Precision alloimmunity: immunogenetics, antibody-mediated mechanisms, and translational strategies in transfusion and transplantation

Alloimmunity remains a formidable challenge in the domains of organ and hematopoietic stem cell transplantation, as well as transfusion medicine. The intricacies of alloantibody responses, shaped by immunogenetic variation, molecular recognition events, and cellular immune pathways, continue to threaten graft and transfusion outcomes despite decades of research and clinical innovation. Recent advances have uncovered not only the significance of major histocompatibility complex (MHC) diversity but also the important roles played by non-HLA polymorphisms and red blood cell antigen systems in mediating allogeneic responses. Powerful diagnostic technologies, deeper mechanistic insight into complement and Fc-mediated pathways, and emerging biomarker strategies have led to a more nuanced, yet still incomplete understanding of the mechanisms underlying antibody-mediated rejection and transfusion-associated alloimmunization. These developments underscore the persistent interplay between immunogenetic factors, alloantibody specificity, and the effector functions that drive clinical outcomes, while highlighting gaps in our ability to translate discoveries into personalized preventive and therapeutic approaches.

This Research Topic aims to advance the comprehensive understanding of alloimmune mechanisms across transfusion and transplantation settings, with a focus on precision approaches to risk stratification, prevention, and intervention. The primary objectives are to elucidate how immunogenetic diversity influences alloantibody generation and function; to clarify the molecular and cellular bases of antibody-mediated rejection and alloimmunization; and to integrate mechanistic discoveries with clinical strategies that enhance donor–recipient compatibility, immune monitoring, and therapeutic targeting. We encourage the formulation and testing of hypotheses that connect immunogenetic and immunologic findings with innovations in clinical management, tolerance promotion, and patient outcomes. This will foster translational progress, grounded in mechanistic insight, to improve long-term graft survival and transfusion compatibility.

This Research Topic welcomes original research articles, mechanistic studies, translational investigations, and comprehensive reviews that provide in-depth analysis of alloimmunity and its clinical ramifications. Purely descriptive, computational, or disease-specific studies without clear relevance to alloimmune mechanisms or clinical outcomes will not be considered. To further the field, we invite submissions on the following themes:

-Immunogenetic determinants of alloreactivity, including HLA and non-HLA variation
-Molecular and cellular mechanisms of antibody-mediated rejection in solid organ and stem cell transplantation
-Mechanisms and prevention of transfusion-associated alloimmunization, with a focus on red blood cell genotyping
-Advances in the detection and functional characterization of alloantibodies and immune monitoring
-Mechanistic and translational studies of tolerance-promoting or immune-modulating interventions
-Integrative biomarker approaches for early detection and risk prediction of alloimmune injury
-Translational models linking mechanistic discoveries to clinical application in donor selection and individualized immunosuppression

Article types considered for this Research Topic include original research articles, mechanistic studies, translational investigations, and comprehensive reviews.

The topic editors declare no conflict of interest

Article types and fees

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• ... View all formats

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Article types

This Research Topic accepts the following article types, unless otherwise specified in the Research Topic description:

• Brief Research Report
• Case Report
• Classification
• Clinical Trial
• Editorial
• FAIR² Data
• General Commentary
• Hypothesis and Theory
• Methods
• Mini Review
• Opinion
• Original Research
• Perspective
• Review
• Systematic Review
• Technology and Code

Keywords: Alloimmunity, Alloantibodies, Immunogenetics, HLA and non-HLA polymorphisms, Antibody-mediated rejection, Transfusion alloimmunization, Complement and Fc effector pathways, Immune monitoring and diagnostics, Biomarkers and risk stratification, Precision t

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.