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关键词： coding change   HLA-A*03:509   HLA-C*05:308   NGS  

摘要： Two novel alleles, HLA-A*03:509 and HLA-C*05:308, were identified during routine next generation sequencing.

关键词： Microglial polarization   Electroacupuncture   Ischemic stroke   Cognitive impairment   IL-33/ST2  

摘要： Post-stroke cognitive impairment (PSCI) is a common and debilitating complication of stroke that significantly hinders rehabilitation. Electroacupuncture (EA), which integrates traditional acupuncture with electrical stimulation, has been widely applied in clinical practice and shown remarkable efficacy in treating PSCI. However, its underlying mechanisms remain largely unexplored. The PSCI rat model was established by middle cerebral artery occlusion/reperfusion (MCAO/R). EA treatment commenced 24 h after reperfusion and was administered daily for two weeks. To investigate the role of the Interleukin-33 (IL-33)/Interleukin 1 Receptor-Like 1 (ST2) signaling pathway in EA's therapeutic effects, the ST2 inhibitor Astegolimab (Anti-ST2) was stereotactically injected into the lateral ventricle prior to EA intervention. Neurological function was evaluated using the Zea-Longa neurological deficit score, while emotional and cognitive behaviors were assessed through the open field test (OFT) and novel object recognition (NOR) test. Cerebral infarct volume was quantified using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Protein expression in the striatum was analyzed by Western blotting and immunofluorescence staining, and structural alterations were examined using hematoxylin-eosin (HE) staining. Microglial polarization in the ischemic penumbra was evaluated via double immunofluorescence staining. Serum levels of inflammatory cytokines, including interleukin (IL)-33, IL-10, IL-4, TNF-alpha, IL-1 beta, and IL-6, were determined using enzyme-linked immunosorbent assay (ELISA). EA markedly enhanced learning and memory in stroke rats, upregulated IL-33 expression, promoted M2 microglial polarization, and preserved the integrity of brain white matter. However, blockade of the IL-33/ST2 pathway with Anti-ST2 diminished the therapeutic benefits of EA, aggravated white matter injury and cerebral infarct volume, and amplified the inflammatory response. EA facilitates microgl

关键词： HLA-DPA1*01:238Q   next generation sequencing   novel HLA allele   null allele   third generation sequencing  

摘要： The novel HLA allele HLA-DPA1*01:238Q, detected during routine HLA typing, is most likely not expressed.

关键词： Tuberculosis   Interleukin-12   Interferon-Gamma   Polymorphism   PCR-RFLP   Sudan  

摘要： BackgroundTuberculosis (TB) is a top infectious disease killer worldwide. The susceptibility to infectious diseases, including tuberculosis, has been linked to several cytokine gene polymorphisms. MethodA case-control study was conducted at Abu Anja Chest Hospital, Omdurman, Khartoum state, using PCR-RFLP in 200 Sudanese patients with pulmonary tuberculosis and 200 healthy controls between February 2018 and February 2021. Data analysis was done using the IBM SPSS software package version 20.0. (Armonk, NY: IBM Corp). ResultThe mutant and heterozygous genotypes of IL-12+16974 A/C polymorphism were associated with an almost four-fold [P-value <0.001 OR= 3.703(2.243- 6.115), 95% CI] increased risk of TB in the Sudanese population. No statistically significant differences were found in the genotype and allele frequencies of the IFN-gamma+874T/A gene between patients and controls. ConclusionThese findings suggest, for the first time in Sudan, the significant risk of TB in people carrying the mutant and heterozygous genotypes of IL-12+16974 A/C genes.

关键词： IL-12 family cytokines   Neurodegenerative diseases   Neuroinflammation   Therapeutic targets   Cytokine signaling   Molecular mechanisms  

摘要： Neurodegenerative diseases (NDs) such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) are characterized by progressive neuronal loss and chronic neuroinflammation. Increasing evidence highlights the interleukin-12 (IL-12) cytokine family-including IL-12, IL-23, IL-27, and IL-35-as central regulators of immune responses in the central nervous system (CNS). IL-12 and IL-23 predominantly promote pro-inflammatory pathways by driving Th1/Th17 activity, microglial activation, and neurotoxicity, whereas IL-27 and IL-35 exert anti-inflammatory and neuroprotective effects through IL-10 induction and expansion of regulatory immune subsets. This review synthesizes disease-specific expression patterns and experimental findings, underscoring the dual pathogenic and protective roles of these cytokines. Therapeutic strategies targeting IL-12 family signaling have shown promise in preclinical and clinical contexts. In AD, blockade of IL-12/IL-23 reduced amyloid burden and improved cognition, while agents such as tadalafil and bergapten enhanced IL-27-mediated neuroprotection via PI3K/Akt, Wnt/beta-catenin, and cGMP/PKG pathways. In MS, approaches including p40 blockade (ustekinumab, ABT-874), interferon-beta therapy, hematopoietic stem cell transplantation, and B-cell depletion (ocrelizumab) variably suppressed IL-12/IL-23 and augmented IL-27/IL-35, influencing relapse rates and progression. Natural compounds such as curcumin, berberine, and vitamin D further highlight metabolic and dietary opportunities for cytokine modulation. In PD, combinatorial regimens combining herbal formulations with anti-inflammatory agents dampened IL-12-driven macrophage activation and supported dopaminergic neuron survival. Taken together, IL-12 family cytokines emerge as both biomarkers and therapeutic targets in NDs. However, context-dependent activity, blood-brain barrier constraints, and incomplete understanding-particularly of

摘要： Studying the characteristics of T cell activation and cytokine secretion is crucial for understanding the cell-mediated immunological response (CMI). To assess this purpose, we present a droplet-based single-cell immunoassay platform, named Drop-SCIA, which uniquely integrates surface-enhanced Raman spectroscopy (SERS) with homogeneous-phase immunoassay, enabling highly sensitive, multiplexed cytokine detection at the single-cell level and offering superior target enrichment efficiency compared to the widely used interface-based ELISpot assay. Using this platform, we analyzed Jurkat T cell activation and further profiled IL-2 and IFN-gamma secretion following coculture with normal breast epithelial cells (MCF-10A) and breast cancer subtypes (MCF-7, MDA-MB-231). The platform enables robust and reliable single-cell immune profiling of Jurkat cells, allowing precise assessment of their activation status. Significant differences in IL-2 and IFN-gamma secretion were observed under different coculture conditions, indicating that distinct breast cancer subtypes exert differential effects on T cell activation and function. By combining microdroplet microfluidics with SERS-based signal readout, Drop-SCIA represents a significant technological advancement in the study of CMI within tumor microenvironments. It will aid in the precise analysis of T-cell immune function for vaccine development, cancer immunotherapy, and the diagnosis and treatment of viral and other infectious diseases.

关键词： IFNγ   IL-15   atopic dermatitis   human skin   inflammation   macrophages   psoriasis   skin diseases  

摘要： Interleukin (IL)-15 is primarily known as a pro-inflammatory and anti-apoptotic cytokine, which stimulates the proliferation and survival of key immunocytes, including macrophages (MACs). Yet, it remains unclear how IL-15 specifically impacts MACs in intact human skin, particularly immunoinhibitory, IL-10-producing/secreting M2 MACs (CD206IL-10). In the current pilot study, we explored this in organ-cultured healthy human eyelid skin in the presence of IFNγ (100 IU/mL) to mimic a pro-inflammatory signaling milieu found in several chronic immunodermatoses. Quantitative immunohistomorphometry showed that IFNγ significantly reduced the number of CD68MACs, M2 CD206MACs, and immunoinhibitory CD206IL-10MACs. Moreover, co-administering recombinant human (rh) IL-15 after inducing inflammation by IFNγ largely reversed the IFNγ-induced decline in MAC populations. To investigate if this was mediated via the private IL-15 receptor alpha (IL-15Rα), we successfully silenced IL-15Rα in human skin ex vivo. Indeed, co-administration of IL-15Rα siRNA abrogated the rhIL-15 protection of M2 CD206MACs against IFNγ, but not of the CD206IL-10MAC subpopulation. These pilot data suggest that IL-15 maintains immunoinhibitory M2 CD206IL-10MACs in human skin under IFNγ-dominated inflammatory conditions. Therefore, it deserves to be explored whether IL-15 or IL-15Rα agonists can exert therapeutic benefit in chronic inflammatory dermatoses by preserving the intracutaneous pool of anti-inflammatory dermal M2 MACs.

关键词： desmoplakin   interleukin-1   myopericarditis   BNP   brain natriuretic peptide   DSP   desmoplakin   hs-TnI   high-sensitivity troponin I   IL   interleukin   LVEF   left ventricular ejection fraction  

摘要： Acute myopericarditis in patients with pathogenic desmoplakin (DSP) variants are associated with a high risk for heart failure and cardiac arrhythmias. We present the case of a 25-year-old woman who presented with recurrent myopericarditis with chest pain and elevated troponin I levels despite escalating prednisone therapy. Genetic testing revealed a pathogenic variant in DSP along with a pathogenic variant in KCNQ1 associated with long-QT syndrome and a NOD2 variant associated with an increased risk for Crohn disease. A subcutaneous implantable cardioverter-defibrillator was implanted. The patient was started on the interleukin-1 inhibitor rilonacept, resulting in a significant reduction in symptoms and troponin I levels and the ability to wean off prednisone. Nine months after initiating rilonacept, the patient remained asymptomatic, had been off prednisone for 8 months, and demonstrated improved exercise tolerance and normalized troponin I levels. This case highlights the potential benefit of interleukin-1 blockade in managing DSP-related recurrent myopericarditis.

关键词： CAR T cells   antigen escape   tandem bispecific CAR   IL13Rα2 – B7-H3   computational structure prediction   antibody engineering   cell surface expression optimization   linker engineering   expression fitness score   protein engineering  

摘要： Chimeric antigen receptor (CAR) T cell therapy is a highly effective treatment for multiple malignancies. However, one limitation is tumor antigen-heterogeneity and downregulation, which allows tumor cells to evade conventional, monospecific CAR T cells. One approach to overcome this tumor escape is by utilizing a tandem CAR recognizing two antigens. However, tandem CAR constructs often require optimization to achieve cell surface expression and function. Herein, we describe our process of designing an IL-13Rα2–B7-H3 tandem CAR. Interestingly, our original tandem CAR failed to express on the cell surface, leading to a systematic evaluation of 24 tandem constructs varying in their scFv positioning, linkers, and specific amino acids. We identified a “trouble region” in the CAR and optimized it using computational approaches, rescuing surface expression and improving function compared with monospecific CAR T cells. Further, the optimized tandem CAR T cells more effectively eliminated tumors than monospecific CAR T cells in vivo . Our study demonstrates the successful application of structure-guided computational strategies to restore surface expression and antitumor efficacy of an IL13Rα2 – B7-H3 tandem CAR. Our study also highlights the necessity of computational methods to guide the design of synthetic proteins, and that these methods can increase CAR T cell efficacy.