BackgroundAntiphospholipid syndrome (APS) is an autoimmune condition marked by thrombosis and pregnancy complications caused by antiphospholipid antibodies (aPL). This study evaluates immunological, inflammatory, and endothelial biomarkers in primary and secondary APS and SLE to determine their association with clinical outcomes.Material and methodsWe conducted a cross-sectional study including patients with primary (PAPS) (n = 79), secondary (SAPS) (n = 47), SLE (n = 36), and control group (n = 56). Serum and plasma samples were analyzed for aPLs, inflammatory markers (hs-CRP, IL-6), endothelial markers (endoglin), platelet activation (CD41/CD61), tissue factor, and iron metabolism markers (hepcidin, ferritin, UIBC) using ELISA and automated assays. Statistical analyses included group comparisons, correlations, multivariate logistic regression analysis and principal component analysis (PCA).ResultsNon-criteria aPLs, were significantly elevated in all patient groups compared to controls (p < 0.001). Patients with SAPS demonstrated significantly higher levels of aCL IgG, aCL IgA, aβ2GPI IgM, and aPS/PT (IgG and IgM) compared to PAPS. Strong correlations were identified between aPS/PT IgG and the lupus anticoagulant ratio (LAR) (r = 0.670, p < 0.001), as well as between aβ2GPI IgG and LAR (r = 0.625, p < 0.001). Multivariate logistic regression identified that endoglin and ferritin were independently associated with clinical manifestations. For fetal loss, the model was statistically significant (χ[21] = 16.18, p = 0.013); an increase in endoglin raised the probability by 45.1% (OR = 1.451, p = 0.040), while lower ferritin levels were also independently associated (p = 0.004). Ferritin showed the strongest independent association with thrombosis (χ[21] = 19.87, p = 0.011), with each unit increase raising the probability of a thrombotic event by 1.5% (OR = 1.015). PCA identified two main factors explaining 63% of the variance: an "Immunological-related" factor (42.96%) dominated by aCL IgG, aβ2GPI IgG, aPS/PT IgG, and aCL IgA, and a "Prothrombotic and metabolic-related" factor (20.06%) driven by aβ2GPI IgM, tissue factor, aCL IgA, and inversely by UIBC.ConclusionThe study highlights the interplay of immune, inflammatory, and endothelial dysfunction biomarkers in APS and their association with clinical manifestations. Combined assessment of conventional and non-criteria biomarkers may improve understanding of disease mechanisms and support a more comprehensive evaluation of patients with APS.

ObjectiveTo characterize the burden and MRI subtypes of cerebral small vessel disease (cSVD) in antiphospholipid syndrome (APS) and to identify clinical factors associated with cSVD.MethodsWe retrospectively analyzed 132 patients with APS and age- and sex-matched healthy controls. MRI markers for cSVD, including lacunes, enlarged perivascular spaces (EPVS), microbleeds, and white matter hyperintensities (WMH), were rated using validated scales. Total cSVD scores (0-4) were calculated. Logistic regression analyses adjusted for age, sex, and disease duration were used to identify risk factors.ResultsMore than half of patients with APS (51.5%) exhibited cSVD, whereas only 24.2% had a history of stroke. Lacunes were the predominant subtype (46.2%), followed by WMH (16.7%), EPVS (14.4%), and microbleeds (12.1%). Subclinical cSVD was present in 34.8% of patients with APS without neurological symptoms. Hypertension (OR 3.69, 95%CI 1.17-11.65, p = 0.026), prior thrombosis (OR 22.15, 95%CI 2.11-232.27, p = 0.010), and prior stroke (OR 10.71, 95%CI 2.47-46.36, p = 0.002) were independently associated with cSVD, while individual aPL profiles were not.ConclusioncSVD is a common feature in patients with APS and often occurs in the absence of neurological manifestations. The predominance of lacunes suggests a pattern of recurrent microvascular injury. Hypertension and thrombotic history are major contributors, underscoring the need for comprehensive vascular risk assessment. These findings highlight the potential value of MRI screening in selected patients with APS and call for longitudinal studies to clarify its prognostic significance.

ObjectivesGalectin-9 and IP-10 are downstream effectors of the type I interferon (IFN) pathway and have been proposed as surrogate biomarkers of IFN signature in systemic lupus erythematosus (SLE). This study aimed to investigate the association of serum Galectin-9 and IP-10 levels with disease activity in lupus nephritis (LN) and to compare them with those in disease controls, including antiphospholipid syndrome (APS) and primary Sjögren's disease (pSD), and healthy controls.MethodsFifty-nine patients with biopsy-proven LN (31 active, 28 inactive), 36 patients with APS, 17 patients with pSD, and 61 healthy volunteers were enrolled. All SLE patients fulfilled both the SLICC and the 2019 EULAR/ACR classification criteria. Serum Galectin-9 and IP-10 levels were measured by enzyme-linked immunosorbent assay (ELISA) in samples obtained at the same visit as the disease activity assessment. In patients with active LN, kidney biopsy was performed as part of the same clinical evaluation, whereas patients with inactive LN had a previously established biopsy-proven diagnosis of LN.ResultsAmong 59 LN patients (74.6% female; mean age 37.9 ± 12 years), serum levels of both biomarkers were significantly higher in the active LN group compared with inactive LN, APS, pSD, and healthy controls (p ≤ 0.05). Biomarker levels did not differ significantly among the inactive LN, APS, and pSD groups (p > 0.05); however, all three groups showed significantly higher levels compared to healthy controls (p ≤ 0.05). Both biomarkers showed weak but statistically significant correlations with SLEDAI scores (Galectin-9: r = 0.36, p = 0.004; IP-10: r = 0.33, p = 0.009). ROC analysis demonstrated moderate discriminatory ability for distinguishing active from inactive LN (AUC: 0.695 for Galectin-9; 0.658 for IP-10).ConclusionSerum Galectin-9 and IP-10 are elevated in active LN and show weak but statistically significant correlations with SLEDAI scores. However, elevated levels are not specific to LN, as similar values are observed in inactive LN, APS, and pSD, suggesting these markers reflect a shared IFN-driven inflammatory state rather than LN-specific pathology.

ObjectiveTo characterize the burden of herpes zoster (HZ) in systemic lupus erythematosus (SLE) and to examine clinical correlates of HZ and patients' attitudes toward the recombinant zoster vaccine (RZV).MethodsWe conducted a single-center retrospective cohort study combined with a cross-sectional survey among consecutive adult outpatients with SLE between December 2024 and June 2025. HZ episodes after SLE diagnosis were ascertained via structured interviews. Incidence rates were calculated as the number of HZ episodes per 1000 person-years from SLE diagnosis to enrollment. Participants were classified into three groups according to the number of HZ episodes: HZ[0], HZ[1], and HZ[≥2] groups. Factors associated with HZ development were assessed using multivariable logistic regression. Patients were asked about willingness to receive RZV ("yes", "no", or "not sure") and reasons for the response.ResultsAmong 170 patients with SLE, 73 (43%) reported at least one HZ episode after SLE diagnosis, and 29 (40% of those with HZ) reported recurrent HZ. During 3138 person-years of follow-up, at least 102 HZ episodes were reported, yielding a minimum incidence of 32.5 per 1000 person-years. In multivariable analysis, ever use of azathioprine (OR 2.74, 95% CI 1.03-7.29) and renal dysfunction (OR 2.59, 95% CI 1.04-6.48) were associated with HZ development. Attitude data were available for 159 patients: 31 (20%) were willing to receive RZV, 47 (30%) were unwilling, and 81 (50%) were unsure.ConclusionsHZ was common and frequently recurrent in this Japanese SLE cohort. Ever use of azathioprine and renal dysfunction were associated with HZ development, while willingness to receive RZV was low. Risk-stratified clinician counselling and shared decision-making may improve acceptance of HZ prevention strategies in high-risk patients with SLE.

BackgroundThe prognostic relevance of lupus nephritis (LN) occurring at systemic lupus erythematosus (SLE) onset versus later remains uncertain, particularly in Hispanic populations.MethodsWe conducted a retrospective cohort study of adults (≥18 years) with biopsy-proven LN from tertiary centers in Colombia (2011-2024). The exposure was LN at SLE onset (LNSO), defined as LN diagnosed concurrently with SLE or with kidney biopsy within 30 days of SLE onset, versus LN occurring later (non-LNSO). The primary outcome was end-stage kidney disease (ESKD), defined as sustained eGFR <15 mL/min/1.73 m[2] for ≥3 months, chronic dialysis, or kidney transplantation. Secondary outcomes were all-cause mortality and a composite of ESKD, death, or doubling of creatinine. Associations were estimated using cause-specific Cox and Fine-Gray models. A 180-day landmark analysis assessed the impact of no remission at 6 months.ResultsAmong 428 patients, 281 (65.7%) had LNSO and 147 (34.3%) non-LNSO. Median follow-up was 5.3 years. ESKD occurred in 72 patients (16.8%) and did not differ by LNSO status (log-rank p = 0.278). LNSO was not associated with ESKD (adjusted HR 0.87; 95% CI 0.48-1.60) or in competing-risk models (sHR 0.85; 95% CI 0.19-3.84). Lower baseline eGFR, higher NIH chronicity index, and higher non-renal damage were associated with ESKD. The composite outcome occurred in 156 patients and was not associated with LNSO. No remission at 6 months strongly predicted adverse outcomes.ConclusionsLNSO was not independently associated with kidney or survival outcomes. Baseline function, chronicity, non-renal damage, and early response were the main prognostic factors.

BackgroundSystemic lupus erythematosus (SLE) is characterized by chronic systemic inflammation, frequent corticosteroid exposure, and heightened cardiometabolic vulnerability. Metabolic syndrome (MetS) has become a clinically significant comorbidity among individuals with SLE. We performed an updated systematic review and meta-analysis to better understand the prevalence and identify the factors associated with the occurrence of MetS in SLE.MethodsPubMed, Scopus, and Web of Science were systematically searched through January 4, 2026 to identify observational studies reporting the prevalence of MetS among individuals with SLE. Random-effects meta-analytic models were applied to calculate pooled prevalence estimates and evaluate the associations with potential risk factors.ResultsThe overall pooled prevalence of MetS in patients with SLE was estimated at 0.27 (95% CI: 0.24-0.30). Sex-stratified analyses showed a prevalence of 0.36 (95% CI: 0.25-0.47) in male patients and 0.27 (95% CI: 0.23-0.30) in female patients. Across continents, the highest prevalence was observed in Africa (0.36, 95% CI: 0.30-0.41), followed by South America (0.32, 95% CI: 0.24-0.40), Asia (0.27, 95% CI: 0.22-0.32), Europe (0.23, 95% CI: 0.18-0.28), and North America (0.21, 95% CI: 0.14-0.30). Regarding medication use, hydroxychloroquine was associated with a significantly reduced risk of MetS (OR = 0.66, 95% CI: 0.52-0.83; P < 0.01), whereas cyclophosphamide (OR = 1.39, 95% CI: 1.06-1.81; P = 0.02), azathioprine (OR = 1.25, 95% CI: 1.00-1.55; P = 0.04), and mycophenolate mofetil (OR = 1.13, 95% CI: 1.03-1.23; P = 0.01) were each associated with a significant increased risk of MetS. No significant associations were found for steroids (OR = 1.34, 95% CI: 0.97-1.83; P = 0.07), methotrexate (OR = 1.07, 95% CI: 0.78-1.47; P = 0.84), or cyclosporine use (OR = 1.19, 95% CI: 0.64-2.21; P = 0.33). The analysis also identified several risk factors for MetS in SLE patients. Patients with MetS were older (Hedges' g = 0.47; P < 0.01), had higher BMI (Hedges' g = 0.88; P < 0.01), and higher total cholesterol (Hedges' g = 0.39; P < 0.01) and LDL levels (Hedges' g = 0.41; P < 0.01) than those without MetS.ConclusionMetS is prevalent among individuals with SLE and is influenced by demographic, clinical, and treatment-related factors. These findings highlight the need for targeted monitoring and management strategies to reduce the cardiometabolic risk in this population.

ObjectivesTo explore pregnancy-related concerns among women with systemic lupus erythematosus (SLE) and impact of the disease on desired family size.MethodCross-sectional, single-center study, including women with SLE diagnosed before menopause. Data were collected via questionnaires and medical records. Participants were classified into three groups: (i) those who never conceived (Group 1); (ii) those who had conceived before SLE diagnosis (Group 2), and (iii) those who had conceived at least once after disease diagnosis (Group 3). Continuous variables were analyzed using Kruskal-Wallis with Mann-Whitney U post-hoc tests; categorical variables using Chi-square or Fisher's exact tests.Results152 patients were included and 75% had received information from their treating physician on reproductive health. Most common pregnancy-related concerns were the need to receive medication during pregnancy (56.6%), followed by concerns about pregnancy complications (53.9%). Women in Group 1 were younger and mainly attributed not having children to personal choice and not to SLE (56.4%). In contrast, women in Groups 2 and 3 frequently reported having fewer children than desired (35.3% and 44.6%, respectively), mostly due to SLE-related concerns (83.3% and 86.2%, respectively). In Group 3, deviation from desired family size was smaller among women who conceived in more recent periods (2015-2024, 32%), although attribution of deviations to SLE remained high.ConclusionsSLE affects women's reproductive decisions, underscoring the importance of tailored counseling.

ObjectiveWhile triple antiphospholipid antibody (aPL) positivity is associated with a higher risk of thrombosis, the clinical significance of single aPL positivity remains unclear. This study aimed to assess the prevalence, clinical characteristics, and cardiovascular disease (CVD) risk profile of persistently single aPL-positive primary antiphospholipid syndrome (PAPS) patients.MethodsWe conducted a retrospective analysis for APS patients from the APS ACTION registry with confirmed persistent single aPL positivity (after testing for lupus anticoagulant [LA], anticardiolipin [aCL] IgG/IgM, or anti-β2-glycoprotein I [aβ2GPI] IgG/IgM), defined by the Revised Sapporo APS Classification Criteria. Triple aPL-tested single aPL-positive patients with no APS classification were used as a control group. Demographics, clinical characteristics, aPL profiles, and adjusted Global APS Score (aGAPSS) were compared between two groups.ResultsAmong 233 PAPS patients tested, 84 (36%) had single aPL positivity: 67 (79%) LA positive, eight (10%) aCL IgG or IgM positive, and 9 (11%) aβ2GPI IgG or IgM positive. Among 97 aPL-positive patients with no APS classification, 22 (22.7%) had single aPL-positivity: nine LA positive, eight aCL IgG or IgM positive, and 5 aβ2GPI IgG or IgM positive. Single LA positivity was significantly more common in PAPS patients, whereas aCL IgM or aβ2GPI IgM positivity were significantly more common in those without APS classification. Historical thrombosis recurrence was observed in 26% of single aPL-positive PAPS patients, predominantly among those with LA positivity (86%).ConclusionsIn this international cohort of persistently aPL-positive individuals, 36% had single aPL positivity, mostly positive LA test. Although "single" aPL-positivity is traditionally considered as a lower-risk profile, findings highlight the importance of differentiating between single LA-positivity and single aCL/aβ2GPI positivity, and the need for individualized risk stratification.

ObjectiveTo describe the operational criteria and characterize the referral outcomes of a structured primary care-led clinical triage pathway for systemic lupus erythematosus (SLE), implemented by a family physician with postgraduate training in rheumatology.MethodsWe conducted a retrospective observational study including 148 adult patients with confirmed SLE managed between January 2025 and January 2026 at SERVIMED IPS, Colombia. The structured triage pathway was in active clinical use throughout the study period. For the purposes of this analysis, patients were classified into a four-level triage framework with predefined clinical and laboratory criteria for each management tier (continued primary care, programmed referral, prioritized referral, and urgent referral) by applying those criteria retrospectively to documented clinical and laboratory records. Primary outcomes included time to rheumatology assessment and indications for referral.ResultsOf 148 patients (84.5% female; median age 38 years), 93 (62.8%) required rheumatology consultation (38 programmed, 55 prioritized) and 19 (12.8%) required urgent referral. Median time to rheumatology assessment was 22 days (IQR 15-31) for prioritized and 49 days (IQR 38-62) for programmed referrals. Urgent referrals were evaluated within a median of 2 days (IQR 1-3). Newly diagnosed patients were more frequently classified at Level 3 than established patients (56.5% vs 28.4%). Triage reclassification occurred in a minority of cases. SLEDAI-2K was available in 92 patients (median 6, IQR 4-10).ConclusionsA structured primary care-led triage pathway with explicit operational criteria provides a descriptive framework for risk-stratified referral to rheumatology care for patients with SLE in resource-constrained settings. The observed referral times are preliminary descriptive findings that warrant prospective comparative evaluation. Formal inter-rater reliability assessment and independent validation studies are needed before broader implementation recommendations can be made.

Systemic Lupus Erythematosus (SLE) is a chronic illness characterized by unpredictability, which increases the risk of experiencing uncertainty in illness. The literature suggests that uncertainty in illness decreases psychological adjustment to illness in several chronic conditions. The purpose of this cross-sectional descriptive study was to explore the relationship between uncertainty in illness and psychological adjustment to illness in individuals diagnosed with SLE. Patients with a diagnosis of SLE were invited to complete an anonymous battery of online questionnaires assessing uncertainty in illness, psychological adjustment, quality of life, and social determinants of health factors. Uncertainty in illness was found to be positively correlated with depression and anxiety. These findings suggest that uncertainty in illness increases the risk of experiencing symptoms related to anxiety and depression among individuals diagnosed with SLE. Further, it is crucial that individuals diagnosed with SLE receive regular screening for symptoms related to depression and anxiety.

ObjectivesThis study aimed to explore the clinical characteristics of patients with late-onset systemic lupus erythematosus (SLE) during the initial stage of disease onset and to evaluate disease activity.MethodData from patients with SLE whose disease onset was ≤3 months were retrospectively collected, and the patients were classified into the late- and early-onset SLE groups based on an age cutoff of 50 years.ResultsThis study included 145 patients, including 31 with late-onset SLE and 114 with early-onset SLE. Compared with the early-onset SLE group, the late-onset SLE group had a lower prevalence of rash (25.8% vs. 45.6%, p = 0.040) and anti-dsDNA antibody positivity (54.8% vs. 72.5%, p = 0.027), whereas pericarditis was more frequent (29.0% vs. 12.3%, p = 0.047) and the C3 levels were higher (0.640 [0.400, 0.892] g/L vs. 0.460 [0.324, 0.701] g/L, p = 0.018). As regards disease activity, the SLEDAI 2000 was 10 (8, 20) in the late-onset SLE group and 15 (10, 22) in the early-onset SLE group (p = 0.066), whereas the SLE-DAS was similar between the groups (13.33 [11.50, 28.45] vs 15.48 [8.56, 25.18], p = 0.744). More than half of patients with late-onset SLE received high-dose or intravenous pulse corticosteroid therapy, with no statistically significant difference compared with patients with early-onset SLE.ConclusionsPatients with very early-stage late-onset SLE exhibited distinct clinical and serological features. However, their disease activity was essentially consistent with that of early-onset SLE, and they often require intensive immunosuppressive therapy.

ObjectiveThis study aimed to assess the relationship between the neutrophil-to-lymphocyte ratio (NLR) and systemic lupus erythematosus (SLE), with specific focus on the association between NLR and disease activity, including lupus nephritis (LN), and evaluating the correlation between NLR and the SLE Disease Activity Index (SLEDAI).MethodsA systematic search of MEDLINE, Embase, and Web of Science from database inception through August 2025 was conducted. Meta-analyses compared NLR values between SLE patients and healthy controls, between active and inactive SLE, and between active LN and non-LN subgroups, with stratification by ethnicity, sample size, and publication year. Correlation coefficients between NLR and SLEDAI were pooled to assess the strength of this association.ResultsThirty-one studies comprising 4,006 SLE patients and 2,576 healthy controls were included. The combined analysis showed significantly increased NLR in SLE patients versus controls (SMD = 1.051, 95% CI = 0.817-1.286, p < 0.001). Significantly higher NLR was observed in European, Asian, and Arab SLE patients relative to healthy controls within each respective subgroup, by showing significantly higher NLR in European (SMD = 1.058, 95% CI = 0.402-1.713, p = 0.002), Asian (SMD = 1.058, 95% CI = 0.839-1.278, p < 0.001), and Arab (SMD = 1.127, 95% CI = 0.707-1.547, p < 0.001) populations. Comparing disease activity, active SLE patients had notably higher NLR than those with inactive disease (SMD = 1.134, 95% CI = 0.252-2.017, p = 0.012). However, the difference in NLR between active LN and non-LN groups was not statistically significant (SMD = 0.467, 95% CI = -0.045-0.979, p = 0.074). NLR showed a significant positive correlation with SLEDAI (correlation coefficient = 0.354, 95% CI = 0.256-0.444, p < 0.001). Subgroup analysis revealed significant correlations in Asian (correlation coefficient = 0.358, 95% CI = 0.246-0.461, p < 0.001) and Arab (correlation coefficient = 0.525, 95% CI = 0.382-0.644, p < 0.001) populations.ConclusionsThis meta-analysis demonstrates that NLR is significantly increased in SLE patients compared to healthy controls, and that NLR is associated with greater disease activity, supported by its positive correlation with SLEDAI.