Search Results (1,080)

Neuroinflammation is increasingly recognized as a key modulator of therapeutic response and adverse events in Alzheimer’s disease (AD), especially during anti-amyloid-β (Aβ) monoclonal antibody (Aβ-mAb) treatment. We applied longitudinal translocator protein (TSPO) positron emission tomography (PET) to evaluate TSPO-associated neuroinflammatory responses to chronic Aβ-mAb therapy and their modulation by the peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone. App^NL-G-F knock-in mice underwent TSPO-PET and Aβ-PET imaging at 5, 7.5, and 10 months of age across four treatment arms: placebo, Aβ-mAb, pioglitazone, and combination therapy. TSPO-PET detected early and progressive neuroinflammatory responses to Aβ-mAb that appeared lower with pioglitazone co-treatment. Both mono- and combination therapy were associated with altered temporal and spatial dynamics of the TSPO-PET signal. In addition, we applied a previously validated microglia desynchronization index based on TSPO-PET connectivity, which captured individual variation in regional TSPO-PET organization and correlated with cognitive performance. Together, TSPO-PET and its regional synchronicity can quantify longitudinal, region-specific treatment effects, which may help differentiate harmful from adaptive neuroinflammatory responses. These findings highlight the potential of TSPO-PET as a stratification biomarker to optimize therapeutic interventions. TSPO-PET therefore enables in vivo tracking of treatment-associated neuroinflammatory responses during anti-Aβ immunotherapy and provides a non-invasive framework for evaluating combination strategies targeting amyloid pathology and immune regulation in AD. Full article

Protein molecularly imprinted polymers (MIPs), as artificial antibodies, are promising for protein separation due to their low cost, easy preparation, and high stability, but their performance is limited by poor mass transfer, imprecise imprinting, and single interaction modes. Herein, dendritic mesoporous silica nanoparticles (DMSNs) were used as the support, and a self-designed multifunctional poly(ionic liquid) macromonomer (p(VIMCD-co-VAIM-co-VSIM-co-VVIM)) served as the functional monomer to achieve directional anchoring of cytochrome C (Cyt-C). Surface-imprinted microspheres (DMSNs@MPS@PILs-MIPs) were prepared via free-radical copolymerization for Cyt-C recognition. The DMSNs possessed interconnected mesoporous channels, good dispersibility, an average particle size of ~80 nm, and a specific surface area of 267.97 m²/g. Ionic liquid monomers were synthesized via alkylation, and the macromonomer was constructed through a two-step method. Molecular dynamics simulations and spectroscopic characterization revealed the macromonomer-stabilized Cyt-C conformation, with interactions dominated by van der Waals forces. The DMSNs@MPS@PILs-MIPs featured a thin imprinted layer (~5 nm) to reduce mass-transfer resistance. Adsorption studies showed Cyt-C adsorption followed Langmuir and pseudo-second-order models, with a maximum capacity of 383.14 mg/g and an imprinting factor of 2.17. Only 12% capacity loss occurred after repeated cycles, indicating robust regeneration stability. This study provides a feasible strategy for constructing protein surface-imprinted polymers based on multifunctional synergistic interactions and conformational stabilization. Full article

Background/Objectives: CTLA-4 is a key checkpoint of peripheral immune regulation, yet its biology cannot be reduced to inhibitory signaling alone. This review discusses CTLA-4 as a dynamic regulatory pathway shaped by ligand handling, intracellular trafficking, recycling, and cell-type-specific function, and examines how these features link molecular mechanism to human disease and therapy. Methods: We synthesized the structural, mechanistic, translational, and clinical literature spanning CTLA-4 molecular biology, cell-type-specific function, inborn errors of immunity, polygenic autoimmunity, transplantation, cancer immunotherapy, and immune-related adverse events. Results: CTLA-4 function depends on surface availability, trans-endocytosis of CD80/CD86, and tight control of endosomal trafficking. These features help explain why CTLA-4 haploinsufficiency, LRBA deficiency, and DEF6 deficiency converge clinically despite different upstream lesions, and why subtler CTLA-4 variation contributes to polygenic autoimmunity. Therapeutic studies also provide mechanistic insight. Abatacept can partly replace pathway function in monogenic disease, whereas belatacept highlights the limits of ligand blockade when endogenous coinhibition is also lost. In oncology, anti-CTLA-4 antibodies act through a more complex interplay involving checkpoint blockade, Fc biology, intratumoral Treg depletion, and receptor recycling. Emerging next-generation agents aim to retain antitumor activity while reducing systemic toxicity through more selective use of these mechanisms. Conclusions: Rather than a static inhibitory receptor, CTLA-4 is better viewed as a context-dependent regulatory pathway whose function depends on trafficking, surface availability, and cellular context. This perspective links molecular mechanism to clinical phenotype and supports more precise CTLA-4-targeted therapy. Full article

Respiratory syncytial virus (RSV) remains a leading cause of severe lower respiratory tract disease in infants, older adults, and immunocompromised individuals. Over the past decade, advances in structural biology, particularly cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), have transformed our understanding of RSV architecture, dynamics, and the mechanisms of entry and replication. High-resolution structures of the prefusion F glycoprotein (pre-F) and its complexes with neutralizing antibodies established the rationale for structure-guided antigen stabilization and directly enabled the development of the first licensed RSV vaccines. Complementary structures of the ribonucleoprotein, polymerase complex, and matrix lattice have broadened therapeutic targets beyond F. Here, we summarize these structural advances; review current structure-guided vaccine, antibody, and antiviral development efforts; and highlight priorities for next-generation vaccines and therapeutics. Full article

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease, with anti-double-stranded DNA (anti-dsDNA) antibodies as its serological biomarkers. However, conventional anti-dsDNA antibody detection methods, which mainly rely on antibody-binding assays, often suffer from limited sensitivity and specificity, cumbersome procedures, and poor suitability for accurate clinical analysis. Herein, we developed an integrated detection system combining a circularly permuted fluorescent protein (cpFP)-based biosensor with a microfluidic chip for rapid and reliable anti-dsDNA antibody detection. The biosensor, cpR-dsAb-C1, was engineered from mApple by inserting an affinity peptide identified through phage display, enabling specific recognition of the variable region of anti-dsDNA antibodies. The biosensor exhibited good sensitivity, specificity, and anti-interference capability. Furthermore, integration of cpR-dsAb-C1 with a polydimethylsiloxane (PDMS)-based microfluidic chip yielded a microfluidic detection platform with good linearity for rapid antibody analysis. Clinical validation showed significantly higher anti-dsDNA antibody levels in patients with SLE than in healthy controls, and the results were consistent with those obtained using routine clinical methods, with an accuracy exceeding 95%. Overall, this system provides a promising low-cost, efficient, and accurate strategy for the early diagnosis and dynamic monitoring of SLE. Full article

Talaromyces marneffei is a dimorphic fungal pathogen that can subvert host immune defenses; however, the molecular mechanisms underlying its interactions with host cells remain incompletely understood. Glutathione peroxidase from T. marneffei (TmGpx1) has previously been identified as an antigenic protein that elicits antibody responses in patients with talaromycosis. To elucidate the contribution of TmGpx1 during human–fungal pathogen interaction, the yeast two-hybrid system was performed using TmGpx1 as bait to screen a cDNA library derived from non-induced human macrophage cells. Sixteen candidate host protein partners were identified, with Gene Ontology analysis revealing their predominant association with cytoskeletal and extracellular exosome components. To examine the atomic-level structural interface and dynamic behavior of protein–protein interactions, we employed molecular dynamics (MD) simulations to investigate the interaction between TmGpx1 and FKBP15, a human protein involved in early endosomal regulation and associated with both microtubule and actin filaments. Per-residue decomposition analysis using gmx_MMPBSA identified LEU124 of TmGpx1 and ARG616 of FKBP15 as critical residues mediating the protein–protein interaction. Notably, the key residues of TmGpx1 are located toward the N-terminus and are mapped outside of the catalytic active site, suggesting that the interaction of TmGpx1 with host cytoskeletal components may occur independently of its enzymatic antioxidant activity. Overall, our findings provide novel insights into the repertoire of host cytoskeletal and membrane trafficking proteins that may be targeted for remodeling during T. marneffei infection. Elucidation of these molecular interactions advances our understanding of host–pathogen dynamics and opens new avenues for the development of targeted diagnostics and therapeutic strategies against talaromycosis. Full article

The evaluation of therapeutic response is essential in disease monitoring both for disease status and treatment efficacy in inflammatory bowel disease. Here, we focused on the use of positron emission tomography directed towards granzyme B, a serine protease released by activated cytotoxic T cells and natural killer cells, to evaluate the dynamics of therapeutic response in a colitis model. The goal was to explore the use of granzyme B positron emission tomography as a non-invasive biomarker to monitor disease activity and therapeutic response across several treatments in a dextran sulfate sodium-induced colitis model. C57BL/6 interleukin-10 knockout mice were divided into five groups, including a negative control, positive control and three treatment arms (antitumor necrosis factor, prednisolone, and anti-interleukin-23). The negative control group received regular water, while all other groups were induced with colitis via 3% DSS water for 1 week followed by normal water. Treatments were initiated after colitis was induced (anti-TNF antibody, prednisolone, or anti-IL-23 antibody). Positron emission tomography/computed tomography imaging with 68Ga-NOTA-GZP was performed at baseline (after colitis induction, before therapy), and at 1 and 2 weeks after treatment initiation. Histological analyses were also performed at 1 and 2 weeks after treatment initiation. Gzmb expression and histological changes were also assessed with immunofluorescence staining and bulk ribonucleic acid sequencing. Gzmb-targeted PET imaging revealed distinct longitudinal patterns of colonic tracer uptake related to treatment response. In positive control mice with DSS colitis (no treatment), bowel uptake of ⁶⁸Ga-NOTA-GZP increased significantly from baseline to week 2. Anti-TNF treatment reduced granzyme B positron emission tomography uptake significantly at week 2, approaching levels seen in negative controls. In prednisolone-treated mice, ⁶⁸Ga-NOTA-GZP uptake decreased at week 1 but rose significantly by week 2 but still was in normal range. Anti-IL-23 therapy produced a significantly elevated Gzmb PET signal at week 1, followed by a significant decline by week 2 of treatment. The imaging trends were corroborated by tissue analyses and IF staining for Gzmb, which revealed no colonic expression in negative controls and strong Gzmb elevation in positive controls and the prednisolone group but a decreased Gzmb signal in the anti-TNF and late anti-IL-23 groups. Bulk RNA sequencing also supported these findings, with Gzmb gene expression tracking with inflammation severity and NK/T cell abundance and decreasing after effective therapy. Gzmb-targeted PET/CT allows for dynamic and non-invasive assessment of intestinal immune compartment activity and an assessment of therapy in colitis. Gzmb PET was able to detect initial treatment responses of anti-TNF, steroid and anti-IL-23 based on changes in the Gzmb PET signal. This suggests that clinical Gzmb PET imaging may serve as precision imaging for monitoring disease activity with treatment in IBD and help improve patient care by identifying responders and non-responders in real time. Full article

Functional antibody-dependent enhancement (ADE) represents a fundamental and context-dependent characteristic of antiviral antibody responses, reflecting the dual capacity of antibodies to mediate both the neutralization and Fc receptor-dependent enhancement of infection. In flavivirus research, this duality complicates the interpretation of conventional serological metrics and limits the reliability of single-parameter correlates of immunity, particularly in populations with complex exposure histories. Over the past decade, functional ADE assays have evolved from specialized mechanistic tools into integrated immune assessment platforms supporting translational immunology, vaccine evaluation, and population-level immune surveillance. These platforms incorporate Fcγ receptor-relevant target cell systems, standardized viral inputs, dilution series-based profiling, quantitative enhancement metrics, and structured quality control frameworks to enable reproducible, comparable, and context-aware functional measurements across cohorts and laboratories. A central concept emerging from these developments is that ADE reflects a dynamic functional immune state rather than an intrinsic property of antibodies or a direct indicator of pathological risk. Accordingly, functional ADE platforms support the contextual interpretation of antibody activity across physiologically relevant conditions, facilitating discrimination between transient functional enhancement and clinically meaningful immunological risk. By integrating functional ADE metrics with serological, cellular, and epidemiological data, these platforms provide a structured framework for interpreting immune profiles in vaccine evaluation, booster strategy design, and population-level risk stratification. This review synthesizes the development, standardization, and global dissemination of functional ADE platforms and discusses key principles governing biological relevance, analytical robustness, and inter-site transferability. Emerging directions integrating functional ADE profiling with systems immunology, immunogenomics, and computational modeling are highlighted as pathways toward predictive, decision-support-oriented frameworks. By positioning ADE platforms as immune assessment infrastructures rather than isolated assays, this review underscores their value for mechanistic inquiry, translational interpretation, and preparedness-oriented responses to emerging viral threats in the absence of definitive correlates of protection. Full article

Biomarker detection demands low cost, rapid turnaround, interference resistance, and wide dynamic range. However, traditional immunoassays and nucleic acid amplification methods remain constrained by complex matrices, batch stability, and portability limitations. Molecularly imprinted polymers (MIPs) exhibit “artificial antibody”-like specific recognition and high stability, while nanomaterials (NMs), depending on their composition, structure, and interfacial organization, can provide conductive pathways, catalytic activity, high-density loading sites, or mass-transfer-favorable architectures. Electrochemical biosensors synergistically constructed from these two components achieve complementary functions in recognition, mass transfer, and signal transduction. This paper systematically reviews key strategies and mechanisms for NM–MIP synergistic construction, focusing on six synergistic strategies that target key bottlenecks in mass transfer, signal generation, and interfacial stability: dynamic response regulation, hierarchical structural engineering, anti-fouling interfaces, multi-signal cross-validation, catalytic–recognition integration, and interfacial binding regulation. Representative biomarker cases are analyzed to illustrate how functional modules can coordinate across sample processing, signal generation, and recognition confirmation to improve analytical reliability and overall sensing performance. Finally, the review discusses challenges in clinical translation, including consistent manufacturing, matrix interference, long-term stability, and standardized validation, while outlining future directions toward mechanism-guided imprint design, intelligent data-assisted optimization, and integration with microfluidic and wearable platforms for multiplexed biomarker detection. Full article

The continued evolution of SARS-CoV-2 has enabled an escape from most monoclonal antibodies, yet a subset of broadly neutralizing antibodies targeting three newly identified super-conserved RBD epitopes—SCORE-A, SCORE-B, and SCORE-C—retains remarkable activity against even the most recent JN.1-derived sublineages. Here, we employed an integrated computational framework combining conformational dynamics, mutational scanning, MM-GBSA binding energetics, and frustration profiling to dissect the molecular mechanisms by which XGI antibodies achieve broad neutralization and resistance to immune escape. Structural analysis revealed that all three SCORE epitopes share a common architecture: a highly conserved, minimally frustrated core that provides stable anchoring, flanked by peripheral regions that accommodate antibody-specific variations. Conformational dynamics showed that SCORE-A antibodies (XGI-183) rigidify the lateral epitope while leaving the RBM partially mobile; SCORE-B antibodies (XGI-198, XGI-203) clamp the RBM apex, directly blocking ACE2; and SCORE-C antibodies (XGI-171) allosterically loosen the RBM loop, impairing receptor engagement indirectly. Mutational scanning identified a hierarchical hotspot organization where primary hotspots (e.g., K356, T500, Y380, T385) are evolutionarily constrained and minimally frustrated, while secondary hotspots (e.g., V503, Y508, S383) are neutrally frustrated and represent the principal sites of immune-driven mutations. MM-GBSA decomposition revealed that van der Waals-driven hydrophobic packing dominates binding, with electrostatic interactions providing auxiliary stabilization. Critically, frustration analysis demonstrated that immune escape hotspots reside precisely in zones of neutral frustration—“energetic playgrounds” that permit mutational exploration without destabilizing the RBD—while minimally frustrated cores are evolutionarily locked. The comparative analysis of conformational versus mutational frustration distributions revealed a unifying principle: aligned neutral frustration yields permissive, escape-prone interfaces; decoupling enables the targeting of constrained cores; and the convergence of minimal frustration in both distributions creates invulnerable interfaces. These findings establish that broad neutralization arises not from ultra-high-affinity anchors but from strategic energy distribution across rigid, evolutionarily informed interfaces, providing a roadmap for designing next-generation therapeutics that target the invulnerable cores of viral surface proteins. Full article

Background: Currently marketed hepatitis B vaccines are primarily recombinant protein vaccines. However, their antigen immunogenicity is relatively weak, requiring combination with effective adjuvants to enhance the immune response. The development of novel, highly effective adjuvants is a key strategy for optimizing vaccine performance. Polyinosinic-polycytidylic acid (PolyI:C), a synthetic double-stranded RNA analog, activates TLR3/RLR pathways to enhance T-cell priming and cellular immunity. However, its utility as a sole adjuvant is limited by rapid nuclease degradation and poor cytosolic delivery. Lipid nanoparticles (LNPs), a mature delivery platform, enable high encapsulation efficiency, efficient cellular uptake, and endosomal escape. Objectives: This study aimed to evaluate the adjuvant effect of LNP-encapsulated PolyI:C (LNP-PolyI:C) on the immunogenicity of hepatitis B surface antigen (HBsAg) in vivo. Methods: The colloidal stability of LNP-PolyI:C stored at 2–8 °C for 9 months was monitored using dynamic light scattering (DLS) on a Zetasizer Lab instrument. Serum levels of HBsAg-specific IgG, IgG1, and IgG2a antibodies in immunized Kunming mice were measured by enzyme-linked immunosorbent assay (ELISA). The secretion of HBsAg-specific cytokines by splenocytes was analyzed using flow cytometry and enzyme-linked immunospot (ELISpot) assay. Results: The results demonstrated that the LNP-encapsulated PolyI:C adjuvant significantly increased the secretion of HBsAg-specific IFN-γ, IL-2, and TNF-α by splenocytes, indicating a Th1-biased and cytotoxic T lymphocyte (CTL)-mediated cellular immune response. In addition, this formulation markedly elevated serum titers of HBsAg-specific IgG, IgG1, and IgG2a. Conclusions: These findings underscore the advantages of the LNP-PolyI:C adjuvant in enhancing both humoral and cellular immunity, demonstrating its considerable potential as a novel adjuvant. Full article

In 2023, a highly immunogenic live attenuated vaccine based on the Nigeria 75/1 strain was introduced in Kazakhstan to provide protection against PPR. This study presents the results of a three-year animal trial evaluating the vaccine’s efficacy, safety, and immunogenicity. The novelty of this study lies in the long-term (up to 36 months) evaluation of protective immunity in adult animals, as well as in the comparative analysis of immune responses across different age groups and the assessment of viral suppression following challenge infection. Sheep and goats of different age groups were included, including lambs and kids aged 1.5 and 3 months, as well as adult animals aged 2–3 years. The vaccine was well tolerated following a single immunization, and no clinically significant adverse effects were observed in vaccinated animals, apart from only mild transient local reactions. A strong humoral (IgG) response to PPRV antigens was detected in all groups, with the highest antibody titers observed in young animals. Seroconversion was detected in 100% of vaccinated animals by day 21 post-vaccination. Long-term protective immunity (at least 36 months) was demonstrated in adult animals, whereas in young animals early protection was confirmed at 21 days post-vaccination along with subsequent humoral immune dynamics following a single immunization with a 1.0 mL dose of the vaccine (Nigeria 75/1 strain, titer 10^3.0 TCID₅₀/mL). These findings indicate that the vaccine is well tolerated, highly immunogenic, and provides sustained protection in adult animals while inducing early immune responses in young animals. Full article

Background: Epimedium is a natural herb with immunomodulatory potential, but its vaccine adjuvant properties remain poorly understood. Objective: The aim of this study was to elucidate the adjuvant effects of Epimedium and the underlying molecular mechanisms. Methods: Network pharmacology was used to identify bioactive compounds and targets of Epimedium from the TCMSP database, and immunomodulation-related targets from GeneCards and OMIM. PPI networks, KEGG/GO enrichment, molecular docking, and molecular dynamics (MD) simulations were performed. In vivo, female BALB/c mice were immunized with the Staphylococcus aureus (S. aureus) vaccine subunit HI antigen, either alone or with low- or high-dose icariin (ICA). Serum antibody responses (IgG, IgG1, IgG2a, IgG2b) were measured by ELISA. Survival against lethal S. aureus USA300 challenge was monitored. Results: Network pharmacology predicted 488 targets and 13 pathways. Core targets included IL6, TP53, EGFR, CTNNB1, HIF1A, HSP90AA1, JUN, MTOR, SRC, and AKT1. KEGG/GO analysis indicated involvement of T cell receptor and NOD-like receptor signaling pathways in inflammatory responses. Molecular docking and MD simulations confirmed stable ligand-target binding. Experimental validation showed that ICA significantly enhanced HI-specific antibody responses and induced a Th2-biased humoral immune response (IgG1/IgG2a ratio > 1), which is particularly relevant for vaccines targeting extracellular pathogens such as S. aureus. ICA also improved survival after lethal bacterial challenge. Conclusions: This study identifies potential bioactive compounds, core targets, and key pathways of Epimedium as a vaccine adjuvant. Experimentally, ICA, as a representative component, enhanced HI-specific antibody responses and conferred protection against lethal S. aureus challenge. Together, these findings offer a computational–experimental basis that may guide further mechanistic investigation. Full article

Background and Objectives: Healthcare workers are at heightened risk of SARS-CoV-2 infection. Understanding the duration and protective value of vaccine-induced immunity is critical to inform booster strategies. This study investigates longitudinal dynamics of anti-SARS-CoV-2 receptor-binding domain IgG (anti-RBD IgG) antibodies and their association with infection risk among vaccinated healthcare workers. Materials and Methods: A prospective cohort study was conducted at Vilnius University Hospital Santaros Klinikos, Lithuania. A total of 1778 healthcare workers who completed a primary COVID-19 vaccination series were followed. Blood samples were collected every three months to measure anti-RBD IgG levels. Participants also received up to three booster doses. COVID-19 was identified by PCR, antigen tests, or positive anti-nucleocapsid IgG. For serologically detected cases, infection timing was assigned to the interval between study visits. Antibody dynamics were analyzed across vaccination stages, time, age groups, and circulating SARS-CoV-2 variants. Results: Anti-RBD IgG titers peaked in the first quarter after primary vaccination (mean 7904 AU/mL), declined sharply by quarters 2–3, and rose substantially after booster doses. Following the first booster, titers increased to ~12,598 AU/mL in quarter 1 and continued rising through quarter 3. The highest levels were observed after the second booster (24,456 AU/mL in Q1), followed by gradual decline. A high-titer plateau persisted from quarters 6 to 9 (~21,000 AU/mL), followed by decline in quarters 10–11 and partial rebound in Q12. Approximately 49.6% of participants experienced COVID-19 during follow-up. Antibody response patterns were similar across age groups, with only minor transient differences. Conclusions: COVID-19 booster doses significantly enhance and prolong humoral immunity in healthcare workers compared with the primary vaccination series. However, antibody waning over time emphasizes the need for timely boosters, particularly during periods of variant circulation. These findings support continued booster vaccination and monitoring of long-term immune protection, although anti-RBD IgG should be interpreted as a surrogate marker of humoral rather than overall immunity. Full article

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease in which B-cell dysregulation plays a central pathogenic role beyond autoantibody production. Advances in B-cell biology have led to the development of targeted therapies, including inhibition of the B-cell activating factor (BAFF) pathway. Belimumab, a monoclonal antibody that neutralizes soluble BAFF, modulates B-cell survival signals upstream, promoting progressive immunologic remodeling rather than rapid depletion. This review integrates current knowledge on BAFF-dependent B-cell biology with mechanistic, pharmacokinetic, and clinical data to provide a comprehensive framework for understanding belimumab’s effects in SLE and lupus nephritis (LN). Belimumab preferentially reduces transitional and naïve B cells, while memory B cells show a relative transient increase followed by a gradual return to baseline levels, reflecting redistribution rather than expansion, and long-lived plasma cells are largely unaffected. These effects result in progressive remodeling of B-cell compartment dynamics and contribute to broader modulation of adaptive immune amplification pathways. Pharmacokinetic data support a threshold-based model of BAFF neutralization, with exposure influenced by disease-related factors such as proteinuria in LN. Clinical response is primarily determined by baseline disease biology, with greater benefit observed in patients with serologically active disease and less established organ involvement. Across clinical trials and real-world studies, belimumab reduces disease activity and flares, enables glucocorticoid tapering, and slows organ damage accrual. In LN, it improves renal outcomes and reduces the risk of kidney-related events. Collectively, these findings support belimumab as a disease-modifying therapy in SLE. Further research is needed to refine patient selection and optimize treatment sequencing and combination strategies. Full article