Abstract Purpose Myasthenia gravis–associated myocarditis (MG-myocarditis) is a life-threatening condition. However, the immune dysregulation underlying its pathogenesis remains poorly defined. This study aimed to delineate the immunological pathways driving myocarditis development in patients with MG. Methods We performed integrated single-cell RNA sequencing and paired T cell receptor (TCR) repertoire profiling on peripheral blood mononuclear cells (PBMCs) from three patients with MG-myocarditis and four patients with MG-only. Analyses were conducted to characterize transcriptional states, differentiation trajectories, clonal expansions, and antigen-specific signatures associated with MG-myocarditis. Results Although the overall proportions of major PBMC lineages did not differ significantly between groups, transcriptomic profiling revealed substantial numbers of significantly differentially expressed genes across multiple immune cell subsets. Classical CD14+ monocytes displayed a marked skewing toward a pro-inflammatory differentiation trajectory, accompanied by downregulation of the activator protein-1-high intermediate state associated with anti-inflammatory programming. Within the T cell compartment, MG-myocarditis was characterized by robust expansion of TCR clonotypes concurrently enriched in CD8+ effector memory with high EOMES expression and CD8+ effector subsets, indicative of recent or ongoing antigen-driven activation. TCR–peptide binding prediction analysis showed preferential reactivity of these expanded clonotypes toward cardiac proteins—including titin, MYO10, and MYH6—implicating antigen-specific cytotoxicity in myocardial injury. In parallel, non-classical CD16+ monocytes and conventional dendritic cells (cDCs) exhibited enhanced antigen-presenting signatures, marked respectively by S100A8 upregulation and LY6E downregulation. Conclusion Our findings identify non-classical CD16+ monocytes and cDCs as potential cardiac antigen–presenting populations capable of priming pathogenic CD8+ T cell responses, thereby contributing to the immunopathogenesis of MG-associated myocarditis.
Abstract Sjögren disease is a chronic autoimmune disorder characterized by immune-mediated dysregulation that leads to exocrine gland destruction, impaired tissue repair, and frequent co-occurrence with other connective tissue diseases. Current internationally accepted diagnostic criteria rely predominantly on a combination of characteristic clinical manifestations, autoantibody profiles, and histopathological findings from minor salivary gland biopsy. In early-stage disease, when immune-driven glandular injury has not yet caused evident structural damage, or when histopathological alterations are delayed compared to clinical symptoms, the conventional “gold standard” method may produce false-negative outcomes, leading to diagnostic delays or overlooked diagnoses. In recent years, advances in multi-omics platforms, single-cell technologies, and artificial intelligence–driven data analysis have enabled the discovery of a growing number of promising biomarkers, including proteases, metabolites, microRNAs, and novel autoantibody epitopes detectable in serum, saliva, and tears. Several of these candidates have already undergone translational validation and are beginning to impact clinical decision-making. This review highlights recent advancements in biomarker research for Sjögren disease, evaluating their diagnostic utility, prognostic relevance, and therapeutic implications.
Abstract In the past 2 decades, two important conceptual advances that have contributed the modern immunological field are the establishment of immunometabolism as a discipline and the growing understanding of how immune systems can differ based on sex. Considering the well-known wide-ranging impact of sex on metabolic processes, these innovations would potentially be expected to be intricately linked. However, the majority of immunometabolism studies do not consider sex, or treat sex as a covariate that should be statistically adjusted for. Therefore, most studies interrogating how metabolic processes impact immune cell function may conceal how these processes are fundamentally different in males and females, and how they may shift in response to changing sex hormone levels across the lifespan. In this perspective, we argue that sex should be treated as a fundamental mechanistic input in immunometabolism, rather than solely as a statistical confounder or covariate, with direct consequences for how existing and new data are interpreted, and for how new therapies for immunometabolic health conditions are developed.
Abstract Biological aging profoundly influences immune function, yet its role in shaping immune remodeling within chronically inflamed tissues remains unclear. We investigated whether transcriptomic age identifies a plasmablast-associated immune aging pattern in IgG4-related disease (IgG4-RD). To address this question, bulk RNA sequencing was performed on submandibular gland lesions from 49 patients with IgG4-RD and 3 controls. Transcriptomic age (tAge) was estimated using a transcriptome-based aging model, and age acceleration was calculated as the residual from chronological age. Associations between age acceleration, immune transcriptional modules, and clinical characteristics were evaluated using Spearman correlation analyses. Transcriptomic age correlated with chronological age (ρ = 0.473, P< 0.001), whereas age acceleration was associated with serum IgG4 concentrations (ρ = 0.446, P = 0.001). Among immune transcriptional modules, the plasmablast signature showed the strongest positive association with age acceleration (ρ = 0.312, nominal P = 0.029), although this association did not remain significant after correction for multiple comparisons (FDR-adjusted P = 0.304). Germinal center B-cell and activated B-cell programs showed inverse trends. The plasmablast module also correlated with serum IgG4 levels. Together, these exploratory findings suggest a coordinated pattern linking transcriptomic age acceleration, plasmablast enrichment, and enhanced IgG4 responses. Rather than establishing a mechanistic pathway, these findings identify a candidate plasmablast-associated immune aging pattern that warrants validation in independent cohorts.
