Autoimmune diseases arise from the amplification of natural autoreactive immune clones in genetically susceptible individuals under the influence of environmental triggers, epigenetic modifications, and hormonal factors. They comprise a broad and heterogeneous group of disorders characterized by immune-mediated tissue injury and dysfunction. More than 80 autoimmune diseases have been identified, affecting nearly every organ system. Although these disorders exhibit distinct clinical phenotypes and tissue specificity, many share common clinical manifestations, autoantibody profiles, genetic susceptibility loci, epigenetic alterations, and immunopathogenic mechanisms. Alterations in the composition of the microbiome (dysbiosis) have also been implicated in the development and progression of several autoimmune diseases. Furthermore, aberrant B-cell activation, impaired regulatory T-cell function, dysregulated type I interferon signaling, and chronic tissue-specific immune responses contribute to disease pathogenesis. The management of systemic autoimmune diseases, including rheumatoid arthritis, systemic lupus erythematosus, Sjögren’s syndrome (autoimmune epithelitis), systemic sclerosis, Idiopathic inflammatory myopathies, mixed connective tissue disease, and systemic vasculitis, is increasingly guided by the nature and severity of clinical manifestations and the dominant immunopathological pathways rather than by traditional disease classifications alone. This review examines whether autoimmune diseases should be regarded as distinct clinical entities or as diverse manifestations of shared immunopathological processes. By analyzing common clinical features, autoantibody profiles, tissue-specific immune responses, environmental influences, genetic susceptibility, epigenetic regulation, and therapeutic approaches, we highlight both the unifying mechanisms and the distinguishing characteristics that shape autoimmune disease expression. Collectively, the available evidence supports the concept that autoimmune diseases represent a spectrum of interconnected disorders that share common pathogenic pathways while maintaining disease-specific patterns of tissue involvement.
BACKGROUND:Macrophage activation syndrome (MAS) is a rare but potentially life-threatening complication of juvenile dermatomyositis (JDM). Data on its clinical presentation, diagnosis, treatment, and outcomes remain limited. OBJECTIVE:To systematically review the literature on MAS occurring in patients with JDM. METHODS:A systematic search of PubMed and Embase was performed for studies published between 1997 and 2025 reporting JDM-associated MAS/hemophagocytic lymphohistiocytosis. Three reviewers independently screened studies according to PRISMA guidelines. Due to marked heterogeneity and the predominance of case reports, a qualitative synthesis was conducted. RESULTS:Twenty-eight studies, including 39 patients, were analyzed. MAS occurred within three months of JDM diagnosis in most cases and frequently presented at disease onset. Diagnostic approaches were highly heterogeneous, with reliance mainly on clinical judgment and inconsistent application of HLH-2004 criteria. Anti-MDA5 was the most frequently reported autoantibody, followed by anti-NXP2. Corticosteroids, cyclosporine, and intravenous immunoglobulins were the most commonly used therapies, while biologic and targeted agents were increasingly reported. Mortality remained substantial. CONCLUSIONS:MAS is an underrecognized early complication of JDM associated with significant morbidity and mortality. The absence of disease-specific diagnostic criteria and standardized therapeutic strategies represents a major unmet clinical need. SYSTEMATIC REVIEW REGISTRATION:Not registered.
Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) in childhood is a rare but severe condition associated with significant morbidity and treatment-related toxicity. Current therapies mainly rely on high-dose glucocorticoids and conventional immunosuppressants, which may cause substantial long-term adverse effects in pediatric patients. Advances in the understanding of AAV pathogenesis have identified the alternative complement pathway, particularly the C5a-C5a receptor axis, as a key driver of inflammation and vascular injury, leading to the development of complement-targeting therapies. While these agents have shown efficacy and steroid-sparing effects in adults, pediatric evidence remains limited to case reports and small case series. Available data suggest that complement inhibitors may represent a promising option for selected children with refractory disease, although concerns remain regarding dosing, long-term safety, and accessibility. This review summarizes current evidence, discusses unmet clinical needs, and highlights the need for collaborative pediatric studies and dedicated clinical trials.
Intestinal immunity is coordinated by the spatial organization and temporal regulation of immune cells within a complex, antigen-rich environment. In this review, we discuss the latest advances in our understanding of how these two fundamental dimensions together shape intestinal immune homeostasis. We first examine the temporal dynamics of intestinal immunity, ranging from prenatal immune development, early-life immune education, and differentiation established by maternal factors and dietary changes. We discuss recent discoveries identifying RORγt-expressing antigen-presenting cells as key regulators of oral tolerance, providing a mechanism for how transient developmental windows establish long-lasting immune homeostasis. We then explore the spatial organization of intestinal immune cells, from regional specialization along the length of the gastrointestinal tract to compartment-specific immune populations, as well as micro-niches revealed by emerging spatial technologies. We review specialized chemokine networks, cellular interactions, and the microenvironments that coordinate immune responses in distinct intestinal regions. As we face increasingly detailed spatiotemporal maps, the next challenge will be to translate all this information into mechanisms underpinning how immune niches are established and maintained to promote intestinal health.
