Objectives Pregnancy in SLE is associated with increased maternal and fetal risks but its impact on irreversible organ damage remains unclear. We assessed whether pregnancy independently contributes to short-term organ damage accrual in women with SLE.Methods We retrospectively analysed prospectively collected data from two tertiary referral centres with dedicated pregnancy clinics. Women fulfilling SLE classification criteria were included if complete damage assessments were available from 2 years before conception to 1 year after conception. Organ damage was assessed using the Systemic Lupus International Collaborating Clinics Damage Index (SDI). Within-patient SDI changes during the pregnancy/early postpartum period were compared with the pre-pregnancy reference period. Given the limited number of events, effect sizes and CIs were prioritised. Sensitivity analyses included non-parametric effect sizes and restriction to one pregnancy per woman.Results 165 pregnancies were included. At conception, most women were in remission or low disease activity. During pregnancy, 20.6% experienced disease flares, predominantly mild to moderate. Overall, cumulative damage remained stable: mean SDI increased from 0.18±0.43 one year before conception to 0.22±0.52 one year after conception (mean ΔSDI 0.04±0.21), with a median change of zero. Only seven pregnancies (4.2%; 95% CI 2.1% to 8.5%) showed new damage, limited to a single SDI item. Pre-existing damage was associated with progression (OR 6.77; 95% CI 1.43 to 32.05), and the frequency of progression was similar when the analyses were restricted to a single pregnancy per woman (6/126, 4.8%). By contrast, disease activity at the time of conception, flare-ups, obstetric complications and treatments were inconclusive. In the sensitivity analysis, the association with pre-existing damage was confirmed, and baseline disease activity also emerged as associated with damage progression (rank-biserial r=−0.55; 95% CI −0.78 to −0.27, p=0.030).Conclusions In women with predominantly well-controlled SLE, short-term organ damage accrual during pregnancy and the early postpartum period was uncommon. Pre-existing damage was associated with further accrual, while baseline disease activity also emerged as associated in the sensitivity analysis; however, the small number of events limits conclusions regarding other potential risk factors.
Objective The Systemic Immune-Inflammation Index (SII) is an accessible haematological marker reflecting systemic inflammatory burden. In SLE, type I interferon-associated chemokines have been proposed as biomarkers of disease activity. This study evaluated the discriminatory performance of the SII between patients with SLE and healthy individuals and its correlation with disease activity and circulating interferon-associated chemokines.Methods In this cross-sectional study, we analysed data from 95 women with SLE and 1443 healthy female controls from two established cohorts. The SII was calculated as (neutrophil count × platelet count) / lymphocyte count. Disease activity was assessed using the SLE Disease Activity Index 2000 (SLEDAI-2K). Serum levels of CCL11/eotaxin-1, CCL2/MCP-1, CCL5/RANTES, CCL3/MIP-1α, CCL4/MIP-1β, CXCL10/IP-10, CXCL12/SDF-1α, CXCL1/GRO-α and CXCL8/IL-8 were quantified using a multiplex assay.Results Median SII values were significantly higher in patients with SLE than in healthy controls (588.8 (IQR 390.8–964.8) vs 521.4 (IQR 381.6–690.5); p=0.022), though its discriminatory performance was limited (area under the curve (AUC)=0.57; 95% CI 0.49 to 0.64; p=0.022). Within the SLE cohort, the SII correlated positively with SLEDAI-2K scores (Spearman’s ρ=0.303; 95% CI 0.102 to 0.480; p=0.003), but showed no significant correlations with any circulating chemokines. Conversely, SLEDAI-2K scores initially demonstrated nominal positive correlations with serum CCL5/RANTES (ρ=0.257; 95% CI 0.008 to 0.475; unadjusted p=0.037) and CXCL8 (ρ=0.228; 95% CI 0.012 to 0.422; unadjusted p=0.032); however, no chemokine maintained statistical significance after false discovery rate multiple-testing correction.Conclusion Although the SII correlates with overall SLE disease activity, it does not reflect circulating concentrations of interferon-associated chemokines.
Objective Investigate the effect of anifrolumab on fatigue in patients with SLE and low disease activity and identify cellular mechanisms associated with the fatigue response.Methods 12 SLE patients with significant fatigue (Fatigue Assessment Scale (FAS)1 ≥22) initiating anifrolumab were followed at baseline, 1 month and 3 months. The primary endpoint was fatigue improvement (FAS reduction ≥4 points). Secondary endpoints included FAS, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), Generalised Anxiety Disorder-7, Quick Inventory of Depressive Symptomatology Self-Report-16, serum interferon (IFN)-α, type I IFN activity and γH2AX expression in myeloid subsets by flow cytometry.Results Median baseline SLEDAI was 4 (IQR 4–7) and median FAS was 28 (IQR 24–36). Fatigue improvement, defined by FAS reduction ≥4 points, was observed in 58% of patients (7/12; 95% CI 29% to 88%) at 3 months. Serum IFN-α was low across the cohort and did not predict response. Baseline γH2AX in plasmacytoid dendritic cells (pDCs) was significantly higher in responders than in non-responders and healthy controls and showed a declining trend after 1 month of treatment (Wilcoxon signed-rank test, n=6, p=0.156).Conclusions These preliminary findings suggest that anifrolumab may improve fatigue in patients with SLE including those with low disease activity and low serum IFN-α. Elevated pDC γH2AX at baseline, reflecting subclinical cellular stress, may identify patients who could benefit from IFN blockade for fatigue. These hypothesis-generating findings warrant validation in controlled studies.
Background SLE is a complex autoimmune condition requiring evaluation across disease activity, permanent damage and health-related quality of life (HRQoL). This study aimed to validate the Bengali version of the 34-item Lupus Quality of Life (Lupus-QoL) and perform a correlation analysis with global disease activity (SLE Disease Activity Index 2000 (SLEDAI-2K), SLE Disease Activity Score (SLE-DAS)), organ-specific involvement (British Isles Lupus Assessment Group (BILAG)), permanent damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (SDI)) and clinical targets like the Low Lupus Disease Activity State (LLDAS).Method A multicentre cohort study was conducted with 240 Bengali patients with SLE. Clinical status was concurrently assessed using physician-reported indices (SLEDAI-2K, SLE-DAS, BILAG, SDI) alongside the Bengali Lupus-QoL. Internal consistency was determined by Cronbach’s alpha while associations were evaluated using Spearman’s correlation and discriminant validity via independent t-tests.Result The tool demonstrated excellent internal consistency (Cronbach’s alpha 0.86–0.97). SLEDAI-2K showed a strong negative correlation with all quality-of-life domains (p<0.01). While SLE-DAS correlated with physical and functional domains, it failed to capture fatigue, body image or intimacy. Musculoskeletal and cardiorespiratory involvements were the primary drivers of reduced HRQoL. Achieving LLDAS significantly improved physical health and planning (p=0.03) but not psychosocial domains. Permanent damage (SDI ≥1) significantly restricted physical capabilities and functional planning (p<0.01).Conclusion The Bengali Lupus-QoL is a highly reliable instrument that bridges the gap between medical data and patient experience. Standard clinical metrics like SLE-DAS and LLDAS are insufficient to capture the full psychosocial burden, highlighting the necessity of this tool for the comprehensive management of Bengali patients with SLE.
Objective Systemic lupus erythematosus (SLE) is associated with increased risk for adverse pregnancy outcomes (APOs). The Predictors of Pregnancy Outcomes: Biomarkers in Antiphospholipid Syndrome and SLE (PROMISSE) study set the benchmark for APO rates in SLE but used narrow APO definitions, including only outcomes deemed most severe, and excluded high-risk patients. Therefore, PROMISSE may underestimate the true burden of APOs in SLE and how PROMISSE findings translate to real-world SLE pregnancies is unclear.Thus, we sought to evaluate APO rates and predictors, including Definition of Remission in SLE (DORIS) status, influenced by inclusion criteria and APO definitions.Methods We studied 107 SLE pregnancies in 107 individuals from a prospective cohort, with multifetal pregnancies as the sole exclusion criterion. The cohort was analysed overall and in two subgroups, a PROMISSE-eligible subset meeting PROMISSE inclusion criteria (n=90) and a higher-risk PROMISSE-ineligible (based on proteinuria >1 g/g, hypertension, prednisone >20 mg/day, serum creatinine >1.2 mg/dL and/or diabetes) subset (n=17). APOs were defined using PROMISSE and selected American College of Obstetricians and Gynecologists (ACOG) definitions.Results Using PROMISSE-defined outcomes, APOs occurred in 30% of the total cohort, 24% of the PROMISSE-eligible subset and 59% of the higher-risk PROMISSE-ineligible subset. Applying ACOG definitions increased event rates across all groups (50%, 43% and 82%, respectively). APOs, particularly preterm birth and pre-eclampsia, were observed more frequently among patients not in DORIS remission. All three neonatal deaths and all three pregnancy losses occurred in patients in non-remission.Conclusions APO rates in SLE are highly impacted by the patient population studied and outcome definitions. Across disease severity, APOs were observed more frequently in the absence of DORIS remission. The high APO rate in the PROMISSE-ineligible subset reflects patients with high-risk clinical features for whom pregnancy would often be deferred until disease optimisation, emphasising the need for robust preconception counselling in SLE patients.
