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.

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.

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.

To determine leptin's effect on the thymus, we gathered data on leptin levels, ghrelin, cortisol and cytokine levels. The aim of the study was to map leptin's effect on the thymus when malnourished. Pubmed and Embase were searched for articles by the search terms 'malnutrition' and 'leptin'. The risk of bias was assessed by using JBI critical appraisal tools. Results were presented in tables and forest plots generated using STATA. A total of 16 articles were included. All articles included in the study are researching leptin, cortisol, or ghrelin, as well as cytokines. Forest plots were created for leptin, ghrelin, cortisol, Interleukin 10 (IL-10) and Interferon gamma (IFN-γ). Leptin had an overall effect size of 3.01 (95% CI 0.51; 5.51), ghrelin had an overall effect size of -1.71 (-2.97, -0.45), cortisol had an overall effect size of -1.16 (-1.49, -0.83), IL-10 had an overall effect size of -0.34 (95% CI -0.54; -0.14) and IFN-γ had an overall effect size of -0.02 (95% CI -0.25; 0.22), respectively. Our data revealed a decrease in leptin levels and an increase in cortisol, ghrelin and IL-10 when compared with control. This review displayed a relationship between leptin, cortisol, ghrelin and thymus atrophy. The change in T-helper cells contributes to the increased thymocyte depletion seen when severely malnourished. Leptin cannot explain all the changes observed, but may give insight into how it is a contributing factor in the changes the thymus undergoes.

Characterizing the immune response and pathogen tissue dissemination during progressive Treponema pallidum (T. pallidum) infection in the human is crucial for comprehending syphilis but it remains poorly understood, due to the unethical nature of inoculating volunteers with T. pallidum. An urgent new model is needed to study this issue. A human haematopoietic stem cell (Hu-HSC) mice model of syphilis was constructed through inoculation with T. pallidum. Blood and tissue samples were collected at serial time points (0, 3, 7, 14, 28 and 42 days post-infection) to analyse changes in the immune response and the presence of T. pallidum polA DNA and mRNA in the Hu-HSC mice. Treponema pallidum increased the percentage of helper T cell (Th) 1 and Th2 cells and induced the expression of Th1 and Th2 cytokines in the Hu-HSC mice, with a pattern of increasing and then decreasing response. However, there were no significant changes in the percentage of Th17 and Treg cells. Treponema pallidum polA DNA was detected in various organs such as the liver and spleen, indicating the dissemination of T. pallidum in the tissues. Furthermore, these organs were found to maintain the activity of T. pallidum through the detection of T. pallidum polA mRNA. These results suggested that Treponema pallidum induced the Th1 and Th2 immune response and disseminated in tissues in Hu-HSC mice. This study can provide a basis for future in vivo research on syphilis using the Hu-HSC mouse model and offer new references for explaining the pathogenesis of human syphilis.

Aplastic Anaemia (AA) is a rare, life-threatening condition characterised by bone marrow failure and pancytopenia. The primary treatment options include haematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST), each with distinct advantages and limitations. While HSCT offers a potential cure, its use is limited by factors such as donor availability, graft-versus-host disease, and its unsuitability for older patients. In contrast, IST is less invasive and more widely accessible, with a success rate of 60%-90%, but it carries a high risk of relapse and progression to myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML) and clonal evolution. Predictive markers are crucial for personalising treatment, monitoring efficacy and assessing relapse risk. However, only a few markers are currently implemented in clinical decision-making. This review focuses on the clinical, immunological and genetic markers, including cytokine levels, telomere length and paroxysmal nocturnal haemoglobinuria (PNH) clone size, which have been identified as potential predictors of IST response in AA. Most studies have been retrospective in nature, with variability in techniques and therapies, leading to inconsistency and limited reproducibility. Future large-scale prospective studies, conducted with standardised protocols, are essential to validate these markers. The development of a robust scoring system that integrates clinical and molecular data holds promise for improving personalised treatment approaches, ultimately enhancing AA management and patient outcomes.