Immune mechanisms and precision management of aplastic anemia

Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome characterized by pancytopenia and a hypocellular marrow, most commonly caused by immune-mediated destruction of hematopoietic stem and progenitor cells. Although cytotoxic T-cell-mediated autoimmune attack is recognized as a central pathogenic mechanism, the roles of B cells, natural killer cells, macrophages, inflammatory mediators, and the bone marrow microenvironment remain incompletely understood. Immunosuppressive therapy (IST) with antithymocyte globulin and cyclosporine has improved outcomes, but a substantial proportion of patients fail to respond, while relapse and treatment-related complications remain important challenges. Recent advances in single-cell technologies, multi-omics profiling, immune repertoire analysis, and targeted immunomodulatory therapies are providing new insights into disease heterogeneity and creating opportunities to develop biomarker-guided approaches to diagnosis, risk stratification, and treatment. This Research Topic aims to integrate mechanistic and clinical research addressing the immune basis of AA and its implications for precision management. Key questions include: Which T-cell, B-cell, natural killer-cell, macrophage, or microenvironmental pathways drive disease initiation, severity, and treatment resistance? How do genetic and epigenetic factors, including somatic alterations in immune-regulatory pathways, influence disease susceptibility and progression? Can immune-cell profiles, molecular signatures, or multi-omics approaches identify reliable biomarkers for diagnosis, predict response to IST, and assess relapse risk? Which emerging immunomodulatory and targeted therapies—including JAK inhibitors, CD38-targeting antibodies, complement inhibitors, and thrombopoietin receptor agonists—may benefit patients with refractory or relapsed disease? How can treatment strategies be optimized for clinically distinct populations, including pediatric, elderly, and pregnant patients? This Research Topic will promote a more integrated understanding of AA and support the development of individualized diagnostic and therapeutic strategies. To gather further insights into the immune mechanisms, biomarker development, and precision management of AA, we welcome contributions addressing, but not limited to, the following themes:• T-cell, B-cell, natural killer-cell, macrophage, and bone marrow microenvironment pathways in AA;• Genetic and epigenetic determinants of immune dysregulation, including somatic mutations and HLA-related mechanisms;• Immune-cell signatures, molecular biomarkers, and multi-omics approaches for diagnosis, prognosis, and treatment-response monitoring;• Mechanisms of response, resistance, and relapse following IST;• Emerging immunomodulatory and targeted therapies for refractory or relapsed AA;• Treatment optimization in pediatric, elderly, and pregnancy-associated AA;• Long-term clinical outcomes, treatment-related complications, and quality of life. Topic editors: Guangsheng He, Jinsong Jia, Jun Ho Jang Source: https://www.frontiersin.org/research-topics/84927/immune-mechanisms-and-precision-management-of-aplastic-anemia