high-risk patients (eg, females, anti-PD-1 recipients).

Background: SLE complicated with thrombotic thrombocytopenic purpura (SLE-TTP) is a rare but potentially fatal condition. Current studies regarding SLE-TTP are limited to case reports and literature reviews. This study presents a cohort of patients with SLE-TTP and aims to investigate their clinical characteristics and treatment outcomes, as well as to explore the efficacy of rituximab (RTX) maintenance therapy (RMT) for relapse prevention and long-term disease control.

Methods: Patients with SLE-TTP were retrospectively identified in an SLE cohort. Baseline characteristics, acute-phase treatment responses and long-term outcomes were collected. All patients received RTX-containing induction therapy during the acute phase of TTP. Maintenance therapy was categorised as RMT (regular RTX infusions) or non-RMT (conventional immunosuppressants and/or biologics) regimens. TTP relapse, lupus low disease activity state (LLDAS) and infection rates were compared between groups.

Results: Of 33 patients with SLE-TTP, 31 (94%) achieved clinical remission following RTX-containing induction therapy, while 2 died during the acute phase. Fourteen patients (45%) received RMT, and 17 (55%) received non-RMT regimens. During a median follow-up of 22.9 months, TTP relapse occurred in seven (23%) patients: one (7%) in the RMT group and six (35%) in the non-RMT group. Kaplan-Meier analysis revealed significantly longer relapse-free survival with RMT (log-rank p=0.027). All patients receiving RMT achieved LLDAS, compared with 59% of patients in the non-RMT group. Infection rates were comparable between the two groups.

Conclusions: RTX-containing induction regimens resulted in high rates of clinical remission in patients with SLE-TTP. RMT was associated with a significantly reduced risk of TTP relapse and superior long-term control of SLE disease activity, without an excess risk of severe infection. These findings support RMT as a potential option for long-term management of SLE-TTP.

Objective: Breastfeeding prevalence and challenges among women of systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) is under-researched especially in the Middle East-North Africa region. This study aimed to assess breastfeeding initiation, duration and predictors of early discontinuation (<6 months post partum) among Egyptian mothers with SLE or RA.

Methods: This multicentre retrospective cohort study included 320 pregnancies: 62 SLE (105 pregnancies), 71 RA (110 pregnancies) and 59 healthy mothers (105 pregnancies). Data on pregnancy history, breastfeeding intent, initiation, duration and weaning reasons were collected.

Results: Exclusive breastfeeding was lowest in SLE (29.9%) vs RA (50.6%) and controls (60%, p<0.001). Continuation beyond 6 months was significantly lower in SLE (36.2%) and RA (33.6%) vs controls (81%, p<0.001). Postpartum depression independently predicted discontinuation in SLE (adjusted OR (aOR)=0.06, 95% CI 0.01 to 0.6) and RA (aOR=0.34, 95% CI 0.13 to 0.9). Multivariable generalised estimating equation confirmed SLE reduced breastfeeding odds versus controls (aOR=0.41, p=0.040).

Conclusion: Breastfeeding is significantly less prevalent among Egyptian mothers with SLE and RA when compared with control group. Targeted educational programme and support may help improve breastfeeding rates in SLE/RA mothers.

Objective: SLE is a complex, heterogenous autoimmune disease. SLE researchers do not always collect the same data, making comparative studies difficult. We aimed to ascertain what variables SLE clinical researchers commonly collect for SLE research. Our ultimate goal is to generate a minimal core dataset for future SLE studies.

Methods: In 2020, we designed and distributed a questionnaire to members of the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) as well as additional active research centres in China. Our survey included 26 questions about the types of data that are routinely collected for research. Variables collected by ≥75% of participating respondents were used as a threshold for inclusion.

Results: 18 of 36 invited respondents replied (8 from USA/Canada, 5 from China and 5 from Europe). Many key variables in the domains of sociodemographics, SLE specific, comorbidities, baseline haematology/biochemistry/immunology and treatment data were collected by ≥75% respondents including the 1997 American College of Rheumatology (ACR) Classification Criteria (83%), SLE Disease Activity Index-2000 (82%), current treatment (100%), drug name, dose, frequency and start date (75-100%) and complement C3/4 (94%). A range of other items was collected by 50-<75% of respondents including SLICC 2012 Criteria (67%), SLICC/ACR Damage Index (68%) and Short Form Health Survey-36 (53%). Less than 50% of respondents collect certain items including European Alliance of Associations for Rheumatology/ACR 2019 criteria (33%), British Isles Lupus Assessment Group scores (12%) and pneumococcal vaccine status (39%).

Conclusions: The frequency with which an initial set of variables is collected in SLE cohorts globally was identified and can form the basis from which to develop a core minimum dataset for SLE. Further refinement and common definitions will be needed to finalise a minimal core dataset suitable for widespread use.

Objective: Youth with childhood-onset SLE (cSLE) have increased risk of serious infection. It is unknown how much of this risk is due to modifiable factors such as choice of immunosuppressant. We aimed to compare hospitalised infection rates in youth with cSLE on different disease-modifying antirheumatic drugs (DMARDs).

Methods: We included youth ≤18 years with cSLE treated from 2009 to 2022 at two centres. Clinical data were extracted from electronic health records and the Paediatric Health Information System. Hospitalised infection frequency was calculated over the first year of treatment in youth included in each DMARD exposure group, stratified by lupus nephritis (LN) status. Cox proportional hazard regression with inverse probability of treatment weighting (IPTW) was used to compare infection rates across DMARD groups, adjusting for corticosteroid dose.

Results: Among 257 youths with cSLE, 5% had ≥1 hospitalised infection within 1 year of DMARD initiation. 8% of those with LN had ≥1 hospitalised infection compared with 2.5% without LN. In IPTW-adjusted models, children with LN treated with mycophenolate had lower risk of infection compared with those treated with cyclophosphamide (HR 0.12; 95% CI 0.019 to 0.88). Among those without LN, mycophenolate did not differ from azathioprine in infection risk (HR 1.67, 95% CI 0.56 to 4.99). Higher oral corticosteroid dosing (per 1 mg/day of prednisone) was associated with increased risk of infection (HR 1.1, 95% CI 1.05 to 1.15).

Conclusions: We observed higher hospitalised infection rates in children with cSLE and LN compared with those without LN. Among children with LN, those who received cyclophosphamide had more infections than those who received mycophenolate. Methotrexate was associated with lower infection rates than mycophenolate or azathioprine among youth without LN. Higher daily oral steroid dose was significantly associated with increased hospitalised infection risk in youth with non-renal SLE.

Background: Neuropsychiatric SLE (NPSLE) is a clinically challenging subset of SLE, marked by heterogeneous central nervous system involvement. Diagnosis relies on clinical symptoms and exclusionary criteria, lacking objective biomarker.

Purpose: To investigate metabolic patterns of intracerebral lesions and identify diagnostic biomarkers for NPSLE using translocator protein (TSPO) positron emission tomography (PET)/magnetic resonance (MR).

Methods: A retrospective analysis was conducted on 19 patients with NPSLE and 10 patients with non-NPSLE, who underwent [¹⁸F] DPA-714 PET/MRI. Diagnoses of SLE and NPSLE followed American College of Rheumatology (ACR) classification and Systemic Lupus International Collaborating Clinics (SLICC) Model B criteria. T2-weighted MRI lesions served as regions of interest (ROI), coregistered to PET for cross-modality quantitative analysis. The maximum uptake (SUVmax) and mean uptake (SUVmean) of brain lesions for each patient was measured. Group differences in SUVmax and SUVmean were compared. Clinical associations were conducted using Pearson correlation, and differentiation between non-NPSLE and NPSLE was performed by logistic regression analysis.

Results: SUVmax was significantly higher in the NPSLE group than in the non-NPSLE group (p<0.01), while there was no significant difference in SUVmean (p>0.05). SUVmax was correlated with clinical assessment scores (SLICC/ACR: r=0.43, p=0.02; modified Rankin Scale: r=0.41, p=0.04; SLE Disease Activity Index: r=0.41, p=0.03), and no significant correlation was found for SUVmean. In logistic regression analysis, only the model based on SUVmax alone was significant (p=0.01). In ROC analysis, the area under the curve (AUC) of SUVmax (0.83) was higher than that of SUVmean (0.68), and Model 4 (SUVmax+SUVmean + Interaction) showed the best diagnostic performance (AUC=0.94).

Conclusions: Patients with NPSLE and non-NPSLE showed distinct TSPO uptake in brain lesions, indicating different pathophysiology. TSPO PET/MR may serve as a potential imaging biomarker for differentiating NPSLE, providing insights for clinical diagnosis and mechanistic stratification in SLE.

Objective: To determine vitamin D receptor (VDR) blood serum concentrations in patients with SLE and to assess the relationship with vitamin D status, disease course, bone turnover markers levels and bone mineral density (BMD).

Methods: The cross-sectional study involved 99 patients with SLE and 30 controls. We assessed VDR, vitamin D, C-reactive protein (CRP), interleukin (IL) 6, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX) concentrations, and erythrocyte sedimentation rate (ESR) in study subjects. Dual-energy X-ray absorptiometry was also performed.

Results: Mean VDR levels in patients with SLE and in the control group were 12.78±0.61 ng/mL and 23.12±0.61 ng/mL, accordingly (p<0.01). 77.8% patients with SLE had low VDR concentrations and only 22.2% patients presented relatively normal or high levels. Low VDR levels in patients with SLE were associated with age (p=0.054, r=-0.22). The study did not reveal a relationship between VDR level and sex, disease duration, body mass index (BMI) and cumulative glucocorticoid (GC) dose. No association was found between VDR level and a diagnosed lupus nephritis, creatinine concentration and glomerular filtration rate. The correlation analysis confirmed the association of low VDR level with high disease activity, namely with elevated CRP (r=-0.22), IL-6 (r=-0.21) levels, SLE Disease Activity Index 2000 variant (r=-0.20). VDR concentration was closely associated with vitamin D supply. The average level of vitamin D in patients with low VDR was 33.55% lower than in the group with a relatively normal vitamin concentration (p=0.0001, r=0.47). We revealed a proportional increase of CTX concentration associated with VDR decrease (p<0.05, r=-0.27). No significant difference in average Z-score, T-score and BMD between the groups of patients with SLE with low and relatively normal VDR levels (p>0.05) was found.

Conclusion: Low VDR concentration is a common phenomenon in patients with SLE associated with age, high disease activity, vitamin D supply and serum CTX concentration. VDR concentration had no significant association with sex, disease duration, cumulative GC dose, BMI, a diagnosed lupus nephritis, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, OC level and BMD.

Objectives: The central nervous system is a significant extraglandular target in primary Sjögren's syndrome (pSS), often characterised by cognitive deficits. However, the underlying mechanisms remain elusive. This study aims to investigate the alterations in amplitude of low-frequency fluctuations (ALFF) in patients with pSS and to explore whether it exhibits frequency dependence and temporal variability, attempting to explore its mechanism.

Methods: The study comprised 68 patients with pSS and 69 healthy controls, all of whom underwent resting-state functional MRI and neuropsychological assessments. The ALFF method was used to ascertain whether frequency-dependent alterations occur within the slow-5 (0.01-0.027 Hz) and slow-4 (0.027-0.073 Hz) frequency bands. Additionally, dynamic ALFF (dALFF) analysis was conducted to explore the temporal variability. Ultimately, the correlation between the abnormal brain regions and neuropsychological assessments was elucidated.

Results: The right fusiform gyrus of patients with pSS shows abnormalities in ALFF and its two sub-bands, while the left precentral gyrus and right middle frontal gyrus exhibited abnormal increase limited to the slow-5 frequency band. dALFF showed an abnormal activity in the left supplementary motor area in patients with pSS. Additionally, the differential brain regions identified by the slow-5 frequency band of ALFF correlated with certain neuropsychological scales.

Conclusions: This research indicates that ALFF metrics offer enhanced insights into the alterations of regional brain function in patients with pSS, which exhibits both frequency-dependent and temporal variability characteristics, complementing traditional metrics and enhancing our comprehension of brain function in pSS and suggests that ALFF may emerge as a novel instrument for exploring the underlying neural mechanisms in patients with pSS.

Background: The purpose of this study was to reveal the morphological changes of grey matter (GM) in women systemic lupus erythematosus (wSLE) patients with mild cognitive impairment (MCI) with normal conventional MRI.

Methods: The differences in brain morphological indicators among wSLE with MCI, wSLE without MCI and women healthy control (wHC) group were calculated and compared by voxel-based morphometry and surface-based morphometry. The GM volume (GMV), cortical thickness (CT), indicators of cortical complexity, including fractal dimension (FD), gyration index (GI), sulcus depth, the relationship between brain morphological indicators and clinical features, were analysed.

Results: In comparison to wSLE patients without MCI (n=36), wSLE with MCI (n=26) demonstrated a significant decrease in FD of the left lateral orbitofrontal gyrus. When compared with the wHC group (n=36), both wSLE patients with MCI and wSLE without MCI group exhibited a reduction in GMV in the medial of right superior frontal gyrus, a thinning of CT in the left paracentral and postcentral gyrus as well as in the right pars triangularis gyrus and superior frontal gyrus. Within the wSLE group, Mini-Mental State Examination scores were positively correlated with GMV in the middle of right superior frontal gyrus and with the FD of the left lateral orbitofrontal gyrus.

Conclusion: WSLE patients with MCI have brain morphological changes such as reduced GMV, thinning CT, reduced FD and increased GI. Cortical morphological changes may be involved in the pathological process of MCI in wSLE patients.