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Slow subcutaneous immunoglobulin therapy in a patient with reactions to intramuscular immunoglobulin.

A 35-year-old man with common variable hypogammaglobulinemia had repeated anaphylactic reactions to intramuscular human immune serum globulin (HISG), preventing him from receiving the injections. He was able to tolerate slow subcutaneous HISG infusions without local or systemic side effects at a dose of 12 ml/week given at a rate of 2 ml/hr. He has been maintained on these infusions for 2 years in an infection-free state.

Long-Term Extensions of Randomized Vaccination Trials of ACC-001 and QS-21 in Mild to Moderate Alzheimer's Disease.

OBJECTIVES: Long-term safety and tolerability of ACC-001 (vanutide cridificar), an antiamyloid- beta therapeutic vaccine, was evaluated in subjects with mild to moderate Alzheimer's disease. DESIGN: Phase 2a extension studies of randomized parent trials were conducted in the United States, European Union, and Japan. METHODS: Four immunizations of ACC-001 were administered at the same 3 dose levels (3, 10, and 30 μg) to subjects randomized in the parent studies; ACC-001 was administered with QS-21 adjuvant. Safety, tolerability, and immunogenicity were assessed during active treatment and 6-m

Reconceptualizing chorioamnionitis as an immune-mediated inflammatory disorder at the maternal-fetal interface.

BACKGROUND: Chorioamnionitis has long been regarded as an infection-driven obstetric disorder, yet converging clinical, pathological, and mechanistic evidence demonstrates that host-derived inflammatory pathways, together with microbial factors, critically shape placental injury, fetal involvement, and neonatal outcomes. Histological inflammation of the chorioamniotic membranes correlates more strongly with adverse outcomes than microbial detection alone, underscoring the importance of host immune responses even in the context of microbial invasion. PURPOSE: This review aims to synthesize cur

HLA-DRB1*15:01 drives sex- and age-dependent microglial immune phenotypes and neuroimmune signaling.

INTRODUCTION: The major histocompatibility complex class II (MHC-II) pathway is central to adaptive immunity and immune tolerance, and its age-related dysregulation is increasingly linked to chronic neuroinflammation. The HLA-DRB1*15:01 allele, the strongest genetic risk factor for multiple sclerosis, has been implicated in shaping pathogenic CD4+ T-cell responses and broader neuroimmune vulnerability, yet how this allele modulates age- and sex-dependent neuroimmune processes within the central nervous system (CNS) remains poorly defined. METHODS: We investigated the impact of HLA-DRB1*15:01 …

Immune-related toxicity and soluble profile in patients affected by solid tumors: a network approach.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have particular, immune-related adverse events (irAEs), as a consequence of interfering with self-tolerance mechanisms. The incidence of irAEs varies depending on ICI class, administered dose and treatment schedule. The aim of this study was to define a baseline (T0) immune profile (IP) predictive of irAE development. METHODS: A prospective, multicenter study evaluating the immune profile (IP) of 79 patients with advanced cancer and treated with anti-programmed cell death protein 1 (anti-PD-1) drugs as a first- or second-line setting was perform

Thymic function as a central determinant of immune competence and clinical outcomes.

The thymus is a central regulator of immune competence, sustaining the continuous generation of a diverse and self-tolerant T-cell repertoire throughout life. Although traditionally regarded as primarily relevant during early development, accumulating evidence highlights its persistent role in shaping adaptive immunity across physiological and pathological conditions. In this review, we examine the role of thymic function as a determinant of immune competence and treatment efficacy across conditions in which adaptive immunity is challenged or therapeutically reshaped, including hematopoietic c

Both host and parasite non-coding RNAs co-ordinate the regulation of macrophage gene expression to reduce pro-inflammatory immune responses and promote tissue repair pathways during infection with fasciola hepatica.

Parasitic worms (helminths) establish chronic infection within mammalian hosts by strategically regulating their host's immune responses. Deciphering the mechanisms by which host non-coding RNAs (ncRNA) co-ordinate the activation and regulation of immune cells is essential to understanding host immunity and immune-related pathology. It is also important to comprehend how pathogens secrete specific ncRNAs to manipulate gene expression of host immune cells and influence their response to infection. To investigate the contribution of both host and helminth derived ncRNAs to the activation and/or

Evaluation of the safety and immunogenicity of a candidate tuberculosis vaccine, MVA85A, delivered by aerosol to the lungs of macaques.

Tuberculosis (TB) is a reemerging disease. The only available vaccine, Mycobacterium bovis BCG, is delivered intradermally and confers highly variable efficacy against pulmonary disease. There is an urgent need for improved vaccination strategies. Murine studies suggest that immunizations delivered directly to the respiratory mucosa might be a more effective route of vaccination. This study compared the immunogenicity of a leading candidate tuberculosis (TB) vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in rhesus macaques, delivered either as an aerosol or as an intr

Peripheral neuron circuitry mediating pain in head and neck cancer.

PURPOSE OF REVIEW: Pain is a major source of morbidity in head and neck cancer (HNC), yet its neural mechanisms remain incompletely defined. This review examines how malignant cells, the tumor microenvironment, and cancer treatment remodel peripheral sensory and autonomic circuits, and how neural activity reciprocally influences tumor biology, with particular attention to findings published since 2023. RECENT FINDINGS: Recent studies show that HNC selectively reorganizes tumor-associated nerves rather than merely injuring a pre-existing neural scaffold. Sensory-neuron transcriptional response

Inflammation as a central driver in AML pathogenesis and therapy resistance.

Inflammation is a prominent feature of the bone marrow microenvironment in acute myeloid leukemia and contributes to leukemic evolution, progression, and therapeutic resistance. Accumulating evidence indicates that inflammatory signals in AML arise from multiple sources, including age-associated inflammaging, mutation-driven pathways, cell-intrinsic stress programs, and external inflammatory stimuli such as infections. These signals collectively facilitate the progression from clonal hematopoiesis and other pre-leukemic states to overt leukemia and support malignant expansion. Leukemic blasts,

Fermentation-Derived Metabolites Shape Host Biology to Attenuate Severity of Inflammatory and Metabolic Disease.

Fermented foods are among the few dietary interventions shown to increase gut microbiome diversity and reduce systemic inflammation in healthy adults, yet the underlying mechanisms remain poorly defined. Metabolites produced during food fermentation, termed fermentation-derived metabolites (FDMs), represent a largely uncharacterized pool of bioactive compounds that may directly mediate the physiological effects of fermented food consumption. Here, we characterize the metabolite landscape of ten vegetable-based fermented foods using metabolomics, identifying conserved enrichment of aromatic and

scFv-based biologics in diabetes: from therapeutic potential to clinical prospects.

The global epidemic of diabetes mellitus the limitations of current therapies-including waning efficacy, adverse effects, and inability to m … e highlight the unique value of avian-derived scFv in recognizing conserved epitopes and overcoming immune tolerance, along with engineering strategies-such as Fc fusion, PEGylation, and multispecific formatting-that enhance pharmacokinetics and therapeutic efficacy. The clinical success of antibodies like Teplizumab underscores the translational potential of anti …

Radiotherapy disrupts ferroptosis tolerance by reducing DNMT1 levels and uncouples STING silencing in LKB1-deficient lung tumors.

Liver kinase B1 (LKB1) deficiency confers primary resistance to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer; however, the underlying mechanisms remain unclear. Through single-cell RNA sequencing analysis of a genetically engineered KrasG12D/+-driven mouse model with a conditional Lkb1 knockout, we discovered that LKB1-deficient tumors display dysregulation of the ferroptosis pathway. Analyses of multiple clinical cohorts revealed that LKB1-deficient lung tumors exhibit elevated ferroptosis resistance scores, which contribute to immunotherapy failure. Subsequent in vitro a

Regulatory T cell dysfunction and exhaustion in uveitis: immunometabolic mechanisms, microenvironmental drivers, and emerging therapeutic strategies.

Non-infectious uveitis encompasses a diverse array of autoimmune ocular disorders marked by the breakdown of immune tolerance and recurrent inflammatory episodes. Regulatory T cells (Tregs) are integral to the maintenance of ocular homeostasis in all subtypes of this condition. However, Behçet's disease, Vogt-Koyanagi-Harada (VKH) disease, and HLA-B27-associated uveitis exhibit distinct patterns of Treg quantitative reduction, lineage instability, and functional exhaustion. Tregs play a crucial role in maintaining ocular homeostasis; however, their quantitative reduction, lineage instability, …

MYC-Driven Glycolysis in TNFRSF4+ CD4+ T Cells Underlies Heightened Rejection Susceptibility of Cardiac vs. Renal Allografts.

BACKGROUND: Cardiac allografts show poorer long-term survival and decreased tolerance compared to renal allografts, but the underlying mechanisms remain unclear. METHODS AND RESULTS: We established heterotopic heart and kidney allotransplantation models in Bama miniature pigs. Single-cell RNA sequencing (scRNA-seq) was performed to analyze normal heart/kidney tissues and allografts. Transcription factor analysis focused on T-cell subsets, with key findings validated using clinical human heart tissues (normal vs. acute rejection) and a mouse heart transplantation model (to test MYC inhibition)

Beyond the genetic code: orchestrating epigenetic and immune landscapes with multivalent mRNA-exosome vaccines.

mRNA therapeutics are transitioning from transient anti-viral vaccines into precise cancer immunotherapies capable of orchestrating potent a … r detail how vaccine-induced cytokine fluxes actively remodel the TME, successfully reversing local immune tolerance and driving robust effector leukocyte infiltration into the tumor stroma. Specifically, we highlight the convergence of mRNA-mediated cytokine signaling and epigenetic imprinting, which cooperatively induce trained immunity for durable preventive su …

Application and Challenges of Chimeric Antigen Receptor T Cell Therapy in Systemic Rheumatic Diseases and Autoimmune Disorders.

Chimeric antigen receptor T (CAR-T) cell therapy, originally developed for hematologic malignancies, has emerged as a transformative candidate for systemic rheumatic diseases and autoimmune disorders (AIDs). Its unique efficacy in refractory AIDs relies on depleting autoreactive B cells and driving antigen-naïve immune reconstitution, achieving durable drug-free remission in early-phase trials. Despite promising clinical and serological responses lasting 2-5 years without long-term immunosuppression, the field faces unmet needs: complex manufacturing, limited tissue penetration, antigen escape

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… tolerance. … Therefore, CAR‐T cells, through deep B cell depletion strategies, can achieve long‐term immune tolerance in autoimmune neurological diseases, eliminating the need for continuous immunosuppressive treatments. …

Extracellular Vesicles from Lactic Acid Bacteria: Emerging Postbiotic Effectors in Host-Microbe Crosstalk.

This article addresses extracellular vesicles derived from lactic acid bacteria (LAB-EVs), which have become fundamental mediators of host-m … on, and the regulation of tight junction proteins, which collectively sustain barrier integrity and immune tolerance. Furthermore, we discuss the therapeutic implications of LAB-EVs in inflammatory bowel disease, epithelial repair, and systemic tissue regeneration. Despite these promising findings, significant obstacles remain in standardizing isolation methods, c …

Alternative splicing of CD244 restrains natural killer cells at the maternal-fetal interface.

Decidual natural killer (dNK) cells are the predominant lymphocyte population at the maternal-fetal interface during early pregnancy, where they support placentation, vascular remodelling and immune tolerance. Despite their abundance, the mechanisms governing their proliferative state remain poorly understood. Here, we show that first-trimester dNK cells reside in a stable non-cycling state characterized by G0/G1 arrest, suppression of proliferation-associated transcriptional programmes and attenuated kinase signalling. Unlike peripheral blood NK (pNK) cells, dNK cells did not proliferate in r…

The Evolving Landscape of Extracorporeal Photopheresis in Immunotherapy: A Comprehensive Bibliometric and Topic Modeling Analysis (1995-2024).

INTRODUCTION: Extracorporeal photopheresis (ECP) is an established immunomodulatory therapy for graft-versus-host disease (GVHD) and cutaneo … atory mechanisms. Topic 6 captured mechanistic research on apoptosis and regulatory T-cell-mediated immune tolerance. Contextual prospective evidence in GVHD and irAEs suggested corticosteroid-sparing activity and generally favorable tolerability, but was limited by small cohorts, heterogeneous schedules and endpoints, and few randomized comparisons. CONCLUSION: …