Erythrocyte antigens-surface structures capable of eliciting specific, humoral immune responses-were historically characterized by antibody-based methodologies, occasionally precluding accurate phenotyping and compatible blood transfusion.
Single-nucleotide variants (SNVs) code for most blood group antigens, although there are also many well-characterized indels, structural variants, copy number variants, or regulatory region variants.
Next Generation Sequencing (NGS) accurately calls SNV erythrocyte phenotypes. Adding long-, paired-end, and split reads and copy number analysis accurately calls more challenging blood group systems.
NGS aids analysis of challenging serologic cases, phenotypes without requiring blood samples, identifies rare blood donors and prevents alloimmunization via improved blood product matching.
Similarly, array technology advances allow rapid, inexpensive, and nearly exhaustive identification of known (and predicted) variants.
Red blood cell (RBC) antigens are inherited, intrinsic or adsorbed surface structures provoking specific humoral immune response. Historically, serologic—antibody-based and relatively unchanged since the early 20th century—assays imperfectly defined these antigens, at times hindering accurate phenotyping and compatible RBC transfusion and solid organ transplantation. Single-nucleotide variants (SNV), and less frequently structural variants, copy number variants or regulatory region variants encode RBC antigens. Whole genome, whole exome, and targeted next-generation sequencing (NGS) characterize these antigens more reliably and specifically than serology. Furthermore, long-reads, paired-end reads, split reads, and copy number analysis allow accurate prediction of challenging blood group systems including ABO, Rh, and MNS. NGS enriches analysis of challenging serologic cases by producing accurate phenotype data when blood samples are unobtainable, by screening the existing donor pool for rare blood identifying compatible blood for recipients via more rigorous standards and by preventing alloimmunization and hemolytic transfusion reactions. Similarly, recent array technology rapidly, accurately, inexpensively, and nearly exhaustively identifies known (and predicted) variants. Owing to significant time, cost, and clinical and research benefits, utilization of molecular RBC typing is expanding rapidly.
Red Blood Cell Antigen Phenotypes and Blood Groups
Red blood cell antigens
Red blood cell (RBC) antigens are inherited, polymorphic, intrinsic or adsorbed cell-surface protein or carbohydrate structures capable of eliciting a specific, humoral immune response ( Fig. 1 A ). RBC phenotyping, performed serologically with a spectrum of monoclonal reagents, deems antigens present on the RBC surfaces “positive” and those absent “negative”. Antigen variants include weak, el, mod, and partial antigens. Weak antigens are present lower in number than expected, while mod and el are present in such low numbers that sensitive serologic methods (ie, absorption-elution) must be used to identify them. Partial variants lack portions of the antigen structure and may produce alloantibodies targeting the absent portions.