The patient was a girl aged 10 years and 10 months, with weakness, pale complexion, and rash as the initial presentation. She had the manifestations of anemia, thrombocytopenia, hematuria-proteinuria with renal insufficiency, hypocomplementemia, polyserositis, and positive anti-nuclear antibody and anti-dsDNA antibody. The girl was initially diagnosed with systemic lupus erythematosus and lupus nephritis. She demonstrated a suboptimal response to methylprednisolone pulse therapy, intravenous immunoglobulin administration, and therapeutic plasma exchange. She had persistent anemia, thrombocytopenia, abnormal renal function, elevated lactate dehydrogenase, decreased complement factors H and I, increased antibodies to C3 converting enzyme, and normal ADAMTS13 activity. She was diagnosed with complement-mediated hemolytic thrombotic microangiopathy secondary to systemic lupus erythematosus. The patient's condition improved after treatment with two doses of eculizumab (600 mg per dose). Patients with systemic lupus erythematosus complicated by thrombotic microangiopathy often have a severe disease course and poor prognosis; therefore, early recognition and aggressive intervention are crucial for improving outcomes.
Humans ; Female ; Lupus Erythematosus, Systemic/drug therapy* ; Thrombotic Microangiopathies/etiology* ; Antibodies, Monoclonal, Humanized/therapeutic use* ; Child

Overlap syndrome is a rare condition involving the coexistence of at least two distinct autoimmune diseases, such as systemic lupus erythematosus and systemic sclerosis. This condition has limited studies on epidemiology probably because it is often under-recognized. We present a 22-year-old Filipino female with a 10-month history of hyperpigmented patches on the malar surface and extremities, with associated photosensitivity, fatigue, pallor, arthralgia, and oral ulcers, and positive antinuclear antibody titer. She was treated with oral Prednisone in tapering doses, leading to clinical improvement. Eight months later, there was a recurrence of hyperpigmented patches on the face and extremities with skin tightening and diffuse hair loss, development of shiny skin with facial fold loss, a beak-like nasal appearance, and episodes of dyspnea and malaise. Consistent with scleroderma, the patient was started on mycophenolate mofetil (MMF) 500 mg daily, with close monitoring for disease progression and systemic involvement. Overlap syndrome remains under-recognized due to its variable presentation and rarity. Treatment is individualized based on the specific connective tissue diseases involved and the patient’s symptoms. Multidisciplinary care is crucial for timely management and to adjust treatment as needed, given the potential for life-threatening complications involving cutaneous and internal organs.

Systemic Lupus erythematosus (SLE) is a multiorgan autoimmune disease that affects 20-150 per 100,000 women. It is a mutagenic disease which causes formation of autoantibodies immune complexes that leads to inflammation in different organs leading to organ damage. We present a case of a young female who was newly diagnosed to have SLE. She presented with an elevated ANA, low C3 and elevated Anti-DS DNA. She first manifested with epistaxis and subsequently experienced the various complications of SLE such as infection, thrombosis, bleeding, ascites, etc. The initial presentation of normochromic, normocytic anemia and thrombocytopenia together with further work-ups supported another concomitant autoimmune disease, namely Evan’s syndrome. Evan’s syndrome is a rare manifestation of SLE, and is observed in only 2.73% of the population. In addition, the patient manifested with sudden onset of right-sided body weakness with Cranial CT scan findings of areas of focal infarction in the frontal lobe with concomitant acute intracranial hemorrhages. The evidence of both thrombosis and hemorrhage provided conflicting management strategies for this patient. The use of hydroxychloroquine, which is the cornerstone of lupus therapy, provided beneficial antithrombotic effects. A multidisciplinary approach to management and prudent choice of medications were vital in the success of treatment on such a complicated case.

Systemic lupus erythematosus (SLE) is the most common form of lupus and a chronic autoimmune disorder that can affect multiple organ systems including the joints, skin, the cardiovascular system and even the central and peripheral nervous system. Although rare, these patients may present with neuropsychiatric symptoms. This patient presented initially with an SLE flare associated with sudden focal to generalized tonic-clonic seizures. Further rheumatologic workup was done which revealed that the patient also has scleroderma, an autoimmune connective tissue that causes inflammation of the skin and other key internal organs. Due to the seizure occurrence, cranial magnetic resonance imaging (MRI) was done which showed incidental mesial temporal sclerosis, which is the scarring of the medial part of the said lobe of the brain. Her overlap syndrome was managed with Hydrocortisone and she was given Valproic acid as her anti-epileptic drug with no recurrence of seizure afterwards.

INTRODUCTION: Hydroxychloroquine (HCQ), originally an antimalarial drug, is currently used to treat multiple disorders, especially rheumatic diseases. Given its good efficacy and safety, HCQ is widely administered in pregnant patients. However, the safety profile of HCQ during pregnancy remains controversial due to limited research. In addition, HCQ has been reported to reduce preeclampsia in patients with systemic lupus erythematosus (SLE) and could potentially alleviate the symptom of preeclampsia. However, the clinical profile and molecular mechanism of HCQ in preeclampsia is yet to be fully understood. METHOD: We reviewed the literature on HCQ treatment in pregnancy with rheumatic diseases and preeclamp-sia in PubMed and Web of Science. We also discussed the safety of long-term therapy with HCQ during pregnancy. RESULTS: HCQ mainly modulates autoimmune response through inhibition of lysosomal function, toll-like receptor (TLR) signalling, nicotinamide adenine dinucleotide phosphate-mediated oxidative stress and autophagy. Benefits of HCQ in treating rheumatic diseases, including antiphospholipid syndrome, rheumatoid arthritis and Sjogren's syndrome during pregnancy, has been demonstrated in clinics. In particular, multiple clinical guidelines recommend HCQ as an indispensable therapeutic drug for pregnant patients with SLE. Additionally, it may potentially function in preeclampsia to improve clinical symptoms. CONCLUSION HCQ is effectively used for rheumatic diseases during pregnancy. The benefits of HCQ treatment in rheumatic diseases outweigh the risk of adverse reactions it induces in pregnant women.
Humans ; Hydroxychloroquine/pharmacology* ; Pregnancy ; Female ; Antirheumatic Agents/pharmacology* ; Rheumatic Diseases/drug therapy* ; Pregnancy Complications/drug therapy* ; Pre-Eclampsia/prevention & control* ; Lupus Erythematosus, Systemic/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Antiphospholipid Syndrome/drug therapy* ; Sjogren's Syndrome/drug therapy*

The remarkable efficacy of chimeric antigen receptor (CAR) T cell therapy in hematological malignancies has provided a solid basis for the therapeutic concept, wherein specific pathogenic cell populations can be eradicated by means of targeted recognition. During the past few years, CAR-based cell therapies have been extensively investigated in preclinical and clinical research across various non-tumor diseases, with particular emphasis in the treatment of autoimmune diseases (ADs), yielding significant advancements. The recent deployment of CD19-directed CAR T cells has induced long-lasting, drug-free remission in patients with systemic lupus erythematosus (SLE) and other systemic ADs, alongside a more profound immune reconstruction of B cell repertoire compared with conventional immunosuppressive agents and B cell-targeting biologics. Despite the initial success achieved by CAR T cell therapy, it is critical to acknowledge the divergences in its application between cancer and ADs. Through examining recent clinical studies and ongoing research, we highlight the transformative potential of this therapeutic approach in the treatment of SLE, while also addressing the challenges and future directions necessary to enhance the long-term efficacy and safety of CAR-based cell therapies in clinical practice.
Humans ; Lupus Erythematosus, Systemic/immunology* ; Receptors, Chimeric Antigen/metabolism* ; Immunotherapy, Adoptive/methods* ; Cell- and Tissue-Based Therapy/methods* ; Animals ; T-Lymphocytes/immunology*

Systemic lupus erythematosus (SLE) is an autoimmune disease accompanied by various complications, and the exact etiology remains unclear. Treatments for SLE encompass hormone therapy, plasma exchange and immunoadsorption, and targeted biological therapies. Berbamine (BBM), a cellular immunopotentiator with diverse biological functions, has not been reported to have immunomodulatory and therapeutic effects on SLE. The mice were divided into control group, model group, positive control group, low, medium and high BBM groups. In control group, C57BL/6J wild mice received intraperitoneal injection of saline. In model group, MRL/lpr lupus mice were treated with intraperitoneal injection of saline. In positive control group, MRL/lpr lupus mice received intragastric administration of hydroxychloroquine sulfate tablets [Plaquenil, 150 mg/(kg·d)]. In BBM groups, MRL/lpr lupus mice received intragastric administration of different concentration of BBM respectively [20 mg/(kg·d), 50 mg/(kg·d), 100 mg/(kg·d)]. After 8 weeks of treatment, blood was collected from the retro-orbital venous plexus, and ELISA was used to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, antinuclear antibodies (ANA), and anti-small nuclear ribonucleoprotein/Sm (snRNP/Sm) antibodies. Spleen tissues were collected for analysis of Th1/Th2 ratio by flow cytometry. The RNA and protein of spleen were extracted, and the levels of T-box transcription factor T-bet and GATA3 (GATA binding protein 3) mRNA and protein were detected by qRT-PCR and Western blot. The proliferation of white blood cells in the blood was tested by blood routine test. The histopathological changes of kidneys of each group were detected by HE staining. Compared with the model group, the levels of ANA, anti-dsDNA, and anti-snRNP/Sm antibodies were significantly reduced in the BBM-treated groups. The Th1/Th2 ratio was significantly decreased in the model group, but reversed by BBM. Compared with the control group, T-bet expression was significantly downregulated, while GATA3 expression was significantly upregulated in the model group. After BBM intervention, T-bet expression significantly increased, while GATA3 expression decreased compared with the model group. The number of white blood cells significantly decreased in the model group, and increased in the BBM-treated groups. In the model group, the glomerular mesangial and endothelial cells showed significant hyperplasia, clear thrombus was observed in the dilated capillaries, and inflammatory cells infiltrated in the renal interstitium. In medium and high BBM groups, the infiltration of inflammatory cells and capillary thrombosis were significantly decreased. In conclusion, BBM exhibits certain immunomodulatory effects on SLE and promotes the proliferation of white blood cells.
Animals ; Lupus Erythematosus, Systemic/immunology* ; Mice ; Mice, Inbred C57BL ; Mice, Inbred MRL lpr ; Female ; Benzylisoquinolines/pharmacology*

Objective To investigate the common molecular features of immunothrombosis, thus enhancing the comprehension of thrombosis triggered by immune and inflammatory responses and offering crucial insights for identifying potential diagnostic and therapeutic targets. Methods Differential gene expression analysis and functional enrichment analysis were conducted on datasets of systemic lupus erythematosus (SLE) and venous thromboembolism (VTE). The intersection of differentially expressed genes in SLE and VTE with those of neutrophil extracellular traps (NET) yielded cross-talk genes (CG) for SLE-NET and VTE-NET interaction. Further analysis included functional enrichment and protein-protein interaction (PPI) network assessments of these CG to identify hub genes. Venn diagrams and receiver operating characteristic (ROC) curve analysis were employed to pinpoint the most effective shared diagnostic CG, which were validated using a graft-versus-host disease (GVHD) dataset. Results Differential expression genes in SLE and VTE were associated with distinct biological processes, whereas SLE-NET-CG and VTE-NET-CG were implicated in pathways related to leukocyte migration, inflammatory response, and immune response. Through PPI network analysis, several hub genes were identified, with matrix metalloproteinase 9 (MMP9) and S100 calcium-binding protein A12 (S100A12) emerging as the best shared diagnostic CG for SLE (AUC: 0.936 and 0.832) and VTE (AUC: 0.719 and 0.759). Notably, MMP9 exhibited good diagnostic performance in the GVHD dataset (AUC: 0.696). Conclusion This study unveils the common molecular features of SLE, VTE, and NET, emphasizing MMP9 and S100A12 as the optimal shared diagnostic CG, thus providing valuable evidence for the diagnosis and therapeutic strategies related to immunothrombosis. Additionally, the expression of MMP9 in GVHD highlights its critical role in the risk of VTE associated with immune system disorders.
Humans ; Computational Biology/methods* ; Lupus Erythematosus, Systemic/immunology* ; Protein Interaction Maps/genetics* ; Venous Thromboembolism/therapy* ; Matrix Metalloproteinase 9/genetics* ; Extracellular Traps/metabolism* ; Gene Regulatory Networks ; Thrombosis/immunology* ; Graft vs Host Disease/genetics* ; Gene Expression Profiling

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with diverse clinical symptoms, which involves multiple systems and organs such as the kidney, cardiovascular system, and nervous system. The main characteristic of SLE is the mistaken attacks on self-tissues by the immune system, but the specific pathogenesis is still unclear. This paper reviews and compares the modeling mechanisms and main pathological manifestations of spontaneous and experimental mouse models of SLE, which can provide evidences for selecting appropriate mouse models in studies on the pathogenesis, clinical diagnosis and treatment of SLE.
Animals ; Lupus Erythematosus, Systemic/immunology* ; Disease Models, Animal ; Mice ; Humans

Objective To explore the effects of S100 calcium-binding protein A9 (S100A9) gene knockout on the phenotype of systemic lupus erythematosus (SLE) in mice and to clarify the role of S100A9 in the pathogenesis of SLE. Methods Ten female C57BL/6 wild-type and S100A9 knockout (S100A9-KO ) mice were selected, with five wild-type and five S100A9-KO B6 mice receiving imiquimod (IMQ) cream to establish SLE mouse model. The other five wild-type and five S100A9-KO B6 mice were treated as control groups by wiping the skin of the right ear with a cotton swab. After 8 weeks, the mice were sacrificed. The serum was collected from each mouse to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, immunoglobulin G (IgG), B cell activating factor (BAFF), and interleukin 6 (IL-6) using ELISA. The levels of serum creatinine were determined using a sarcosine oxidase method. Urine was collected to measure urinary protein concentration. Kidneys were collected and stained with hematoxylin and eosin (H&E) for evaluating histological changes. Results After IMQ treatment, the length and weight of spleen, levels of serum creatinine, anti-dsDNA antibodies, IgG, BAFF, IL-6, and urinary protein in the IMQ B6 group and IMQ S100A9-KO B6 group were significantly higher than those of the control groups. Lupus-like changes including increased glomerular volume and tubular epithelial swelling were observed in kidneys from the IMQ and IMQ S100A9-KO groups. However, compared with the IMQ B6 group, the IMQ S100A9-KO B6 group exhibited milder levels of serum and urine indicators as well as the lupus-like symptoms. Conclusion IMQ could induce lupus-like symptoms in both wild-type B6 mice and S100A9-KO B6 mice, but the lesions in S100A9 knockout mice are milder. Theses results suggested that S100A9 is involved in and promotes the pathogenesis of SLE.
Animals ; Lupus Erythematosus, Systemic/chemically induced* ; Female ; Calgranulin B/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Phenotype ; Mice ; Interleukin-6/blood* ; Disease Models, Animal ; Antibodies, Antinuclear/blood* ; B-Cell Activating Factor/blood* ; Immunoglobulin G/blood* ; Kidney/pathology*