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关键词： Pregnancy and reproduction   Observational studies/registry   biological DMARD  

关键词： biological DMARD   Tapering   Clinical Trial   Randomized controlled trial   Safety  

关键词： Autoimmune diseases   Cytokine   IL-12   IL-23   IL-35  

摘要： In recent years, the discovery of IL-12 family cytokines, which includes IL-12, IL-23, IL-27, IL-35, and IL-39, whose biological functions directly or indirectly affect various autoimmune diseases. In autoimmune diseases, IL-12 family cytokines are aberrantly expressed to varying degrees. These cytokines utilize shared subunits to influence T-cell activation and differentiation, thereby regulating the balance of T-cell subsets, which profoundly impacts the onset and progression of autoimmune diseases. In such conditions, IL-12 family members are aberrantly expressed to varying degrees. By exploring their immunomodulatory functions, researchers have identified varying therapeutic potentials for each member. This review examines the physiological functions of the major IL-12 family members and their interactions, discusses their roles in several autoimmune diseases, and summarizes the progress of clinical studies involving monoclonal antibodies targeting IL-12 and IL-23 subunits currently available for treatment.

关键词： Targeted synthetic drugs   Real-world evidence   biological DMARD   Glucocorticoids  

关键词： IL-15 superagonists   mRNA delivery   Lipid nanoparticles   Lung-targeting   Cytokine therapy  

摘要： Interleukin-15 (IL-15) emerges as a promising immunotherapeutic candidate, but the therapeutic utility remains concern due to the unexpected systematic stress. Here, we propose that the mRNA lipid nanoparticle (mRNALNP) system can balance the issue through targeted delivery to increase IL-15 concentration in the tumor area and reduce leakage into the circulation. In the established Structure-driven TARgeting (STAR) platform, the LNPLocal and LNPLung can effectively and selectively deliver optimized IL-15 superagonists mRNAs to local and lungs, respectively, in relevant tumor models. As a result, such superagonists exhibited well-balanced efficacy and side-effects, demonstrating the better anti-tumor activity, less systematic exposure, and less cytokine related risks. We finally verified the selective delivery and well tolerability of LNPLung in non-human primates (NHPs), confirming the potential for clinical application. This finding provides new potentials for cancers treatment on lung cancers or lung metastasis cancers.

关键词： acne inversa   bacterial   hidradenitis suppurativa clinical response   hidradenitis suppurativa   hidradenitis suppurativa-related skin pain   HiSCR   immune-mediated inflammatory disease   Janus kinase inhibitors   pain   randomized controlled trial   skin disease   suppuration   upadacitinib   AN   abscesses and inflammatory nodules   HiSCR50   Hidradenitis Suppurativa Clinical Response (defined as at least a 50% reduction in the total abscess and inflammatory nodule count with no increase in abscess count and no increase in draining fistula count relative to baseline)   HS   hidradenitis suppurativa   IL   interleukin   JAK   Janus kinase   NRS   Numeric Rating Scale   NRS30   achievement of a ≥30% reduction and ≥1 unit reduction from baseline in Patient's Global Assessment of Skin Pain   TEAE   treatment-emergent adverse event   TNFi   tumor necrosis factor inhibitor  

摘要： Background: Hidradenitis suppurativa is a disabling inflammatory skin disease. Objective: To investigate the efficacy and safety of upadacitinib, a selective Janus kinase inhibitor. Methods: In this phase 2, randomized, placebo-controlled, double-blind clinical trial (NCT04430855), adults with moderate-to-severe hidradenitis suppurativa were randomized 2:1 to once-daily upadacitinib 30 mg or placebo. At 12 weeks, placebo patients switched to blinded upadacitinib 15 mg, and patients receiving upadacitinib 30 mg continued assigned treatment through week 48. The primary endpoint was $50% reduction in total abscess and inflammatory nodule count with no increase in abscess or draining fistula count relative to baseline (Hidradenitis Suppurativa Clinical Response [HiSCR50]) at week 12. Results: Forty-seven patients received upadacitinib;21 patients received placebo. At week 12, a significantly greater proportion of patients receiving upadacitinib achieved HiSCR50 vs a prespecified historical placebo rate (38.3% vs 25.0%;1-sided P = .018). Comparison with the in-trial placebo group showed an adjusted difference of 14.7% (nominal P = .087). HiSCR50 achievement with upadacitinib was consistent across baseline Hurley stage and prior tumor necrosis factor inhibitor exposure and maintained through week 40. Upadacitinib's safety profile was consistent with previous reports on dermatologic conditions. Limitations: Sample size was small. Conclusion: Findings support further investigation of upadacitinib for moderate-to-severe hidradenitis suppurativa. ( J Am Acad Dermatol 2025;92:1252-60.)

关键词： donor-derived   kidney transplantation   stem cells   urine  

摘要： The incomplete or lack of histocompatibility information constitutes a barrier for the early detection and management of de novo donor-specific antibodies (DSA). To improve the quantity and quality of DNA materials for HLA typing, we developed a non-invasive culture-based method, using DNA extracted from enriched donor-derived kidney stem cells (DKSC) selectively cultured from the urine of kidney transplant receipients (KTR) to allow high-resolution typing by next-generation sequencing. This prospective proof-of-concept study evaluated the feasibility and performance of this approach. DKSC were enriched from the urine of 60 KTRs. DNA extracted from culture-enriched DKSC showed significantly higher concentration and better quality than unbound cells, and with identical short tandem repeat (STR) and 100% concordance compared to that obtained from peripheral blood. Our results suggest that cultured-enriched DKSC are non-invasive and useful for determining HLA and other genes for KTRs where donor information is limited or lacking.

关键词： Psoriasis   IL-23 inhibitors   IL-17 inhibitors   dose spacing   de-escalation   biologics  

摘要： Background and ObjectivesDe-escalation strategies of biologics in psoriasis treatment are widespread in clinical practice. Dose spacing consists of de-escalating the time range between biological drug *** and MethodsMajor objectives were: to describe trends in mean PASI, PASI 100, 90, and <= 1 from baseline to 12 months after dose spacing, provide drug survival analysis of dose-spaced regimens, and concurrently describe phenotypic characteristics related to the selection of patient candidates for therapeutic dose spacing. A pre-post analysis was made between mean PASI at dose spacing and baseline, and after 3, 6, 9, and 12 months following dose *** 1,144 patients treated with IL-23 or IL-17 inhibitors, 61 patients underwent dose spacing. They presented with lower mean baseline Body Mass Index (BMI) (p = 0.011) and PASI (Psoriasis Area Severity Index) (p = 0.044) and were more frequently bio-experienced (p = 0.033). 12 months after dose spacing 42.9%, 85.7%, and 92.9% of observed patients achieved PASI 100, 90, and <= 1. There were no significant differences in mean PASI between dose spacing and subsequent time points. The dose spacing survival was 70% at 1 *** modulation, such as dose spacing, is an effective strategy for most psoriasis patients, resulting in a clear or almost clear skin response that is maintained over time.