Scandinavian Journal of Immunology最新文献

The link between allergic conditions and common variable immunodeficiency (CVID) is still unclear. Only a few studies suggest allergic diseases are more prevalent in CVID patients than in the general population, and the role of IgE remains poorly defined. This study aims to evaluate the prevalence of allergic conditions in CVID and the role of serum IgE and IgA levels. This prospective, cross-sectional, case-control study enrolled Italian adult CVID patients to investigate allergic conditions' frequency and relationships between IgE, IgA, and clinical phenotypes. Analyses of diagnostic/prognostic accuracy were performed with ROC curves. We documented an allergic disease in 26.6% of 60 CVID patients, most commonly allergic rhinitis (56.2%) and bronchial asthma (12.5%). CVID patients with allergy had higher IgE levels (+8.9 kU/L, p = 0.006) than non-allergic ones, but lower than allergic individuals without CVID. IgE deficiency was observed in 65% of CVID patients, with a strong correlation between IgE and IgA levels (r = 0.7, p < 0.001). Low IgE (< 2.5 kU/L) and IgA levels (< 7 mg/dL) were significantly associated with lymphoproliferative (p < 0.001) and granulomatous phenotypes (p = 0.005), achieving an AUC of 94% and 81% for predicting lymphoproliferation and granulomatosis, respectively. The prevalence of allergic conditions in CVID patients is lower compared with previous studies. Low IgE levels served as a good biomarker for CVID and CVID-phenotypes. Combined serum IgE and IgA assessment improved prognostic stratification.

Interleukin-40 (IL40) is a recently described 27 kDa cytokine encoded by C17orf99, originally suggested to play a role in B-cell biology, but its function is largely unknown. However, elevated serum levels have been reported in rheumatic diseases. Most published studies focus on IL40 measurements in serum/plasma using commercial sandwich ELISAs. Here we found large discrepancies between two IL40 ELISAs (Mybiosource and Abbexa), with Abbexa reporting significantly higher plasma levels. In our investigation, IL40 (Abbexa) was not elevated in patients with ANCA-associated vasculitis, early or established rheumatoid arthritis (RA), or RA patients who had developed B cell lymphoma (RA-L), compared to healthy donors. Yet, we found significant correlation of Abbexa IL40 levels with BAFF and APRIL. We next compared the binding of IL40 between the two commercial assays. Pre-adsorption experiments showed that the Mybiosource capture antibody bound the same target as the Abbexa capture antibody but did not detect the same IL40. Moreover, neither assay detected the reciprocal IL40 kit reference nor mammalian expressed recombinant IL40. In contrast, a Human Protein Atlas (HPA) antibody towards the unstructured C-terminal of IL40, despite being only partly validated by HPA, detected recombinant IL40 in Western blot and ELISA. We speculate that there may be different structural or modified forms of IL40. The discrepancy between the IL40 Abbexa results and the literature also highlights the difficulties in interpreting results from commercial antibodies and assays.

Cancer remains one of the most pressing global health challenges due to its high incidence and mortality. Intratumoral and intertumoral heterogeneity pose significant challenges to effective treatment, driving metastasis, recurrence, therapeutic resistance and ultimately treatment failure. The development of precision medicine urgently requires in vitro models that can faithfully capture patient-specific tumour complexity to guide individualised therapies. Recent advances in stem cell-based three-dimensional culture technologies have facilitated the establishment of organoid systems that closely replicate the architecture, molecular features, genomic alterations and microenvironment of primary tumours. Compared with conventional cell lines, organoids exhibit superior fidelity, making them a transformative platform for cancer modelling. They hold considerable promise for high-throughput drug screening, therapeutic response prediction, biomarker discovery and the design of personalised treatment strategies. Despite these advances, clinical translation is still hindered by challenges, such as the lack of standardisation, prolonged culture periods, high costs and regulatory and ethical constraints. This review summarises recent progress in tumour organoid research, with particular emphasis on their ability to replicate the genetic and biological features of parental tumours. We highlight their translational applications in immunotherapy, drug sensitivity prediction and individualised treatment, while also proposing strategies to address current limitations aiming to accelerate the integration of organoid technologies into precision oncology.

Immune checkpoint inhibitors (ICIs) have reshaped cancer treatment, offering durable remissions for a minority of patients. Yet their success has come with a difficult trade-off: a large proportion of patients develop immune-related adverse events (irAEs), sometimes severe, and often without gaining clinical benefit. These reactions signal a disruption of peripheral tolerance that is not easily explained by traditional models in which negative selection of autoreactive T cells maintains self-restraint. Under ICI therapy, patients' own T cells can behave in ways that resemble the alloreactive responses seen in chronic graft-versus-host disease (cGVHD), producing a pattern of tissue injury that mirrors this well-studied transplant complication. This parallel offers a fresh way to think about why irAEs occur and how they might be prevented. Despite arising from fundamentally different immunologic triggers, comparative transcriptomic analyses reveal that cGVHD and irAEs induced by ICIs converge on a common molecular ecosystem dominated by interferon-conditioned tissue states. Early clinical experience with ultra-low-dose ICI regimens supports this idea, showing that meaningful antitumor activity can be preserved while dramatically reducing toxicity. We suggest that viewing ICI-induced autoimmunity through a cGVHD-like lens may help guide safer dosing strategies and broaden access to immunotherapy worldwide.

Jeffrey Modell warning signs have been used to guide screening for inborn errors of immunity (IEIs) for over three decades now, but may lack sensitivity for noninfectious presentations. Our study explored JMF signs along with additional signs and some laboratory parameters and assessed their effectiveness for guiding molecular screening for IEIs. We retrospectively analysed 100 patients suspected of IEI referred to ICMR-National Institute of Immunohaematology from immunology clinics who underwent whole-exome sequencing (WES), with pathogenic (n = 50) and no variants (n = 50). We evaluated clinical presentations other than JMF-autoimmunity, autoinflammation, vaccine complications, fever with bi-cytopenia, consanguinity and laboratory parameters-absolute lymphocyte count, low naïve T cell (%) and hypogammaglobulinaemia at initial presentation. Thirty-two models with different combinations of additional signs along with JMF score were evaluated based on the AIC score to determine the best model. The model was validated on WES results of 219 patients. The JMF scores of the pathogenic/likely pathogenic group (3.54 ± 1.92) were significantly higher than those of the no variants group (1.34 ± 1.28) (p < 0.05). The best model, inclusive of consanguinity, presence of autoimmunity, vaccine complications, hypogammaglobulinaemia and low naïve T cell (%) with JMF, had a sensitivity and specificity of 82% and 67%, respectively, compared to sensitivity and specificity of 84% and 61% for JMF alone. Our study shows that the presence of any two among parental consanguinity, presence of autoimmunity, vaccine complications and low naïve T cell (%) improves the specificity of JMF criteria in guiding molecular screening for IEIs.

Helminthiasis refers to infections caused by parasitic worms, which represent a significant global health burden, particularly in tropical and subtropical regions. The pathophysiology of helminth infections is highly complex, largely due to the intricate interactions between the host's immune system and the parasite's sophisticated immune evasion strategies. These parasites can modulate host immunity to ensure their long-term survival, often inducing regulatory responses that hinder both natural immunity and vaccine development. However, in recent decades, new vaccine candidates have emerged that show promise in combating these infections. Therefore, the aim of this review is to describe the host immune response to helminth infections, examine the mechanisms by which helminths evade immune detection, and explore advances in vaccine development as a strategy for controlling these neglected diseases.

Diabetes mellitus (DM) is a chronic metabolic disorder characterised by persistent hyperglycemia, systemic metabolic dysfunction and insulin resistance (IR). Recent progress in the interplay between the immune system and metabolism highlights the critical role of immune dysregulation in the pathogenesis of IR and type 2 diabetes mellitus (T2DM). This review explores the immunopathogenic mechanisms underlying IR and the potential immunotherapies to modulate these pathways, with a focus on immune cells, inflammatory mediators and immune checkpoint regulation. Recent advances in immunotherapy have opened new avenues for restoring metabolic homeostasis and improving insulin sensitivity. Targeted approaches, including monoclonal antibodies against TNF-α, IL-1β and IL-6, have been reported to have antifibrotic and anti-inflammatory effects, reducing inflammation-driven insulin resistance. Additionally, inhibitors of NF-κB, JAK/STAT and JNK signalling pathways have been reported to enhance insulin sensitivity. Immunoregulatory therapeutics using MSC (mesenchymal stem cell) and Treg (regulatory T cell) therapy and cytokine vaccine-based vaccines are emerging as innovative therapeutic options for T2DM. Despite these advances, problems such as immune-related toxic reactions, patient and individual-specific variability, and the requirement for precision medicine approaches persist as obstacles to translational application from the clinics to industry levels. In this review, an overview of preclinical and clinical evidence for immunotherapeutic approaches to IR is described, and recommendations for future developments in integrating these therapies into personalised diabetes management are provided. Targeting immune-mediated inflammation with immunotherapies can lead to a new era in T2DM therapy, which will provide new approaches to enhance insulin sensitivity and glycemic control.

The discovery of natural killer (NK) cells stands among the fundamental milestones in modern immunology. To mark the 50-year anniversary of the first publications on NK cells in 1975, a symposium was held at Karolinska Institutet in Stockholm, Sweden, on October 14, 2025. The symposium brought together scientists from across generations to reflect on the field's historical roots and future directions. The meeting traced NK cell research from its serendipitous beginnings with the identification of a previously unknown lymphocyte population capable of mediating spontaneous cytotoxicity to the conceptual proposal of 'missing self' recognition. Subsequent studies established the role of the first inhibitory receptor Ly49A. This was followed by the discovery of NK cell killer-cell immunoglobulin-like receptors (KIRs), along with a range of associated inhibitory and activating receptors, providing further insights into NK cell target recognition. The symposium then highlighted how advances in genetics, cell imaging and single-cell technologies have revealed NK cell diversity, tissue specialisation and adaptive potential. It showcased insights from rare immunodeficiencies, tumour immunology, viral immunology and systems-level analyses, underscoring NK cells' dual roles in cytotoxic defence and immune regulation. Increasingly, artificial intelligence (AI) is being leveraged in NK cell research. Translational developments described have bridged fundamental knowledge with clinical application, exemplified by current clinical studies of engineered NK cells, NK cell engagers and checkpoint blockade strategies. Together, these reflections underscored how five decades of NK cell research, rooted in seminal Scandinavian discoveries, have transformed from an unexpected observation into a cornerstone of immunotherapeutic potential.