Advances in Targeted Therapy for Systemic Lupus Erythematosus: Current Treatments and Novel Approaches

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 929 - 929

Published: Jan. 23, 2025

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse clinical manifestations that can lead to severe organ damage. The complex pathophysiology of SLE makes treatment selection difficult. This review examines the current evidence for biological therapies in SLE, including anti-B cell activating factor antibody belimumab; type I interferon receptor antagonist anifrolumab; novel calcineurin inhibitor voclosporin; and rituximab, which targets CD20 on B cells. We also describe emerging therapies, agents development CD19-directed chimeric antigen (CAR) T therapy, has shown promise early experience. Recent advances biomarker research, signatures transcriptomic profiles, may facilitate patient stratification selection. offers insights into future strategies patients by analyzing trial results recent immunological findings.

Language: Английский

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Lymphatic messengers: Non-antigen soluble mediators from diseased tissues to draining lymph nodes

Current Opinion in Immunology, Journal Year: 2025, Volume and Issue: 93, P. 102536 - 102536

Published: Feb. 5, 2025

Language: Английский

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Cell type-specific regulation of the pentose phoshate pathway during development and metabolic stress-driven autoimmune diseases: Relevance for inflammatory liver, renal, endocrine, cardiovascular and neurobehavioral comorbidites, carcinogenesis, and aging

Autoimmunity Reviews, Journal Year: 2025, Volume and Issue: 24(5), P. 103781 - 103781

Published: Feb. 24, 2025

Language: Английский

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Across ancestries, HLA-B*08:01∼DRB1*03:01 (DR3) and HLA-DQA*01:02 (DR2) increase the risk to develop juvenile-onset systemic lupus erythematosus through low complement C4 levels

Journal of Translational Autoimmunity, Journal Year: 2025, Volume and Issue: 10, P. 100268 - 100268

Published: Jan. 7, 2025

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease with strong genetic component. Genetic burden higher in children when compared to patients adult-onset SLE, contributing earlier expression and more severe phenotypes. The human leukocyte antigen (HLA) cluster on chromosome 6p21.3 among the most variable genomic regions, representing major risk-factor for SLE adults. Its impact juvenile-onset (j)SLE remains largely unstudied. High-resolution sequencing of HLA class I (A, B, C), II (DRB1, DQA1, DQB1) III (complement C2) was undertaken multi-ancestral UK JSLE Cohort including participants Caucasian (n = 151, 48.8 %), Asian 108, 35.0 %) African/Caribbean 50, 16.2 descent. Considering ancestral variation, clinical associations were tested at level alleles (2-field resolution), associated protein sequences (antigen binding domains, 4-field extended haplotypes (DRh). Although important recombination reported HLA-DR2 -DR3 haplotypes, risk jSLE conserved related (DR2h: DRB1∗15:01, DQA∗01:02, DQB1∗06:02; DR3h: C∗07:02 [Asian], B∗08:01, C2 rs9332730 DRB1∗03:01). HLA-DR7 (DRB1∗07:01, OR 0.44, 95 % CI:0.27-0.72, p 0.0004; DQA1∗02:01, 0.34, CI:0.21-0.56, 1.8 × 10-6) protect Asians from development. Among 23 variables recorded, main association found between low levels complement C4 carriers HLA-DR3h. This not case due HLA-C∗07:02 integration minor allele. Low serum HLA-DQA1∗01:02 (DR2h) Caucasians after excluding HLA-DR3h analysis. An white blood cell counts HLA-A∗03:01P observed across ancestries. variation associates organ domain involvement (hematological) jSLE. Lupus-associated vary groups, underscoring importance approaches studies other diseases.

Language: Английский

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Immune cell alterations in a pristane‐induced lupus model in C57BL/6J mice

Rheumatology & autoimmunity, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 21, 2025

Abstract Background Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by immune‐mediated inflammation affecting multiple organs and systems. The aim of this study was to establish validate a pristane‐induced SLE model in C57BL/6J mice analyze immune cell alterations. Methods Six‐week‐old female were randomly assigned two groups ( n = 6 per group). pristane group received single 0.5 mL intraperitoneal injection pristane, whereas the control saline. Urine samples collected before at 2, 4, months after monitor urinary protein levels. Six postinjection, euthanized, serum, kidney, spleen tissues collected. Serum antinuclear antibody (ANA), double‐stranded DNA(dsDNA), inflammatory cytokine levels (interleukin [IL]‐1β, IL‐6, tumor necrosis factor‐α) quantified enzyme‐linked immunosorbent assay. Histological alterations kidney assessed using hematoxylin eosin, periodic acid‐Schiff, Masson, silver staining, addition direct immunofluorescence for immunoglobulin G complement component 3. Flow cytometry used assess spleen. Results Following exhibited gradual increase size, body weight, ANA, dsDNA, cytokines elevated varying degrees p < 0.05). analysis sections revealed characteristic nephritic alterations, including glomerular swelling lymphocyte infiltration. In spleen, T numbers decreased, proportion myeloid cells significantly increased, particularly monocytes, neutrophils, macrophages Conclusion Pristane successfully induced mice, injury significant populations.

Language: Английский

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The added value of coupling anti-dsDNA and anti-chromatin antibodies in follow-up monitoring of systemic lupus erythematosus patients

Journal of Translational Autoimmunity, Journal Year: 2025, Volume and Issue: 10, P. 100274 - 100274

Published: Jan. 22, 2025

Language: Английский

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Primary cutaneous Mycobacteria avium complex infection in a systemic lupus erythematosus patient: A case report and review

Medicine, Journal Year: 2025, Volume and Issue: 104(6), P. e41450 - e41450

Published: Feb. 7, 2025

Rationale: Nontuberculous mycobacteria infection is becoming more and common in clinical practice, while skin soft tissue an important part. The evaluation of the immune status patients has certain reference value for diagnosis treatment. Patient concerns: A 48-year-old woman developed erythematosus nodule with purulent discharge on right hip 4 months. She had a history systemic lupus than 20 years, stable control prednisone 10 mg/d, azathioprine 50 mg/12 h, hydroxychloroquine 200 h. There was no trauma prior to lesion. Diagnoses: After excluding other sites involved, patient diagnosed as Mycobacterium avium primary cutaneous based laboratory culture, biopsy, sequencing techniques. Interventions: surgical resection, combination oral azithromycin, rifampicin, ethambutol hydrochloride given. Outcomes: lesion healed after months relapse. Lessons: Primary nontuberculous should raise attention immunocompromised even immunocompetent populations.

Language: Английский

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CD38 deficiency leads to a defective short-lived transcriptomic response to chronic graft-versus-host disease induction, involving purinergic signaling-related genes and distinct transcriptomic signatures associated with lupus

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 10, 2025

This study aimed to elucidate the transcriptomic signatures and dysregulated pathways associated with autoimmune response in Cd38 -/- mice compared wild-type (WT) within bm12 chronic graft-versus-host disease (cGVHD) lupus model. We conducted bulk RNA sequencing on peritoneal exudate cells (PECs) spleen (SPC) at two four weeks following adoptive cell transfer. also analyzed from healthy, untreated mice. These analyses revealed a sustained upregulation of transcriptional profile purinergic receptors ectonucleotidases cGVHD WT PECs, which displayed coordinated expression several type I interferon-stimulated genes (ISGs) key molecules involved cyclic GMP-AMP synthase-stimulator interferon (cGAS-STING) signaling pathway, hallmarks pathology. A second receptor profile, included P2rx7 P2rx4 , showed gene components NLRP3 inflammasome its potential activators. processes were transcriptionally less active PECs than PECs. have shown evidence distinct enrichment that define such as Ca 2+ ion homeostasis, division, phagosome, autophagy, senescence, cytokine/cytokine interactions, Th17 Th1/Th2 differentiation versus samples, reflected milder inflammatory elicited relative counterparts allogeneic challenge. Last, we an intense metabolic reprogramming toward oxidative phosphorylation SPC mice, may reflect increased cellular demand for oxygen consumption, contrast short-lived effect level. Overall, these findings support pro-inflammatory immunomodulatory role CD38 during development cGVHD-lupus disease.

Language: Английский

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Cellular and molecular determinants mediating the dysregulated germinal center immune dynamics in systemic lupus erythematosus

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 13, 2025

Systemic lupus erythematosus (SLE) is characterized by dysregulated humoral immunity, leading to the generation of autoreactive B cells that can differentiate both within and outside lymph node (LN) follicles. Here, we employed spatial transcriptomics multiplex imaging investigate follicular immune landscaping in situ transcriptomic profile LNs from SLE individuals. Our analysis revealed robust type I IFN plasma cell signatures compared reactive, control Cell deconvolution T subsets are mainly affected fingerprint Dysregulation TFH differentiation was documented i) significant reduction Bcl6hi cells, ii) reduced density potential IL-4 producing associated with impaired signature signaling iii) loss their correlation GC-B cells. This accompanied a marked an enrichment extrafollicular CD19hiCD11chiTbethi, age-associated (ABCs), known for potential. The increased prevalence IL-21hi further reveals hyperactive microenvironment control. Taken together, our findings highlight altered immunological landscape follicles, likely fueled potent inflammatory signals such as sustained and/or IL-21 signaling. work provides novel insights into molecular cellular dynamics, points druggable targets restore tolerance enhance vaccine responses patients.

Language: Английский

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Just Autoimmunity? The Role of the Innate Immune Response in Lupus

JCR Journal of Clinical Rheumatology, Journal Year: 2025, Volume and Issue: 31(2), P. 71 - 77

Published: Feb. 19, 2025

Abstract Systemic lupus erythematosus is considered a prototype of human autoimmune disease based on the appearance multiple autoantibodies, some which can have direct pathogenic effect tissues. Most therapeutic modalities aim to check enhanced humoral responses by targeting T and B cells with conventional or biologic drugs. However, in cases, clinical response limited frequently takes high toll toxicity patients. The last 2 decades brought up novel discoveries showing profound disturbances innate immune cell function systemic erythematosus, including dysregulated NETosis, increased apoptosis, type 1 interferon, granulopoiesis signatures that are grounded basic biology abnormalities, excessive oxidative stress, mitochondrial dysfunction, upregulation cGAS-STING pathway. Whether prominent autoimmunity component patients sufficient drive this chronic follows breakdown homeostasis environmental factors triggering subject revision.

Language: Английский

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