npj Vaccines

Vaccination frequently elicits suboptimal immunogenicity in organ transplant recipients, particularly those on long-term immunosuppressive therapy, highlighting the need for improved understanding of immunosuppression mechanisms and optimized vaccination strategies. This study enrolled a cohort of 132 individuals and observed significantly lower antibody levels in kidney transplant recipients (KTRs) compared to non-transplant controls (non-KTRs). Antibody levels were inversely associated with bo...

BackgroundIron metabolism disorder is highly prevalent before and after heart transplantation (HTx). The impact of pretransplant and posttransplant iron disorder on posttransplant outcomes is unclear. ObjectivePretransplant serum levels of key regulator proteins of iron metabolism (hepcidin, interleukin-6, erythroferrone) were tested for prediction of the composite outcome 1-year posttransplant all-cause mortality (ACM) or [≥]moderate acute cellular rejection (ACR). Furthermore, serum levels...

Multiple sclerosis (MS) therapies primarily rely on lymphocyte depletion or trafficking blockade, carrying risks of systemic immunosuppression; however, such treatments have limited efficacy in secondary progressive multiple sclerosis (SPMS). Thus, drugs that target stage-specific inflammation without broad immunosuppression are an unmet clinical need. In this double-blind, placebo-controlled phase II trial, 30 patients with relapsing MS received weekly oral OCH or placebo for 24 weeks. In the ...

Immune checkpoint inhibitors (ICIs) have transformed cancer treatment but commonly cause immune-related adverse events (irAEs), whether administered as monotherapy or in combination with other oncological agents. We present the first reported case of ICI-induced granulomatous sialadenitis in a male patient in his mid-fifties with BRAF-V600E-mutated papillary thyroid carcinoma who received sequential treatment with BRAF/MEK inhibitors followed by pembrolizumab. The patient experienced acute-onset...

BackgroundPeanut allergies continuously present urging public health challenges. Oral immunotherapy (OIT) is an important treatment option for peanut allergies, but its effectiveness varies, in terms of inducing desensitization (DS) or achieving long-term sustained unresponsiveness (SU). Identifying biomarkers to predict OIT outcomes is thus of great translational interests. MethodsWe thoroughly analyzed data from the POISED trial and our in-house OPIA trial, with a particular focus on the pean...

BackgroundIn lung transplantation, de novo immunodominant donor-specific anti-HLA antibodies recognizing HLA-DQ antigens (dn-iDSA-DQ) are predominant and can induce chronic lung allograft dysfunction (CLAD). We previously developed a method to measure the active concentration of dn-iDSA-DQ. We aimed to determine whether this new quantitative biomarker is associated with transplantation outcomes. MethodsThis retrospective multicentre cohort study included 90 lung transplant recipients (LTRs) dev...

The Endoplasmic Reticulum AminoPeptidase 2 (ERAP2) gene encodes an aminopeptidase involved in antigenic peptide processing for the MHC-I pathway. Genetic variants in the ERAP2 gene are associated with autoimmune conditions and infectious diseases. The linkage between genetic variants in the ERAP2 gene has given rise to the prevailing assumption that a single ERAP2 allotype with invariant amino acid sequence accounts for all immunological functions of ERAP2. Here, we show by analyzing exon-sequen...

Epstein-Barr virus (EBV) is strongly implicated as an essential environmental trigger of multiple sclerosis (MS), yet the host genetic mechanisms governing EBV activity and how infection triggers the disease are not known. We developed a pipeline to quantify EBV DNA from whole-genome sequencing data and applied it to population-scale cohorts. Using this pipeline, we performed a cross-ancestry genome-wide association study (GWAS) of EBV DNA positivity in 617,186 individuals and identified 39 inde...

AimsGestational diabetes mellitus (GDM) is the most common pregnancy-related medical complication. GDM is linked to aberrant immune responses in both mothers and offsprings, specifically, the subsequent development of inflammatory diseases. Whereas prior research has focused on specific immune cell subsets, a comprehensive overview of the impacts of GDM on maternal and fetal immune landscape is lacking. Here, we aim to comprehensively decipher how GDM modulates various immune cell populations in...

BackgroundGastroenteric tract requires robust tolerogenic mechanisms to tolerize foreign antigens like foods and microbiota. This is critical to establish the immune homeostasis, which upon disruption, might contribute to a plethora of atopic disorders, including food allergy and eosinophilic esophagitis (EOE). Recently, there was a new subset of tolerizing dendritic cells (tolDCs), PRDM16 tolDC, discovered in the gut of mice and humans, which confers protection against food allergy. Whether an ...

RIG-I is a cytosolic immune receptor that provides the first line of defense by detecting viral RNA and triggering antiviral responses. Its physiological role in humans remains unclear, as no patients with complete RIG-I deficiency have yet been reported. We identified a critically ill COVID-19 patient with severe RIG-I deficiency caused by heterozygous RIG-I G731R, a novel dominant loss-of-function variant. The G731R mutation in helicase motif VI disrupts the arginine finger, impairing the ATPa...

BK polyomavirus (BKPyV) is a major complication in kidney transplant recipients (KTR), for whom no specific antiviral therapy is available. Modulation of immunosuppressive therapy results in virus clearance in most KTR with BKPyV DNAemia (controllers), but a significant minority fail to clear the virus (non-controllers). Here, we adapt LIBRA-seq, which links antibody sequence data to antigen specificity, to intact viral capsids of the four BKPyV genotypes to study and compare BKPyV-specific B-ce...

A new H3N2 variant (named subclade K) possesses several key hemagglutinin substitutions and is circulating widely during the 2025-2026 influenza season. In this report, we completed experiments to determine if the 2025-2026 seasonal influenza vaccine elicits antibodies in humans that recognize this variant. We find that H3N2 subclade K viruses are antigenically advanced; however, the 2025-2026 seasonal influenza vaccine elicited antibodies in many individuals that efficiently recognized these vi...

BackgroundAn adverse female sex-bias exists across many autoimmune disorders, yet its underlying mechanisms, particularly the role of sex hormones, remains poorly understood. Furthermore, the physiological influence of sex hormones in regulating T cell function remains undefined. We examined for the critical role of estrogen and progesterone, in regulating CD4+ T cell responses, specifically with respect to inflammation and their bone erosion potential in RA. MethodsInflammatory markers, circul...

ObjectiveThis study aimed to evaluate the efficacy, safety, and optimal strains of probiotics for pediatric allergic rhinitis (AR) using meta-analysis and network meta-analysis. MethodsA systematic search was conducted in databases including PubMed, Web of Science, Cochrane Library, and China National Knowledge Infrastructure up to July 31, 2025, to identify randomized controlled trials (RCTs). Inclusion criteria were pediatric patients with AR, probiotic interventions, control groups receiving...

Antiphospholipid syndrome (APS) and systemic sclerosis (SSc) are immune-mediated multisystem autoimmune diseases with distinct clinical phenotypes but overlapping pathogenic themes, including immune dysregulation, chronic inflammation, and endothelial injury. Using peripheral blood transcriptome datasets from the Gene Expression Omnibus (GSE102215: 9 APS/9 controls; GSE231691: 49 SSc/18 controls), we performed differential expression analysis within each cohort (limma; |log2FC|>1, P<0.05) and id...

Prioritising malaria vaccine targets requires understanding immunity to genetically and structurally diverse parasite antigens, influencing antibody measurements and durability. We measured total IgG levels to 25 Plasmodium falciparum antigens and assessed their association with protection and antigen features. Antibodies were quantified in two longitudinal cohorts of Papua New Guinean children (5-14 years; n=647) experiencing high or moderate transmission. Associations between antibody levels a...

Sjogrens disease (SjD) is a chronic autoimmune disorder characterized by inflammation of the exocrine glands, leading to dry mouth and dry eyes. This study investigates the role of interleukin-9 (IL-9) and T helper 9 (Th9) cells in the pathogenesis of SjD. We found that serum IL-9 levels were significantly elevated in SjD patients and correlated with clinical laboratory parameters, including autoantibody production. In a mouse model of SjD, IL-9 and Th9-associated cytokines were also elevated, a...

BackgroundAtopic dermatitis (AD) is a chronic skin disease that typically occurs in early childhood. In this cross-sectional case-control study, our objective was to employ machine learning approaches to identify novel clusters of protective or susceptibility features associated with AD. Methods and FindingsWe utilised an integrated dataset comprising previously established environmental, cytokine, antibody, and gene expression data from AmaXhosa children, both healthy and with AD, living in ei...

BackgroundCervical cancer is one of the most common malignant tumors of the female reproductive system. Existing treatments provide limited benefit for patients with advanced, recurrent or metastatic disease, and reliable prognostic markers are lacking. In this study we integrated multi-omic data from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) database. Protein-coding genes meeting the criteria of an adjusted P value < 0.05 and |log2 fold-change| > 5 were screened; ...