ObjectiveImmune complexes (ICs) play a central role in the pathogenesis of systemic lupus erythematosus (SLE). We previously showed that detectable ICs predicted clinical remission off corticosteroids (CR off C), also referred to as glucocorticoid-free clinical remission. Because the C1q-based IC assay is no longer commercially available in Japan, we aimed to identify clinical and serological predictors of IC detection, develop a simple score, and explore the association between this score and CR off C.MethodsWe retrospectively evaluated two cohorts derived from patients with active SLE treated at a single center. The evaluation cohort included patients followed for ≥ 1 year to assess CR off C, whereas the derivation cohort consisted of patients who had circulating ICs measured. Logistic regression with Firth correction was used to identify independent baseline predictors of IC detection. These factors were then used to develop an exploratory score for IC detection. The association between the score and CR off C was assessed using Kaplan–Meier analysis and Cox proportional hazards modeling.ResultsAmong the evaluation cohort (n = 70), 34% achieved CR off C during a median follow-up of 4.4 years. In the derivation cohort (n = 61), three independent predictors of IC detection were identified: anti-dsDNA antibody ≥ 57.5 IU/mL, low C3 (<68.5 mg/dL), and male sex. A three-factor score (0–3 points) showed increasing frequencies of IC detection (0: 6.3%; 1: 11.8%; 2: 91.7%; 3: 100%) and was associated with achievement of CR off C (log-rank p = 0.04; crude hazard ratio per factor 1.71, 95% CI 1.04–2.80).ConclusionA simple three-factor score was associated with IC detection and a higher likelihood of achieving CR off C in our cohort of patients with SLE. In settings where direct measurement of ICs is unavailable, this score may serve as a potential surrogate for identifying patients likely to have detectable ICs and for assessing their likelihood of achieving glucocorticoid-free clinical remission.
Systemic lupus erythematosus (SLE) is one of the most challenging diseases to manage due to its high heterogeneity and unpredictable course. Rituximab is an off-label, widely administered treatment in severe, refractory SLE. Observational and real-world evidence studies have been highly heterogeneous, featuring differences not only in patient numbers and follow-up periods, but also in evaluation timepoints, ranging from 6 months to longer than 10 years. Despite such methodological issues, rituximab treatment has demonstrated significant efficacy among different disease manifestations, with an acceptable toxicity profile. Therefore, it has become common practice to administer rituximab in patients with SLE after conventional treatments have extensively failed; in such refractory patients, this approach has produced encouraging results. Current evidence suggesting early rituximab introduction is limited; however, preliminary results are promising. In this review, we discuss when, how, and in which patient subgroups rituximab treatment may represent a reasonable approach.
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune dysregulation and persistent inflammation. Although the prognosis of patients with SLE has improved substantially over the past few decades, these patients remain at markedly increased risk of cardiovascular disease (CVD) and major adverse cardiovascular events (MACE) compared with the general population. This excess risk is not fully explained by traditional cardiovascular risk factors captured by the Framingham Risk Score (FRS). Emerging evidence suggests that SLE disease activity, cumulative organ damage, medication exposure, and the presence of antiphospholipid antibodies (aPL) contribute significantly. In this review, we examine studies that have investigated these risk factors, including proposals to adopt alternative risk scores and mechanisms underlying the accelerated atherosclerosis in SLE. We also summarize evidence on the role of hydroxychloroquine, statins, acetylsalicylic acid (ASA) and emerging therapies such as sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 (GLP-1) agonists in mitigating cardiovascular risk. Current challenges include the lack of reliable strategies to identify high-risk patients and limited understanding of the pathophysiologic mechanisms driving accelerated atherosclerosis. Addressing these gaps is critical to developing more effective therapeutic strategies, alongside aggressive management of both traditional and non-traditional risk factors, to reduce the burden of CVD in SLE.
Anifrolumab, a monoclonal antibody against the type I interferon receptor, has shown efficacy in systemic lupus erythematosus (SLE). However, sustained remission after drug discontinuation has been rarely reported. We reported two females with SLE who achieved biologic-free clinical remission after discontinuation of anifrolumab, with no major adverse events observed during or after treatment. Case 1: A 25-year-old woman with newly diagnosed SLE presented with active disease (SLEDAI-2K 14), including arthritis, facial rash, alopecia, mucosal ulcers, hypocomplementemia, and anti–double-stranded DNA antibody positivity. She was initially treated with prednisolone (PSL) and hydroxychloroquine (HCQ); however, a flare occurred during glucocorticoid (GC) tapering, and anifrolumab was initiated with concomitant methotrexate (MTX). The patient achieved clinical remission according to the Definition of Remission In SLE (DORIS) criteria, despite persistent hypocomplementemia and anti–dsDNA antibody positivity. After sustained remission, PSL was discontinued, MTX was tapered, and anifrolumab was discontinued after 25 months due to sustained clinical remission according to the DORIS criteria and patient preference related to work-related difficulty with long-term regular follow-up. She has remained in clinical remission for 6 months on HCQ and low-dose MTX. Case 2: A 22-year-old woman with SLE diagnosed at age 16 presented after disease relapse following GC withdrawal at age 21. At relapse, her disease activity was moderate (SLEDAI-2K 11), characterized by facial rash, alopecia, mucosal ulcers, leukopenia, hypocomplementemia, and anti–dsDNA positivity. She was treated with anifrolumab in combination with HCQ. Her disease activity achieved and maintained clinical remission according to the DORIS criteria, despite persistent hypocomplementemia and anti–dsDNA antibody positivity. Dose spacing and subsequent discontinuation of anifrolumab were attempted because of patient preference related to work-related limitations to long-term follow-up, and future pregnancy plans, and sustained remission was maintained. Even after switching to tacrolimus (Tac), she has maintained remission without anifrolumab for 12 months. These cases suggested that clinical remission could be maintained after discontinuation of anifrolumab in selected patients with SLE.
IntroductionNeutrophil extracellular traps (NETs) are increasingly recognized as having important roles in autoimmune disease pathogenesis. In many autoimmune diseases, e.g., rheumatoid arthritis (RA) and lupus (SLE), premenopausal women have increased incidence. Understanding immunologic effects of exposures common in premenopausal women, such as oral contraceptive pill (OCP) use, is important to understanding autoimmune disease risk in women. We investigated the relationship between OCP use and circulating calprotectin, a NETosis marker relevant to autoimmune disease pathogenesis.Methods164 samples from healthy premenopausal women (65 current OCP users; 99 never/prior users) and 124 samples from premenopausal women at-risk for RA by family history (57 current OCP users; 67 never/prior users) were tested for plasma calprotectin levels by ELISA. Levels were compared between current and never/prior users via Welch's T-test.ResultsHealthy women currently taking OCPs had lower plasma calprotectin levels than never/prior OCP users in both the derivation (0.99 µg/mL vs. 1.38 µg/mL, p = 0.016) and validation (0.9 µg/mL vs. 1.4 µg/mL, p = 0.001) cohorts. Similarly, in women at-risk for RA, current OCP users had lower plasma calprotectin level compared to never/prior users (1.19 µg/mL vs. 1.74, p = 0.017).DiscussionCurrent OCP use is associated with significantly lower plasma calprotectin in healthy premenopausal women and premenopausal women at-risk for RA. Given calprotectin is considered a NETosis marker and NETosis is associated with pathogenesis in several autoimmune diseases, our findings suggest a reduction in NETosis via OCP use could be a potential mechanism influencing autoimmune disease in premenopausal women.
BackgroundImmune dysregulation years prior to a clinical diagnosis of systemic lupus erythematosus (SLE) may include a range of asymptomatic autoantibody positivity to clinically evident disease. The effect of this spectrum of immune dysregulation on pregnancy outcomes, including pregnancies in women prior to a diagnosis of SLE, is poorly understood. We sought to identify associations of adverse pregnancy outcomes across groups along this spectrum.MethodsUtilizing a large longitudinal cohort at a single center, we evaluated pregnancy outcomes among the following four groups: antinuclear antibody (ANA) negative controls, ANA-positive controls, pregnancies before a diagnosis of SLE, and pregnancies after a diagnosis of SLE. The pregnancy outcomes considered were live birth rate, preeclampsia, low birth weight, premature birth, spontaneous abortion, and stillbirth. Generalized estimating equation models were used to evaluate key associations and confounders.ResultsWe included 811 participants and 2,209 pregnancies. Of these, 198 participants were ANA-positive controls and 369 were diagnosed with SLE, with their first pregnancy occurring before diagnosis. Overall, 81.5% self-identified as Black and 31% had resided in areas with high social vulnerability. The median number of pregnancies between the groups was similar, with the majority of participants having at least one live birth. The lowest median number of pregnancies occurred in the pregnancy after SLE diagnosis group. The adverse outcome rate did not differ between the ANA-positive and ANA-negative controls. The risk of any adverse outcome was greatest in those with pregnancies after an SLE diagnosis [OR (95% CI): 3.33 (2.35, 4.71)], but was also increased in those with pregnancies before a diagnosis of SLE as compared to the ANA-positive controls [OR (95% CI): 1.78 (1.28, 2.47)]. When grouped by time prior to diagnosis, the risk of any adverse outcome remained increased in pregnancies occurring both 2–5 years or greater than 5 years prior to SLE diagnosis as compared to the ANA-positive controls [OR (95% CI): 1.64 (1.01, 2.67) and OR (95% CI): 1.65 (1.17, 2.32), respectively].ConclusionThe risk of adverse pregnancy outcomes appears to increase along the SLE spectrum, with the highest risk occurring after diagnosis. ANA positivity alone is not sufficient to impact pregnancy outcomes.
BackgroundFertility remains a controversial issue in women with systemic lupus erythematosus (SLE); it is largely preserved, though a subset experiences subfertility due to multiple interacting factors. Small studies on anti-mullerian hormone (AMH) as an ovarian reserve marker in SLE have yielded conflicting results; data on antral follicular count (AFC) and ovarian volume (OV) are sketchy. Potential ethno-geographic differences exist, but there is no data on ovarian reserve of Indian lupus patients. There is lack of clarity on the factors affecting ovarian reserve in SLE.MethodsIn this single-centre observational study, female SLE patients aged 18–45 years were tested for AMH, FSH, and estradiol at D2–D5 of menstrual cycle. Ultrasonographic assessment of AFC and OV was done in a subset. Age-specific nomograms of AMH and AFC of healthy fertile women were used for comparison. Proportion of patients with premature ovarian insufficiency (POI), early menopause, and those having low AMH (<1 ng/mL) were calculated. Clinico-immunological determinants of reduced ovarian reserve were identified through multivariable logistic regression.Results168 lupus women [mean age 27(6.4) years] were included. 93(55%) were married. 120(72%) had regular menstrual cycles. 3(1.8%) had POI (at 21, 22, and 37 years of age), while an additional two (1.2%) had early menopause at 41 and 44 years. 82(49%) were found to have low AMH. Comparison with age-specific nomograms showed 64% patients had AMH and 47% had AFC less than the corresponding tenth centile of healthy fertile women. Multivariable regression showed higher age [OR = 1.12(1.05–1.20), p = 0.001], active disease [OR = 3.87(1.56–9.62), p = 0.004], menstrual irregularities [OR = 4.56(1.95–10.65), p < 0.001], and anti-Ro60 positivity [OR = 1.89(0.92–3.88), p = 0.08] independently predicted reduced AMH. There was no association with organ involvement (including nephritis), disease duration, anti-dsDNA, anti-Sm, or aPL positivity, or prior CYC use.ConclusionsPrevalence of POI and early menopause in our study was found to be 1.8% and 1.2%, respectively. A high proportion (49%) of Indian SLE patients had evidence of low ovarian reserve in the absence of known risk factors. Higher age, active disease, menstrual irregularities, and anti-Ro60 positivity were found to be independently associated with diminished ovarian reserve. No association was found with prior CYC use, nephritis, or antiphospholipid antibodies.
BackgroundBelimumab is used as add-on therapy in patients with refractory systemic lupus erythematosus (SLE). While shared features guide patient eligibility, whether clinical and laboratory variables may identify distinct candidate subgroups remain unclear.AimTo identify clinical clusters among SLE patients initiating belimumab and assess their relationship with clinical outcomes.MethodsData were derived from the Italian multicentric Lupus Italian REgistry (LIRE), including patients starting belimumab added to standard treatment. Factor Analysis of Mixed Data (FAMD) with 150 baseline variables was followed by Hierarchical Clustering on Principal Components using Ward's criterion and Euclidean distance to define clusters. Disease activity was assessed by SLEDAI-2 K, damage by SLICC Damage Index (SDI), and clinical response as cSLEDAI-2K = 0 at 6 and 12 months (T6, T12).ResultsAmong 125 patients, clustering identified four main groups. Cluster 1 (n = 55) exhibited lower SDI; Cluster 2 (n = 28) included patients with renal involvement (p < 0.001); Cluster 3 (n = 14) displayed neuropsychiatric/cardiovascular activity, highest baseline SDI (p = 0.006), enriched neurological/cardiovascular damage (p < 0.001), and lowest hydroxychloroquine use (78.6% vs. 95.2%, p = 0.05); Cluster 4 (n = 28) showed predominant hematological abnormalities. Clinical responses were comparable across clusters, though Cluster 2 showed numerically higher cSLEDAI-2K = 0 rates at T12 (70.8% vs. 52.3%, p = 0.082). Final SDI was highest in Cluster 3 (p < 0.01), while damage accrued faster in Cluster 1 [0 (0–2) vs. 1 (1, 2), p < 0.001].ConclusionUnsupervised clustering revealed clinical heterogeneity among belimumab-treated SLE patients. Renal/serologically active profiles showed a numerically higher response rate, whereas pre-existing damage and low hydroxychloroquine use associated with higher damage burden despite biologic therapy.
The postpartum period represents a critical and underexplored phase in the reproductive course of women with systemic autoimmune diseases (SAD). While advances in disease management have substantially improved pregnancy outcomes, the weeks and months after delivery remain associated with a significant burden of maternal complications. Abrupt immunological and hormonal changes, together with treatment modifications during pregnancy and breastfeeding, may predispose women with SAD to disease reactivation and other adverse outcomes after delivery. This Mini Review summarizes the available evidence on postpartum complications in women with SAD, with a focus on disease flares, thrombotic and infectious events, mental health and quality of life, and therapeutic challenges during lactation. Despite its clinical relevance, postpartum outcomes remain insufficiently investigated, with limited prospective data, heterogeneous endpoints, and gaps between clinical recommendations and real-life practice. Recognizing the postpartum period as a distinct and integral component of reproductive health is essential to improve maternal outcomes and optimize long-term care for women with SAD.
IntroductionSystemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder characterized by aberrant immune activation, autoantibody production, immune complex deposition, and progressive organ damage, particularly lupus nephritis. Developing therapies that can simultaneously modulate immune dysregulation and inflammation remains a major clinical need.MethodsIn the present study, we evaluated the therapeutic efficacy of the antimicrobial and immunomodulatory peptide SK1217 in a pristane-induced lupus mouse model. Disease progression and therapeutic effects were assessed through measurement of serum autoantibodies, proinflammatory cytokines, complement levels, renal function markers, and immune cell populations. Molecular mechanisms were investigated by analyzing MAPK and NF-κB signaling pathways in renal tissues.ResultsSK1217 treatment significantly reduced serum autoantibody levels, including anti-dsDNA, anti-ssDNA, anti-chromatin, anti-ANA, and anti-nRNP antibodies. The peptide also suppressed proinflammatory cytokines TNF-α, IL-1β, IL-6, and IL-17. Mechanistically, SK1217 attenuated activation of inflammatory signaling pathways, as demonstrated by reduced phosphorylation of JNK and p38 MAPK and downregulation of NF-κB p65. SK1217 further modulated humoral immune responses by decreasing serum BAFF levels and altering splenic CD40+ activated B cells and CD138+ plasma cell populations, accompanied by reduced total serum IgG levels. Complement balance was restored through normalization of serum C3 levels. Functionally, SK1217 improved renal parameters by reducing urinary protein excretion, serum creatinine, and blood urea nitrogen levels, and ameliorated glomerular pathology. Additionally, the peptide modulated immune cell dynamics by reducing Ly6Chi monocytes and regulating peritoneal macrophage and granulocyte populations.DiscussionCollectively, these findings demonstrate that SK1217 exerts multi-target immunomodulatory and renoprotective effects through coordinated suppression of BAFF-driven B cell activation, inflammatory cytokine production, complement activation, and MAPK/NF-κB signaling pathways. These results highlight SK1217 as a promising therapeutic candidate for SLE and lupus nephritis, warranting further translational investigation.
Systemic lupus erythematosus (SLE) poses diagnostic and management challenges to physicians given its protean manifestations and complex immune dysregulation. Numerous drugs are used in the management of lupus with a plethora under investigation for more effective, safe, and targeted therapies. This narrative review explores recent literature on the safety and efficacy multiple drug classes and gene therapy under investigation in the management of SLE. The findings in this review detail which new candidate drug and gene therapies are showing efficacy and safety in SLE management, and which are not.
IntroductionObstetric antiphospholipid syndrome (OAPS) is an autoimmune disorder associated with pregnancy morbidity, including recurrent pregnancy loss, preeclampsia and fetal growth restriction. Despite standard of care (SoC) with low-dose aspirin (LDA) and low-molecular-weight heparin (LMWH), 20%–30% of pregnancies still result in adverse outcomes. The 2023 ACR/EULAR classification criteria have improved research standardisation, yet robust clinical evidence, including randomised controlled trials (RCTs), remains limited and current management largely relies on empirical practice and RCTs performed nearly two decades ago.MethodsIn this mini-review, with a particular focus on refractory OAPS, we summarise the quality of evidence and methodological limitations underpinning current therapeutic strategies. This included existing SoC and potential adjuvant treatments, such as hydroxychloroquine (HCQ), corticosteroids, statins, intravenous immunoglobulin (IVIG) and biologics.ResultsLDA and LMWH remain the cornerstone of OAPS care. Observational data suggest that HCQ may enhance live birth rates in refractory cases, while glucocorticoids offer limited benefit and pose maternal risks. Evidence for IVIG, statins, and biologics is sparse and primarily derived from small uncontrolled studies. With the exception of a few trials reported almost two decades ago, no RCTs have been conducted specifically in OAPS.DiscussionImproved management of OAPS requires higher-quality evidence. Trials in other high-risk pregnancy populations demonstrate that RCTs are feasible. Progress will depend on standardised pregnancy outcome measures, international collaboration with coordinated leadership and increased societal and regulatory recognition of the urgent need for research and funding.This mini-review synthesizes current knowledge on the treatment of refractory OAPS, identifies critical research gaps, and outlines key strategic elements needed to advance evidence-based care for this high-risk population.
Scavenger receptors (SRs) play an important role in the innate immune response by recognizing and binding a variety of ligands to initiate the removal of both altered self- and non-self-antigens. Over the last two decades, SRs have become a forefront for their role influencing and contributing to inflammatory disease pathways. The findings discussed in this review show that the immunological role SRs play is (1) found in multiple organ systems and not limited to one disease or subset of symptoms; (2) part of both the innate and adaptive immune response in addition to influencing inflammatory signaling via non-immune cell subtypes; (3) both pro- or anti-inflammatory depending on which SR class or cell signaling pathway is being observed; (4) potentially useful for the development of therapeutics and diagnostic or prognostic biomarkers for autoimmune disease pathology. Understanding the role of SRs in the context of inflammation and autoimmunity will shed some light on the comprehension of heterogeneous diseases, such as Systemic Lupus Erythematosus.
Sjögren's disease (SjD) and systemic lupus erythematosus (SLE) are distinct autoimmune disorders and their clinical overlap presents a unique immunological entity with specific challenges. While the clinical manifestations of the SjD-SLE overlap have been extensively characterised, its underlying pathogenetic mechanisms remain less understood. This review underscores the immunological features of the overlap, highlighting the roles of genetic predisposition, interferon pathway activation and B-cell dysregulation. Key genetic factors, particularly those associated with HLA and cytokine signaling, underpin disease susceptibility by promoting aberrant immune responses. The consequent and persistent interferon pathway activation drives chronic inflammation and establishes a feedback loop with autoantibody production. Furthermore, Extrafollicular B-cell responses are central to generating hallmark autoantibodies, such as anti-dsDNA and rheumatoid factor, which are frequent in the overlap. Finally, the continuous activation of interferons and B-cells not only increase disease activity but also contributes to lymphoproliferative complications. Despite progress in elucidating these mechanisms, patients with SjD-SLE overlap remain underrepresented in clinical trials, limiting therapeutic advancements. Emerging strategies, including interferon receptor inhibitors, BAFF-blocking antibodies, and advanced B-cell depletion therapies, may offer promising options to hit the distinct immunological abnormalities of these patients.
Cutaneous lupus erythematosus (CLE) is a group of skin disorders where the immune system attacks skin cells. CLE can affect people who have systemic lupus erythematosus, or can occur independently. In prior studies, CXCL16 and its primary receptor, CXCR6, have been shown to be elevated at the RNA or protein level in different organs that are affected by lupus. In this systematic review, we sought to understand whether CXCR6 and its ligand CXCL16 could serve as biomarkers for lupus skin or other organ involvement. Our search strategy and protocol are registered on Prospero under # CRD42024583076. CXCL16 was shown to be a biomarker of lupus nephritis and disease activity in both urine and serum samples in multiple studies. CXCL16 was also elevated in cerebrospinal fluid in neuropsychiatric lupus patients as well as other autoimmune brain conditions. Last, we queried publicly available datasets and our own datasets to evaluate expression of CXCR6 and CXCL16 in lupus skin. CXCR6 but not CXCL16 was enriched in lupus skin across multiple datasets and model organisms. Taken together, our study corroborates the CXCR6 chemokine family as a potential biomarker of lupus organ involvement.
Pregnancy complications from maternal placental syndrome (MPS) are associated with the accelerated development of cardiovascular events (CVE) in the parous cohort with systemic lupus erythematosus (SLE). Preterm birth may result from MPS, which is more common in SLE. This study aimed to determine if preterm birth stratified by gestational age increases the risk of CVE in SLE. Utilizing Swedish population databases between 1973 and 2011, those who had been pregnant with SLE were identified and stratified into three groups: term (≥37 + 0 weeks), late preterm 34 + 0–36 + 6 weeks, and early preterm <34 + 0weeks births. The primary outcome was CVE or death from CVE. The risk of CVE was calculated and adjusted for SLE-related morbidity and cardiovascular risk factors. Over the 38-year interval, there were 3,963 subjects, and the prevalence of preterm birth was 20.9%. The prevalence of CVE was 10.4% (n = 411), being highest in those who had given birth <34 + 0 weeks. After multivariable adjustment, the risk of CVE was 1.8 [adjusted hazards ratio (HR) 95% CI: 1.3–2.5] in those who birthed <34 + 0 weeks compared with others who had birthed at term. They also developed CVE earlier than those who birthed at later gestational ages. Early preterm birth <34 + 0 weeks conferred a two-fold increased hazard for accelerated development of CVE. Reassuringly, those who delivered at a later gestation did not exhibit a similar risk of premature CVE. Therefore, birth <34 + 0 weeks, regardless of an underlying cause, may be a useful screening question to identify parous persons with SLE who are at greater risk of early CVE.
Atherosclerosis is increasingly recognized as a chronic inflammatory process, involving intricate interactions among the endothelium, lipids, coagulation system, and components of both the innate and adaptive immune systems. In the context of systemic lupus erythematosus (SLE), these interactions are even further disrupted, contributing to accelerated atherosclerosis. This narrative review explores how immune system dysregulation plays a central role in the development of atherosclerosis in SLE patients, where cardiovascular disease remains the leading cause of mortality despite recent advancements. We aim to present a model based on current scientific evidence that compares the immune mechanisms driving atherosclerosis in the general population with the accelerated form observed in SLE patients, highlighting the key immunological distinctions that set SLE-associated atherosclerosis apart. Particular emphasis was given to the interactions between interferon, lipid alterations and adaptive immunity as mediators of atherogenesis. This model may help identify gaps in our understanding and generate new hypotheses for potential therapeutic targets to modulate immune responses within atherosclerotic plaques.
Objectives This study aimed to investigate hemostatic parameters in pregnant patients with systemic lupus erythematosus (SLE) in relation to the use of antithrombotic prophylaxis, preeclampsia (PE), and antiphospholipid antibody status. Patients and methods In total, 34 pregnant patients with SLE and 80 pregnant healthy controls (HC) without PE were included. Patients with SLE were sampled during the first and third trimester of gestation. We analyzed fibrinogen, D-dimer, and global hemostatic parameters including the overall coagulation potential (OCP), overall hemostatic potential (OHP), and the overall fibrinolysis potential (OFP). Fibrin structure was visualized using scanning electron microscopy. Results The median age of the patients with SLE was 33 (range 23–42) years and 31 (26–38) years in the HC. The median disease duration was 10 (range 0–26) years. All but two patients with SLE received prophylaxis with low-dose acetylsalicylic acid (LDASA) and 11 received low-molecular-weight heparin (LMWH). OCP and OHP were significantly increased in the patients with SLE compared to HC ( p < 0.01). The levels of fibrinogen and D-dimer increased throughout the pregnancies in the patients with SLE, but no differences were found in the third trimester compared to controls. Among the patients treated with LMWH, OCP, OHP, and OFP were undetectable in two, both of whom were on high prophylactic dosage, and one developed PE. OCP, OHP, and OFP levels were not affected by low prophylactic doses of LMWH. Despite LDASA, preeclampsia occurred in four patients with SLE (12.5%); of whom two received a high prophylactic LMWH dose. Five of 32 (15.6%) patients had major bleeding complications at delivery. There were no thromboembolic complications. Conclusions In this pilot study, pregnant patients with SLE developed a hypercoagulable state throughout pregnancy, as demonstrated by the global hemostatic parameters OCP and OHP, except for two patients who were treated with a full dosage of LMWH. The alterations in the coagulation system in SLE pregnancy need to be further studied with the aim of optimizing treatment strategies.
ObjectiveRace and region-specific variables influence lupus nephritis clinical features and prognosis. We examined the clinicopathological presentation and long-term kidney outcomes of lupus nephritis in Indonesia.MethodsThis was a retrospective cohort study conducted from 1 January 2011 to 31 December 2021 on biopsy-proven lupus nephritis patients, corresponding to the International Society of Nephrology/Renal Pathology Society 2018 classification. Patients were followed until death, development of end-stage kidney disease, initiation of kidney replacement therapy, or end of study. The association between lupus nephritis class and kidney outcomes was analyzed using cumulative incidence plots. A linear mixed-model analysis was performed to assess the association between lupus nephritis class and kidney function decline.ResultsThis study included 268 patients, with a mean age of 28.7 + 8.5 years, and 94.8% were female. The main histopathological diagnosis was class IV (39.6%). The prescription rate of renin–angiotensin–aldosterone system (RAAS) inhibitors ranged from 0.5% in class VI to 37.4% in class IV (p = 0.138), while that of hydroxychloroquine usage ranged from 0% in class VI to 37.7% in class IV (p = 0.845). Class IV was associated with higher chronic and active lesions, including global (42.6%, p = 0.073) and segmental (41.1%, p = 0.009) glomerulosclerosis; segmental (43.1%, p < 0.001) and global (74.1%, p = 0.004) endocapillary hypercellularity; and sub-endothelial deposit (59.5%, p = 0.007). Over a median follow-up of 26 (IQR = 6.0–48.0) months, 16.4% of patients died, and 3.7% developed end-stage kidney disease or initiated kidney replacement therapy. Infection, including tuberculosis (9.1%), was the leading cause of death. Class IV was associated with a high mortality risk (HR 1.94, p = 0.028), a lower baseline estimated glomerular filtration rate (eGFR) compared with class I/II (β = −51.3, SE = 12.3, p < 0.001), and a less steep decline or even an increase in eGFR over time (β = 15.7, SE = 7.0, p = 0.026).ConclusionsThis cohort demonstrated a high prevalence of chronic lesions, low use of renin–angiotensin–aldosterone system inhibitors and immunosuppressive medications, and notable mortality. This study highlights the importance of timely detection on kidney involvement in SLE patients, routine use of renin–angiotensin–aldosterone system inhibitors, optimal prescription of immunosuppressive medications, and aggressive screening and prophylactic measures of infectious diseases should be encouraged to improve kidney outcomes in lupus nephritis patients in Indonesia.
BackgroundPost traumatic stress disorder (PTSD) is associated with traumatic brain injury (TBI) and autoimmune disease, including systemic lupus erythematosus (SLE). We sought to determine whether the association was related to only PTSD or the combination of PTSD and TBI.MethodsWe studied rheumatic disease autoantibodies in a cohort of 40 patients, 20 of whom had TBI without PTSD and 20 had both PTSD and TBI. None had diagnosed rheumatic autoimmune disease. We also examined a cohort of 229 TBI patients, of whom 60% had PTSD, for diagnosis of rheumatic autoimmune disease.ResultsAmong the 20 subjects with PTSD and TBI, 8 had autoantibodies [1 each with anti-Ro (or SSA), anti-RNP and anti-RNP plus anti-dsDNA, the remainder with a positive ANA]. Only 1 of 20 subjects with TBI alone had autoantibodies (p = 0.0088 by Fisher's Exact test). In the cohort of 229 subjects, there were 92 with TBI but no PTSD, of whom 4 (4.3%) had a diagnosed rheumatic autoimmune disease. Of the 137 with TBI and PTSD, 17 (13.3%) had an autoimmune rheumatic disease (p = 0.02 by Fisher's exact test).ConclusionWe found more autoantibodies in the sera of patients with TBI and PTSD than in TBI alone. In addition, we found a 3-fold increased prevalence of autoimmune rheumatic disease in patients with TBI and PTSD compared to those with TBI alone. TBI is strongly associated with PTSD but we conclude that TBI does not contribute to the increased risk of autoimmune disease in PTSD.
