Machine learning in lymphocyte and immune biomarker analysis for childhood thyroid diseases in ChinaYang, Li, Niu
et alBMC Pediatr (2025) 25 (1), 249
Abstract: This study aims to characterize and analyze the expression of representative biomarkers like lymphocytes and immune subsets in children with thyroid disorders. It also intends to develop and evaluate a machine learning model to predict if patients have thyroid disorders based on their clinical characteristics, ultimately providing insights to enhance the clinical guidelines for the pathogenesis of childhood thyroid disorders.This cross-sectional study conducted in China examined diagnosed cases to describe the characteristics and expression of lymphocyte and immune subsets as predicted by the model. The study included two groups of children: 139 who were hospitalized in the Department of Endocrinology and a control group consisting of 283 children who underwent routine health checks at the Department of Children Healthcare. Cases were classified into three groups based on diagnoses: Graves' disease (GD), Hashimoto's thyroiditis (HT), and hypothyroidism. By employing 11 readily obtainable serum biochemical indicators within three days of admission, the median concentrations and percentages of subset measurements were analyzed. Additionally, nine machine learning (ML) algorithms were utilized to construct prediction models. Various evaluation metrics, including the area under the receiver operating characteristic curve (AUC), were employed to compare predictive performance.GD cases had increased levels of CD3-CD19 + and CD3 + CD4 + T lymphocytes, and a higher CD4+/CD8 + ratio. In both GD and HT, the levels of complement C3c, IgA, and IgG were higher than those in the control group. HT cases also had an increasing percentage of CD3-CD16 + 56 + T lymphocytes. Most immune markers increased in hypothyroidism, except for some T lymphocyte percentages and the CD4+/CD8 + ratio. To reduce age-related bias, propensity score matching was used, yielding consistent results. Among the nine machine learning models evaluated, logistic regression showed the best performance, being useful in clinical practice.Specific lymphocytes with different biomarkers are positively correlated with autoimmune thyroid disease (AITD) in children. Complement proteins C3c and C4, along with IgG, IgA, IgM, and T/B cells, are significant in childhood thyroid diseases. Our best model can effectively distinguish these conditions, but to enhance accuracy, more detailed information such as clinical images might be needed.© 2025. The Author(s).
Cytolytic γδ T-cells and IFNγ-producing CD4-lymphocytes characterise the early response to MTBVAC tuberculosis vaccineFelgueres, Esteso, García-Jiménez
et alNPJ Vaccines (2025) 10 (1), 58
Abstract: Infection with Mycobacterium tuberculosis (Mtb) can produce a wide spectrum of clinical manifestations, ranging from active tuberculosis (TB) to asymptomatic latent infection. Although CD4 T-cells are key immune effectors to control TB, early after infection, the innate immune response must play a role in tackling the disease. Here, we performed in-depth analyses of the acute immune response to MTBVAC, a candidate vaccine engineered from Mtb with the aim of protecting adults from pulmonary TB disease, still a major global challenge. scRNA-seq shows expansion of CD4+ and cytotoxic γδ T-cells, data confirmed by flow cytometry. CD4 T-cells exhibited lower HLA-DR and higher L-selectin expression, compared to BCG-stimulation, indicating differential activation or dynamics. Importantly, MTBVAC-activated γδ T-cells had a unique cytotoxic CD16+GZMB+ phenotype, reminiscent of effector cells found in Mtb positive individuals controlling infection. IFN-γ and TNF-α were released in cultures, while IL-17A/F were almost undetectable.© 2025. The Author(s).
Causal relationship between 731 immune cell immunophenotypes and giant cell arteritis: a Mendelian randomisation studyLiu, Liu, Gao
et alClin Exp Rheumatol (2025)
Abstract: Giant cell arteritis (GCA) is the most common form of vasculitis among adults aged 50 and over, characterised by systemic inflammation and the potential for severe complications such as blindness and stroke. Despite its prevalence, the aetiology of GCA remains incompletely understood, with current treatments largely relying on corticosteroids, which carry significant side effects.Our study utilised a bilateral Mendelian randomisation (MR) approach to investigate the causal impact of immune cells on GCA. By analysing 731 immune cell phenotypes from genome-wide association studies (GWAS) data of 3,757 European individuals, we aimed to identify genetic variants as instrumental variables for immune cell traits, thereby elucidating their role in GCA susceptibility. To ensure a robust examination, we used various MR techniques, including the inverse-variance weighted (IVW) method, and carried out sensitivity analyses to assess the dependability of our findings.Forward MR analysis identified three immune traits with significant associations with GCA: a protective effect from the absolute count of monocytic myeloid-derived suppressor cells and increased risks associated with HLA DR expression on CD14+ CD16-, and CD14+ monocytes. The sensitivity analyses yielded results consistent with the main findings. The reverse MR analysis yielded no statistically significant results.The study advances our understanding of the immunological underpinnings of GCA, suggesting that specific immune cells significantly influence the disease's development. These insights pave the way for the exploration of new therapeutic targets that could offer more targeted and tolerable treatment options beyond the current reliance on corticosteroids. Further research is needed to validate these potential biomarkers and therapeutic targets in clinical settings.
Development and optimization of human T-cell leukemia virus-specific antibody-dependent cell-mediated cytotoxicity (ADCC) assay directed to the envelope proteinPise-Masison, Rahman, Masison
et alJ Virol (2025)
Abstract: An estimated 10-20 million people worldwide are infected with the deltaretrovirus human T-cell leukemia virus type 1 (HTLV-1). Although most infected individuals remain asymptomatic, some progress to develop the fatal and debilitating disease adult T-cell leukemia/lymphoma (ATLL) or HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) or develop a plethora of other inflammatory disorders. In addition, HTLV-1 infection is associated with immunosuppression and a shorter lifespan. Although a protective role for neutralizing antibodies has been suggested, the role of non-neutralizing antibody-dependent cell-mediated cytotoxicity (ADCC) remains unclear, largely because an assay to measure this response has not been established. Here, we developed a high-throughput flow cytometry-based assay system to measure HTLV-1 envelope-specific ADCC. We used a natural killer cell-resistant T-lymphoblastoid cell line stably expressing the green fluorescent protein GFP to construct a target cell line expressing HTLV-1 envelope protein and using monoclonal antibodies and plasma samples from HTLV-infected or uninfected individuals, validating the specificity and sensitivity of the assay. We detected high ADCC activity in samples from HTLV-1-infected humans. In the plasma of experimentally infected macaques, ADCC activity was measured and a correlation between ADCC activity and HTLV-1 envelope antibody titers was observed. Further, we observed a significant increase in ADCC titer over time; as HTLV-1 infection persists, a higher ADCC response is generated, potentially influencing disease outcome. ADCC titer in HTLV-1-infected macaques also positively correlated with FLT3LG, IL-17F, CD4+ T cells, and lymphocytes but negatively correlated with monocyte frequency and classical monocyte frequency. In conclusion, these findings detail the generation of a cell line that enabled development of an HTLV-specific ADCC assay, which can be employed in large clinical studies as well as research involving humans or non-human primates.IMPORTANCEThis approach measures human T-cell leukemia virus (HTLV)-specific envelope antibody-dependent cell-mediated cytotoxicity responses, provides a critical tool to investigate the role of envelope-specific binding antibodies in the immune control of HTLV infection and pathogenesis, and may help guide the development of both therapeutic and preventative vaccine approaches.
膜杰作
Star Staining
