Scandinavian Journal of Immunology最新文献

Autoimmune thyroid disease (AITD) is associated with other autoimmune endocrine diseases such as type 1 diabetes (T1D) and celiac disease (CeD). Thyroid peroxidase autoantibodies (TPOA) are biomarkers of AITD but may also occur in patients with other autoimmune diseases. We examined cross-sectional correlations between TPOA and an array of immune markers in a cohort of 90 children with exclusively T1D (n = 27), CeD (n = 16) or a combination of these two diseases (n = 18), compared to a reference group of children without these diagnoses (n = 29). Children with exclusively T1D or T1D in combination with CeD had higher levels of TPOA with an overrepresentation among girls. The correlations between immune markers and TPOA were distinctly different between all study groups. In children with T1D, TPOA correlated mainly with the T helper 1 associated IFN-γ and pro-inflammatory IL-1β. In contrast, in children with combined diagnoses, TPOA was correlated with pro-inflammatory MCP-1, the acute phase proteins ferritin, fibrinogen, and serum albumin A, and adipocytokines resistin and visfatin. Children with exclusively CeD did not show the same strong association between immune markers and TPOA. In conclusion, TPOA positivity was mainly detected in patients with T1D and female sex. Several inflammatory markers correlated with TPOA, indicating a relation to autoimmune parameters in children with T1D, CeD or both, but preceding symptoms AITD.

Cardiovascular diseases (CVDs) remain a leading cause of global mortality, driven by risk factors such as dyslipidemia, hypertension and diabetes. Recent research has highlighted the critical role of inflammasomes, particularly the NLRP3 inflammasome, in the pathogenesis of various CVDs, including hypertension, atherosclerosis, myocardial infarction and heart failure. Inflammasomes are intracellular protein complexes that activate inflammatory responses through the production of pro-inflammatory cytokines such as IL-1β and IL-18, contributing to endothelial dysfunction, plaque formation and myocardial injury. This review provides a comprehensive overview of the structure, activation mechanisms and pathways of inflammasomes, with a focus on their involvement in cardiovascular pathology. Key activation pathways include ion fluxes (K⁺ efflux and Ca²⁺ signalling), endoplasmic reticulum (ER) stress, mitochondrial dysfunction and lysosomal destabilisation. The review also explores the therapeutic potential of targeting inflammasomes to mitigate inflammation and improve outcomes in CVDs. Emerging strategies include small-molecule inhibitors, biologics and RNA-based therapeutics, with a particular emphasis on NLRP3 inhibition. Additionally, the integration of artificial intelligence (AI) in cardiovascular research offers promising avenues for identifying novel biomarkers, predicting disease risk and developing personalised treatment strategies. Future research directions should focus on understanding the interactions between inflammasomes and other immune components, as well as genetic regulators, to uncover new therapeutic targets. By elucidating the complex role of inflammasomes in CVDs, this review underscores the potential for innovative therapies to address inflammation-driven cardiovascular pathology, ultimately improving patient outcomes.

Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and multiple sclerosis (MS) are complex autoimmune inflammatory diseases influenced by genetic, environmental and infectious agents like Epstein-Barr virus (EBV). EBV has been proposed to impact immune pathways through molecular mimicry, diverting antibody reactivity towards host tissues. This review explores the literature on EBV-specific similarities with human peptides and cytokines that might contribute to the onset of RA, SLE and MS. In conclusion, it is vital to conduct experimental computational analyses focusing on the homology between EBV and human proteins to unravel the complexities of autoimmune diseases and advance therapeutic approaches. These insights highlight the significance of collaborative efforts and diverse clinical studies for validation, linking the gap between research and practical applications in the complex field of autoimmunity.

CD1d is an antigen-presenting molecule that presents lipid or glycolipid antigens to iNKT cells, a distinct subset of T lymphocytes characterised by their innate-like properties and restricted use of V_α, J_α and V_β segments. The CD1d-iNKT axis represents an interesting aspect of the immune system with significant potential for therapeutic interventions against infectious diseases. Upon recognition of lipid antigens, iNKT cells initiate rapid and potent immune responses, releasing a diverse array of cytokines such as IL-4, IL-13, IFN-γ etc. that profoundly influence immune reactions against various pathogens, including bacteria and parasites, bridging innate and adaptive immunity. We identify and describe the key features of lipidic antigens and their derivatives that determine the nature of their antigenicity. Furthermore, modulating CD1d-driven iNKT cell responses by an array of lipid and glycolipid antigens holds promise as adjunctive therapy to existing antimicrobial treatments. Understanding the complexities of the CD1d-iNKT axis and exploiting its therapeutic potential in the case of infectious diseases could lead to innovative immunotherapeutic strategies, ushering in a new era of immunotherapy against pathogenic insults.

Autoantibodies against tumour-associated antigens (TAA) are promising biomarkers for cancer diagnosis. This systematic review aims to evaluate the diagnostic values of tumour-associated autoantibodies (TAAbs) in patients with pancreatic cancer. A search was conducted in the PubMed, Web of Science, and Embase databases to collect eligible studies. The primary outcomes included sensitivity, specificity, and accuracy of the test. We used QUADAS-2 to evaluate the risk of bias in the included studies. Meta-analysis was performed using MetaDisc 1.4 and STATA 14.0 software to calculate the combined sensitivity and specificity. A total of 49 articles were included in the final analysis that reported over 100 different TAAbs that were studied for the detection of pancreatic cancer. p53, Ezrin, CLDN17, KCNN3, SLAMF7, SLC22A11 and OR51F2 were the most frequently investigated autoantibodies in these studies. Ezrin exhibited better diagnostic performance with the pooled sensitivity, specificity and summary area under the receiver operating characteristic (SROC) curves being 56%, 88% and 0.90, respectively. Moreover, certain autoantibody combinations achieved substantially higher sensitivity at reasonably high levels of specificity. For example, the combination of Ezrin and ENOA1.2 autoantibodies with CA19.9 yielded sensitivity, specificity and area under the SROC curve of 100%, 92% and 0.96, respectively. TAAb is a promising diagnostic biomarker for early detection of PC, especially when combining TAAb with other markers. The promising candidate markers identified in this review deserve further validation in a broad screening population.

Septic shock is the most severe stage of sepsis. How immune dysregulation contributes to the pathogenesis of septic shock has not been thoroughly understood. In the current research, the phenotype and function of circulating natural killer (NK) cells of septic patients were characterised. The absolute number of NK cells was comparably reduced in septic shock survivors and non-survivors, probably owing to elevated NK cell apoptosis. Activating receptors including signalling lymphocytic activation molecule 4 (SLAMF4), natural killer cell p30-related protein (NKp30), natural killer group 2, member D (NKG2D), and DNAX accessory molecule 1 (DNAM-1) were significantly downregulated on NK cell surface in septic shock patients, especially non-survivors. Furthermore, the patients' NK cells exhibited lower expression of granzyme B and perforin, weaker target cell-induced degranulation and cytokine expression, as well as incompetent cytolytic effect. These alterations were more profound in septic shock non-survivors. Importantly, serum interleukin-35 (IL-35), which is an immunosuppressive cytokine, was remarkably elevated in septic shock patients. Besides, serum interleukin-35 concentration was positively correlated with disease scores but negatively correlated with NK cell activating receptor expression. In vitro assays indicated IL-35-induced strong suppression of NK cell activity, as evidenced by concomitant downregulation of cytokines and activating receptors along with inhibition of cytolytic capacity. Therefore, we uncovered for the first time the contributing role of IL-35 in septic shock-related human NK cell dysfunction.

Vitronectin (Vn) is a complement regulatory component found in humans and a variety of animals. It can inhibit the formation of membrane attack complexes in the complement system. Studies have shown that a variety of pathogenic microorganisms, including Yersinia pestis, dengue viruses, Plasmodium and Candida albicans, may recruit Vn on the surface of pathogens and inhibit the killing effect of the complement system in the host. After entering the body, pathogenic microorganisms may attach to and infect target cells through multiple pathogenic mechanisms. Meanwhile, the body will attack the invading pathogenic microorganisms through its own immune system. However, the immune escape of pathogens will make the host's immune system difficult to respond effectively, thus causing the aggravation of the disease. Therefore, the study of immune escape is of great significance for the treatment, prevention and control of infectious diseases and tumours. In this paper, the mechanism of vitronectin (one of the complement regulatory factors)-mediated immune escape of pathogens is reviewed from multiple aspects.

We aimed to investigate the effects of Salvianolic acid A (SA), an active ingredient of Salvia miltiorrhiza Bunge, on the proliferation, metastasis and CD40-AKT-NF-κB signalling pathway in endometrial carcinoma (EC). Human EC cell lines (Ishikawa and HEC-1A) were treated with varying concentrations of SA, CD40 soluble ligand (sCD40L) or a combination of both. Cell viability, proliferation, invasion and migration were assessed using MTT, colony formation and transwell assays. Flow cytometry was used to analyse apoptosis and cell cycle progression. qRT-PCR evaluated the mRNA level of CD40. The protein expression of CD40, p-AKT, p-mTOR, p-p65, and p52 was evaluated via Western blot and immunofluorescence. A subcutaneous tumour model was used to examine the impact of SA on tumour growth, followed by immunohistochemical analysis of Ki-67, CD40, p-AKT and p-mTOR. SA treatment reduced EC cell viability, proliferation, invasion and migration, while also triggering apoptosis and inducing cell cycle arrest in the G0/G1 phase in a dose-dependent way. These effects correlated with marked downregulation of CD40, p-AKT, p-mTOR, p-p65 and p52 expression. Conversely, activation of CD40 signalling with sCD40L promoted EC cell malignancy and overturned the anti-tumour effects of SA on EC cells. Additionally, SA treatment suppressed tumour growth in xenograft mouse models, along with reduced levels of Ki67, CD40, p-AKT, p-mTOR, p-p65 and p52 in mouse tumour tissues, which were counteracted by sCD40L co-treatment. SA effectively suppresses endometrial carcinoma progression by targeting the CD40-AKT-NF-κB pathway.

Autoimmune polyendocrine syndrome Type-1 (APS-1) is a rare, but severe organ-specific autoimmune disease caused by mutations in the autoimmune regulator (AIRE) gene. Lack of AIRE causes autoreactive T cells to escape negative selection and alters the T regulatory cell subset. However, little is known about how the immune cell subsets vary across the lifespan in APS-1. Here we analysed the peripheral distribution of 13 immune cell subsets along the lifespan using epigenetic quantification. We found the largest discrepancy in immune cells to appear early in APS-1 patients' lives, coinciding with the time point they obtained most of their clinical symptoms. We further revealed longitudinal changes in cell compositions both within the adaptive and the innate arms of the immune system. We found that cell frequencies of B cells, T-cell subgroups, nonclassical monocytes, and Natural Killer cells to be reduced in young APS-1 patients. We also found B-cell frequencies to decrease with ageing in both patients and healthy controls. Our results suggest that Tregs, follicular helper T, and natural killer cells have opposing trends of cell frequencies during life, indicating the importance of considering the age profiles of cohorts which could otherwise lead to conflicting conclusions.