Immune dysregulation disorders: understanding the overlap of autoinflammation, autoimmunity, and immunodeficiency

Immune dysregulation disorders comprise a heterogeneous group of conditions caused by genetic defects affecting proteins involved in innate and adaptive immune signalling, immune regulation and host defence. Advances in clinical genetics, molecular biology and functional immunology have transformed our understanding of these disorders, revealing that pathogenic variants affecting individual components of the immune system can result in diverse and overlapping clinical manifestations. Increasingly, it is recognised that many immune dysregulation disorders present with features spanning autoinflammation, autoimmunity and immunodeficiency, which may also be accompanied by lymphoproliferation, allergy or malignancy. These overlapping phenotypes challenge traditional disease classifications and highlight the complexity of immune regulation across different biological pathways.This Research Topic aims to explore the mechanisms, diagnosis, and management of immune dysregulation disorders that bridge the clinical boundaries between autoinflammation, autoimmunity and immunodeficiency. Despite major advances in genomic technologies and functional immune assessment, significant challenges remain in interpreting genetic variants, defining genotype–phenotype relationships, understanding variable disease expression and translating molecular discoveries into personalised approaches to patient care.A deeper understanding of how defects in immune regulatory mechanisms produce diverse clinical phenotypes will require integrating clinical observations, genetic data, molecular studies, and functional immunology. This Research Topic seeks to bring together basic scientists, clinical researchers and healthcare professionals across immunology, rheumatology, genetics and other relevant specialties to address these challenges. We particularly encourage studies that investigate novel disease mechanisms, improve diagnostic pathways, evaluate targeted therapies and advance precision medicine approaches across the lifespan.We welcome contributions addressing immune dysregulation disorders characterised by overlapping manifestations of autoinflammation, autoimmunity and immunodeficiency. Relevant themes include:• Clinical phenotyping of immune dysregulation disorders with overlapping autoinflammation, autoimmunity, immunodeficiency, lymphoproliferation and allergy. • Genotype–phenotype relationships, including variable expressivity, incomplete penetrance, somatic mosaicism and genetic modifiers. • Molecular mechanisms underpinning immune dysregulation, including innate and adaptive immune signalling, inflammasome biology, interferon signalling, immune tolerance and cytokine dysregulation. • Novel diagnostics, including genomic technologies, functional validation of genetic variants, biomarker discovery and innovative diagnostic approaches suitable for diverse healthcare settings. • Precision therapeutics, including targeted biological therapies, small-molecule therapies, gene-based therapies, treatment response and long-term clinical outcomes. • Real-world evidence, natural history studies, disease registries and longitudinal cohorts. • Global perspectives, including implementation of genomic medicine in resource-constrained settings, capacity building, international collaborative networks and approaches that improve equitable access to diagnosis and treatment. Submissions from geographically diverse populations, including low- and middle-income countries and resource-constrained settings, are strongly encouraged to improve understanding of global disease diversity, diagnostic challenges, and equitable access to precision immunology Topic editors: Samantha Cooray, Christian Klemann, Nobuo Kanazawa, Narendra Bagri Source: https://www.frontiersin.org/research-topics/86029/immune-dysregulation-disorders-understanding-the-overlap-of-autoinflammation-autoimmunity-and-immunodeficiency