The HLA-DRB3 gene, part of the human leukocyte antigen (HLA) class II complex, encodes the β-chain of the HLA-DR heterodimer, which plays a critical role in antigen presentation to CD4+ T cells. HLA-DRB3 is distinct from the more common HLA-DRB1 and is primarily associated with the HLA-DR52 serological group. It is expressed in individuals carrying specific HLA-DR haplotypes, such as DRB1*03. *11. *13. and *14. Antibodies against HLA-DRB3 typically arise from allosensitization events, including blood transfusions, pregnancies, or prior organ/tissue transplants.
Clinically, HLA-DRB3 antibodies are implicated in transplant rejection, particularly in hematopoietic stem cell and solid organ transplantation. They can trigger immune-mediated damage by binding to donor HLA molecules, activating complement pathways, and promoting graft dysfunction. In transfusion medicine, these antibodies are associated with platelet refractoriness and transfusion-related acute lung injury (TRALI). Additionally, HLA-DRB3 has been studied in autoimmune contexts, such as rheumatoid arthritis and systemic lupus erythematosus, though its direct pathogenic role remains unclear.
Detection methods include solid-phase assays like Luminex-based single-antigen bead testing, which offers high sensitivity for identifying antibody specificities. Understanding HLA-DRB3 antibody profiles is critical for optimizing donor-recipient matching and managing post-transplant immunosuppression. Research continues to explore its immunogenicity, epitope-sharing patterns, and interactions with other HLA molecules to refine risk stratification and therapeutic strategies.