Manifestations Of Systemic Lupus Erythematosus Research Articles

Association between the Duration of Steroid Therapy with Hyperglycemia in Patients with Systemic Lupus Erythematosus (SLE)

Introduction: Systemic Lupus Erythematosus (SLE) is a systemic autoimmune disease which primary treatment consists of steroid drugs administration. Prolonged steroid administration is often associated with an increase in blood glucose, a condition known as hyperglycemia. Hence, this study aimed to evaluate the association between the duration of steroid therapy with hyperglycemia in patients with SLE treated at a tertiary healthcare center in Surabaya, Indonesia.Methods: A cross-sectional study was conducted under a purposive sampling frame from January to December of 2022 by utilizing secondary data from electronic medical health records in Dr. Soetomo General Academic Hospital, a tertiary healthcare center in Surabaya, Indonesia. The association between variables were analyzed using Fisher’s exact test, chi square test, independent T-test, one-way ANOVA, Mann-Whitney, and Spearman's rank correlation.Results: Out of 150 included patients, 2.67% experienced hyperglycemia following steroid therapy for SLE. There were no significant associations between clinical variables and hyperglycemia occurence in SLE patients (p>0.05). Patients that received higher doses of steroid did not experience any significant difference in hyperglycemia (p=0.727 for <6 months; p=0.865 for ≥6 months). Daily steroid dose was also not significantly associated with the severity of SLE manifestations based on the SLEDAI score (p=0.081). Overall, no significant association was identified between the duration of steroid therapy with hyperglycemia among SLE patients in the hospital (p=0.365). Conclusion: The study found no significant correlation between clinical variables, hyperglycemia incidence, daily steroids dosage, methylprednisolone dosage, SLE severity, or steroid use duration in patients with Systemic Lupus Erythematosus.

Novel mitophagy inducer alleviates lupus nephritis by reducing myeloid cell activation and autoantigen presentation

Lupus nephritis (LN) is one of the most severe manifestations of systemic lupus erythematosus (SLE), but its mechanism of onset remains unclear. Since impaired mitophagy has been implicated in multiple organs in SLE, we hypothesized that mitophagy dysfunction is critical in the development of LN and that pharmacologically targeting mitophagy would ameliorate this disease. Therefore, lupus-prone MRL/MpJ-Faslpr (MRL/lpr) and NZBWF1/J mice were treated with a novel mitophagy inducer, UMI-77, during their onset of LN. This treatment effectively mitigated kidney inflammation and damage as assessed by histology and flow cytometry. Furthermore, dendritic cell (DC)-T cell coculture assay indicated that UMI-77 treatment attenuated DC function that would drive T cell proliferation but did not directly influence the potent T cell proliferation in lupus mice. UMI-77 also restored mitochondrial function and attenuated proinflammatory phenotypes in lupus DCs. Adoptive transfer of DCs from MRL/lpr mice augmented serum anti-dsDNA IgG, urine protein and T cell infiltration of the kidney in MRL/MpJ mice, which could be prevented by either treating lupus donors in vivo or lupus DCs directly with UMI-77. UMI-77 also restored mitochondrial function in myeloid cells from patients with LN in vitro as evidenced by increased ATP levels. Thus, enhancing mitophagy in SLE restrains autoimmunity and limits kidney inflammation for LN development. Hence, our findings suggest targeting mitophagy as a tangible pathway to treat LN.

Antinuclear antibody–associated autoimmune cytopenia in childhood is a risk factor for systemic lupus erythematosus

AbstractAutoimmune cytopenia (AIC) in children may be associated with positive antinuclear antibodies (ANA) and may progress to systemic lupus erythematosus (SLE). We evaluated the risk of progression to SLE of childhood-onset ANA-associated AIC. In the French national prospective OBS’CEREVANCE cohort, the long-term outcome of children with ANA-associated AIC (ANA titer ≥1/160) and a subgroup of children who developed SLE were described. ANA were positive in 355 of 1803 (20%) children with AIC. With a median follow-up of 5.8 (range, 0.1-29.6) years, 79 of 355 (22%) patients developed SLE at a median age of 14.5 (1.1-21.4) years; 20% of chronic immune thrombocytopenic purpura, 19% of autoimmune hemolytic anemia, and 45% of Evans syndrome. None of the patients with ANA-negative test developed SLE. Severe manifestations of SLE were observed in 21 patients, and 2 patients died. In multivariate analysis including patients with positive ANA within the first 3 months after AIC diagnosis, age >10 years at AIC diagnosis (relative risk [RR], 3.67; 95% confidence interval [CI], 1.18-11.4; P = .024) and ANA titer >1/160 (RR, 5.28; 95% CI, 1.20-23.17; P = .027) were associated with the occurrence of SLE after AIC diagnosis. ANA-associated AIC is a risk factor for progression to SLE, especially in children with an initial ANA titer >1/160 and an age >10 years at AIC diagnosis. ANA screening should be recommended in children with AIC, and patients with ANA should be monitored long-term for SLE, with special attention to the transition period. This trial was registered at www.ClinicalTrials.gov as #NCT05937828.

A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile

The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin-3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE.Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.

Lupus enteritis: a narrative review.

Lupus enteritis (LE) is a rare manifestation of systemic lupus erythematosus. The pathophysiology of LE has not been fully elucidated, although inflammatory and thrombotic processes are likely important factors. The underlying pathophysiological mechanisms may depend on which portion of the intestine is affected. Over half of the patients with LE also present with renal or haematological complications. The diagnosis of LE is based on clinical, histopathological and imaging findings; abdominal computed tomography (CT) is the gold standard in diagnosis. Abdominal CT can also identify factors that predict complications and could potentially guide pharmacological and nutritional management. Timely identification and prompt treatment initiation are paramount to avoid life and organ threatening complications. Glucocorticoids are often the first-line treatment. Additional therapy including immunosuppressive therapy is utilised on a case-by-case basis as there are no clinical trials to define the optimal therapeutic approach. Surgical intervention may be needed especially if there is bowel perforation or peritonitis. In general, the prognosis of LE is good.

Proximity extension assay proteomics and renal single cell transcriptomics uncover novel urinary biomarkers for active lupus nephritis

ObjectiveTo identify urinary biomarkers that can distinguish active renal involvement in Lupus Nephritis (LN), a severe manifestation of systemic lupus erythematosus (SLE). MethodsUrine from 117 subjects, comprised of inactive SLE, active non-renal lupus, active LN, and healthy controls, were subjected to Proximity Extension Assay (PEA) based comprehensive proteomics followed by ELISA validation in an independent, ethnically diverse cohort. Proteomic data is also cross-referenced to renal transcriptomic data to elucidate cellular origins of biomarkers. ResultsSystems biology analyses revealed progressive activation of cytokine signaling, chemokine activity and coagulation pathways, with worsening renal disease. In addition to validating 30 previously reported biomarkers, this study uncovers several novel candidates. Following ELISA validation in an independent cohort of different ethnicity, the six most discriminatory biomarkers for active LN were urinary ICAM-2, FABP4, FASLG, IGFBP-2, SELE and TNFSF13B/BAFF, with ROC AUC ≥80%, with most correlating strongly with clinical disease activity. Transcriptomic analyses of LN kidneys mapped the likely origin of these proteins to intra-renal myeloid cells (CXCL16, IL-1RT2, TNFSF13B/BAFF), T/NK cells (FASLG), leukocytes (ICAM2) and endothelial cells (SELE). ConclusionIn addition to confirming the diagnostic potential of urine ALCAM, CD163, MCP1, SELL, ICAM1, VCAM1, NGAL and TWEAK for active LN, this study adds urine ICAM-2, FABP4, FASLG, IGFBP-2, SELE, and TNFSF13B/BAFF as additional markers that warrant systematic validation in larger cross-sectional and longitudinal cohorts.

Successful treatment of refractory interstitial lung disease with cyclophosphamide and pirfenidone in a new onset of juvenile SLE; a case report

Introduction and importance: Systemic lupus erythematosus is a systemic immune disease, presented with a broad spectrum of clinical manifestations. The occurrence of interstitial lung disease as the initial manifestation of systemic lupus erythematosus is very rare. Case presentation: We present the case of a 6-year-old girl who presented with symptoms of fatigue, fever, oral ulcers, and dry cough with difficulty breathing. On physical examination, the patient had fever and oral ulcers, in addition of acute phase reactant analysis, positive ANA and double stranded DNA. Chest CT images showed nonspecific interstitial pneumonia + organizing pneumonia pattern, leading to the diagnosis of onset of systemic lupus erythematosus with interstitial lung disease. The patient was treated with steroids and azathioprine for one year, and the radiological and immunological resolution was noted. However, the patient continued to cough, have difficulty breathing, and was readmitted to the hospital due to SLE recurrence after 1 year of follow-up. Despite continued corticosteroid therapy and monthly administration of steroids and cyclophosphamide (CYS) for 6 months, the patient’s respiratory symptoms and chest X-ray results did not improve significantly. The patient was then prescribed a daily regimen of cyclophosphamide and pirfenidone, which was found to be effective in reducing the steroid dose and achieving remission after one year of follow-up. Clinical discussion: Treatment of connective tissue disease-associated interstitial lung disease is difficult due to a lack of treatment data. Conclusion: This case provided evidence of the efficacy of combination therapy of pirfenidone and cyclophosphamide for refractory connective tissue disease-associated interstitial lung disease in young children.

Bilateral Parotitis in a Young Male Patient: An Unusual Initial Manifestation of Systemic Lupus Erythematosus

Bilateral Parotitis in a Young Male Patient: An Unusual Initial Manifestation of Systemic Lupus Erythematosus

Thrombosis of the lower right limb in an 11-year-old boy – the first manifestation of systemic lupus erythematosus triggered by SARS-CoV-2 infection

Thrombosis of the lower right limb in an 11-year-old boy – the first manifestation of systemic lupus erythematosus triggered by SARS-CoV-2 infection

Evaluation of Neurological Manifestations of Systemic Lupus Erythematosus

Abstract Background: Neuropsychiatric symptoms are typical consequences in patients with systemic lupus erythematosus (SLE). There is no apparent link between the clinical parameters of SLE patients and the development of neuropsychiatric symptoms. Objectives: to determine the incidence of neurological manifestations and the risks associated with them in SLE patients. Patients and Methods: This is a case-series study comprised 65 patients who visited the rheumatology Department at Baghdad Teaching Hospital/Medical City between January 2022 and February 2023. All patients' demographic and clinical data, including age, gender, disease duration, type and duration of treatment, general signs of the disease, and neurological and psychiatric manifestations of SLE, were collected. Laboratory data comprised plasma anti-phospholipid antibodies (aPL), anti-double stranded DNA (anti-dsDNA), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). The cognitive dysfunction was assessed using the six-item cognitive impairment test (6CIT). Results: Out of 65 patients, 34 (52.3%) were found to have at least one neuropsychiatric SLE (NPSLE) manifestation. Headache and depression were the most common NPSLE manifestation encountered in 36 patients (55.4%) followed by psychosis (21.5%), neuropathy (16.9%) and stroke and seizure (13.5%). In multivariate analysis, each of age &gt;35 years (OR= 2.92, 95%CI= 1.12-34.2, p= 0.10), disease duration &gt;5 years (4.45, 95%CI=1.23-28.43, p= 0.001), anti-phospholipid Abs (OR= 4.22, 95%CI= 1.17-89.38, p= 0.036), lupus nephritis (OR= 6.34, 95%CI= 1.27- 64.98, p= 0.029) and 6CIT&gt;3 (OR= 5.83, 95%CI= 1.55- 21.87, p= 0.009) are independent predictors for NPSLE in patients with SLE. Conclusions: Neuropsychiatric manifestations developed in more than half of the SLE cases studied within up to six-year of disease duration. Headache and depression, psychosis and neuropathy are the most common NPSLE manifestations. Older age and longer disease duration are risk factors for development of NPSLE. Clinically, anti-phospholipid antibodies, lupus nephritis and a high score of the six-item cognitive impairment test (&gt;8) are predictors for NPSLE. Received: May, 2023 Accepted: Sept., 2023 Published: Jan., 2024

Determination of nutrition index and correlation with activity of lupus nephritis

Background/Aim. Lupus nephritis (LN), as an immuno-inflammatory kidney lesion, and the most serious manifestation of systemic lupus erythematosus (SLE), is accompanied by a disorder of the nutritional status of patients. Our goal was to determine the importance of determining and the association of parameters of nutritional status - nutritional risk index (NRI), prognostic nutritional index (PNI) and control nutritional status (CONUT) with standard parameters of LN activity. Methods. The clinical study included a group of 92 subjects. 67 patients had LN (34 patients had LN active disease , the LNa group, and 33 patients were in LN remission, the LNr group) and 25 healthy subjects (control group). In addition to standard laboratory parameters, LN activity parameters, derived parameters were also determined: PNI=10 x albumin value (g/dL) + 0.005 x number of peripheral lymphocytes (/mm3); NRI = 1.519 ? serum albumin, g/dL + 41.7 ? weight (kg)/ideal body weight ( kg); CONUT score = serum albumin + total lymphocyte score + total cholesterol. Results. A statistically significant difference between all three groups was observed for the PNI (p=0.001) and for the CONUT score (p=0.000), while the NRI did not have a significant difference. Statistical significance was found for the correlation of PNI in the LNa group, with the levels of albumin, complement C3 and C4, and a significant negative correlation with the value of anti-ds-DNA Ab. NRI correlated with statistical significance only with proteinuria in the LNa group. CONUT showed significant correlations with the most of the parameters for disease activity: negative correlation with albumin and complement C3 (p = 0.000), and positive correlation with anti -double strand (ds) - DNA Antibody (p=0.002),with Systemic Lupus Erythematosus Disease Activity Index/renal (SLEDAI/r) and with proteinuria/24 hrs (p=0.000). Conclusion. In our group of patients, a statistically significant difference was observed between the groups for the nutrition score CONUT. and the PNI. Their correlation with standard parameters of active disease was significant for most parameters in the group of patients with LNa.

Demographics and clinical manifestations of lupus patients: experience from a private hospital in Saudi Arabia

Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder characterized by a chronic pattern of relapses and remissions, with variable presentations ranging from mild skin manifestations to severe, life-threatening illness. The disease is multisystematic, with the most severe complications related to the kidneys and nervous system. Among the SLE manifestations, lupus nephritis is common, observable in approximately 40% of SLE patients. This study, conducted at a private hospital in Saudi Arabia, aimed to evaluate the demographic characteristics, clinical presentations, and laboratory results of patients with SLE. Methods: This retrospective study involved 105 SLE patients who were seen in the rheumatology clinic at the Specialized Medical Center in Riyadh from 2007 to 2022. The medical records of the patients were reviewed for patient demographics, clinical and serological characteristics, and therapeutic data. Results: The largest proportion (34.3%) was aged between 31 and 40 years. Female dominancy was found, as females represented 91 patients (86.7%). Joint involvement was found to be the most affected organ in the majority of the patients, accounting for 80 patients (76.2%), while the least affected organ was the heart, with cardiac manifestations present in 7 patients (6.7%). Conclusion: The majority of patients (95.2%) displayed a positive antinuclear antibody test, and more than one-half of the patients (68.6%) displayed positive anti-double stranded DNA. The most reported medication was hydroxychloroquine in 104 patients (99%), followed by steroids in 89 patients (84.8%).

Lumbar disc herniation in systemic lupus erythematosus: A case report

The most frequent neurological manifestation in SLE (Systemic Lupus Erythematosus) is cognitive disorder, so lumbar disc herniation in SLE is uncommon. Disc herniation is a degenerative disc disorder (DDD) that is often correlated with aging. However it can caused by an inflammatory reaction. TNF-α (Tumor Necrosis Factor-alpha) is an essential pro-inflammatory cytokine in DDD-related SLE. We present the case of a 26‐year‐old female with SLE and disc herniation L5-S1.

Neurological manifestations in systemic lupus erythematosus: A case with an individualized therapeutic approach

Vasculitis occurs frequently in systemic lupus erythematosus (SLE) patients with an active disease and poor prognosis. Nervous system vasculitis – specifically, multiple mononeuropathy, seizures, and transverse myelitis – is among the most severe complications in SLE that need timely aggressive therapy. Unfortunately, no robust literature is available to guide their management, and therapeutic recommendations are commonly based upon other autoimmune conditions or case reports, case series, and expert opinions. We hereby present a case of a 27-year-old female patient with SLE that sequentially developed an asymmetric distal axonal sensorimotor neuropathy in her limbs and digital ischemic lesions of the hands, that progressed despite maximal treatment with standard therapies, thus requiring several sessions of plasmapheresis.

A case report on systemic lupus erythematosus

The abstract encapsulates the complex landscape of systemic lupus erythematosus (SLE), an autoimmune disease impacting multiple organ systems, characterized by immunosuppression and immunomodulation. SLE is recognized as a quintessential connective tissue disorder arising from immune system dysfunction and an overabundance of diverse autoantibodies. Clinical manifestations of SLE encompass nonspecific constitutional symptoms, including fever, exhaustion, anorexia, weight loss, and arthralgias. Additionally, signs of generalized inflammation like hepatosplenomegaly and lymphadenopathy may manifest at disease onset or during flare-ups. The adaptive immune response in SLE is underpinned by the critical role of B lymphocytes in generating autoantibodies, presenting autoantigens, and activating autoreactive T cells. Treatment strategies for SLE primarily involve biologics and therapeutic options approved by the FDA for refractory cutaneous, articular, and renal disease. Belimumab, infliximab, rituximab, abatacept, and tocilizumab represent some of these approved medications. The management of SLE during remission emphasizes the cautious use of prednisone to mitigate flare-ups, considering potential adverse psychiatric effects associated with steroid medication.[14]

Effects of Acupuncture Therapy at the Mingmen (GV4) and Zusanli (ST36) Points on the Expression of Transforming Growth Factor Beta 1 in Mice with Lupus Nephritis Model

Introduction: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune inflammation involving various factors and autoantibodies targeting cell components, resulting in epigenetic changes. Lupus nephritis is one of the clinical manifestations of SLE. Nowadays, it is known that acupuncture could inhibit disease development, including chronic nephritis, chronic diarrhea, lumbago adnexitis, impotence, enuresis in children, myelitis, and endometritis. Thus, this study aimed to examine the effect of improving Mingmen (GV4) and Zusanli (ST36) point acupuncture therapy on the expression of Transforming Growth Factor Beta 1 (TGFβ1) in lupus nephritis model mice. Method: It was a laboratory experiment on mice (Mus musculus) lupus nephritis model with a post-test only with a control group design. The research samples were divided into four groups, with seven mice in each group, consisting of a control group (KN), a negative control group given pristane (K), treatment group 1 (P1); given pristane and methylprednisolone, and a treatment group 2 (P2); given pristane and acupuncture at the Mingmen (GV4) and Zusanli (ST36) points. This acupuncture needle insertion was carried out thrice a week for 12 insertions during the intervention. The bivariate analysis was done using Kruskal Wallis. Results: There were 28 samples examined in this study. we found that the TGFβ1 expression was high in group P2 (72.86±11.13), after that followed by group P1 (65.71±25.73), N (60.71±25.24), and K (5.88±5.35). According to the bivariate analysis, it showed a significant difference in TGF-β (p= 0.010). Conclusion: Mingmen (GV4) and Zusanli (ST36) point acupuncture therapy improves TGFβ1 expression. Acupuncture therapy triggers inhibition of TGF-β1 expression in lupus nephritis model mice.

Seorang Wanita Usia 23 Tahun Dengan Anemia Mikrositik Hipokromik Suspect Systemic Lupus Erythematosus (SLE)

Systemic Lupus Erythematosus (SLE) is an autoimmune inflammatory disease with diverse clinical manifestations, disease course and prognosis, and it is difficult to predict the onset of acute and subtle manifestations, can attack various organs of the body, and can recur. Hematological manifestations in SLE occur frequently and are one of the criteria for ACR. Thrombocytopenia occurs in 25% - 50% of patients, leukopenia occurs in around 50% and hemolytic anemia with positive Coombs test results in around 10%. Cytopenia that occurs is usually the result of peripheral damage mediated by autoantibodies that cause bone marrow hypercellularity. In rare cases, hypocellularity occurs in the bone marrow due to mediation of T cells that inhibit hemopoetic cells, which causes bone marrow failure and causes anemia gravis. A 23 year old woman came with complaints of paleness, fatigue, decreased appetite, joint pain, nausea, vomiting, headaches, dizzy eyes. On laboratory examination on June 12 2023, microcytic hypochromic anemia was found, on June 13 2023, microcytic hypochromic anemia was found, on peripheral blood morphology examination, anemia was suspected due to iron deficiency, and there was a bacterial and parasitic infection process, on June 15 2023, hypokalemia was found. , hyperchloremia, hypocalcemia. On June 16, 2023, microcytic hypochromic anemia was found. On ECG examination, benign Ves arrhythmia was found. On chest examination, the lung showed no abnormalities, the cast size was normal. On ultrasound examination, Nephrolithiasis Dextra was found. So it was found on physical examination, and the patient's supporting examination was confirmed as microcytic hypochromic anemia suspect systemic lupus erythematosus, however in the patient in this case report it could not be established as systemic lupus erythematosus, because the patient was not willing to be referred to Zainal Abidin General Hospital, Banda Aceh for treatment. further examination.

Managing Lupus Nephritis in Children and Adolescents.

Lupus nephritis is an important manifestation of systemic lupus erythematosus, which leads to chronic kidney disease, kidney failure, and can result in mortality. About 35%-60% of children with systemic lupus erythematosus develop kidney involvement. Over the past few decades, the outcome of patients with lupus nephritis has improved significantly with advances in immunosuppressive therapies and clinical management. Nonetheless, there is a paucity of high-level evidence to guide the management of childhood-onset lupus nephritis, because of the relatively small number of patients at each centre and also because children and adolescents are often excluded from clinical trials. Children and adults differ in more ways than just size, and there are remarkable differences between childhood- and adult-onset lupus nephritis in terms of disease severity, treatment efficacy, tolerance to medications and most importantly, psychosocial perspective. In this article, we review the 'art and science' of managing childhood-onset lupus nephritis, which has evolved in recent years, and highlight special considerations in this specific patient population.

Unveiling the Link Between Antiphospholipid Antibodies and Cognitive Dysfunction in the Almenara Lupus Cohort.

Cognitive dysfunction is a prevalent manifestation of systemic lupus erythematosus (SLE). There is evidence for the role of antiphospholipid (aPL) antibodies on its etiopathogenesis. Our objective was to identify the association between aPL antibodies and cognitive dysfunction in SLE patients. This cross-sectional study included 135 patients evaluated from March 2015 to October 2017 at one center. Cognitive deficit was measured using the NEUROPSI test. Disease activity and damage were ascertained using the SLEDAI-2K (SLE Disease Activity Index 2000) and the SDI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), respectively; aPL antibodies were measured by enzyme-linked immunosorbent assay. The association between cognitive dysfunction and aPL antibodies was evaluated using univariable and multivariable linear regression models adjusted for age, sex, education, socioeconomic status, disease duration, SLEDAI-2K, SDI, mean current dose of prednisone, time of exposure to glucocorticoids, and drug use (immunosuppressants, hydroxychloroquine, aspirin, and warfarin). One hundred thirty-one patients (97.1%) were women; their mean (SD) age was 46.6 (12.5) years; 59 patients (43.7%) had positivity for at least 1 aPL antibody. IgM anticardiolipin (aCL) was positive in 24.5%, IgG in 13.5%, IgM aβ2GP1 in 16.8%, IgG anti-β2 glycoprotein in 24.6%, and the lupus anticoagulant in 5.3%. Ninety patients (66.7%) had some cognitive dysfunction. In the univariable analysis, a significant correlation between the NEUROPSI score and IgM aCL antibodies was found (B = -20.87 [SE, 3.2]; p < 0.001), which remained significant in the multivariable model (B = -13.89 [SE, 3.14]; p < 0.001). IgM aCL antibodies are associated with cognitive dysfunction in patients with SLE. Larger and longitudinal studies are needed to assess the impact of these findings.

Faslpr gene dosage tunes the extent of lymphoproliferation and T cell differentiation in lupus

Sle1 and Faslpr are two lupus susceptibility loci that lead to manifestations of systemic lupus erythematosus. To evaluate the dosage effects of Faslpr in determining cellular and serological phenotypes associated with lupus, we developed a new C57BL/6 (B6) congenic lupus strain, B6.Sle1/Sle1.Faslpr/+ (Sle1homo.lprhet) and compared it with B6.Faslpr/lpr (lprhomo), B6.Sle1/Sle1 (Sle1homo), and B6.Sle1/Sle1.Faslpr/lpr (Sle1homo.lprhomo) strains. Whereas Sle1homo.lprhomo mice exhibited profound lymphoproliferation and early mortality, Sle1homo.lprhet mice had a lifespan comparable to B6 mice, with no evidence of splenomegaly or lymphadenopathy. Compared to B6 monogenic lupus strains, Sle1homo.lprhet mice exhibited significantly elevated serum ANA antibodies and increased proteinuria. Additionally, Sle1homo.lprhet T cells had an increased propensity to differentiate into Th1 cells. Gene dose effects of Faslpr were noted in upregulating serum IL-1⍺, IL-2, and IL-27. Taken together, Sle1homo.lprhet strain is a new C57BL/6-based model of lupus, ideal for genetic studies, autoantibody repertoire investigation, and for exploring Th1 effector cell skewing without early-age lymphoproliferative autoimmunity.