Genotyping Applications for Transplantation and Transfusion Management: The Emory Experience

Abstract

Current genotyping methodologies for transplantation and transfusion management employ multiplex systems that allow for the simultaneous detection of multiple human leukocyte antigens (HLA), human platelet antigens (HPA) and red blood cell (RBC) antigens. The development of high resolution molecular HLA typing has led to improved outcomes of unrelated hematopoietic stem cell transplants by better identifying suitable donors typed at the allele level for HLA-A, B, C, DRB1 and DQB1 antigens. In solid organ transplantation, the combination of high resolution HLA typing along with solid-phase antibody identification and the calculated PRA have shown to be of specific benefit to highly sensitized patients, and have resulted in significant reductions of incompatible crossmatches at the time of organ allocation. This database-driven combined HLA antigen/antibody testing has promoted the routine implementation of the virtual crossmatch, in which an electronic crossmatch is performed, and perhaps even obviates the need for a physical crossmatch. Additionally, DNA-based testing for RBC antigens provides as an alternative typing method that mitigates many of the limitations of hemagglutination-based phenotyping. Although there are many applications of RBC genotyping in various transfusion settings, it has arguably been most useful in the management of transfusion-dependent patients with sickle cell disease (SCD) and thalassemia to minimize alloimmunization. The availability of high-throughput RBC genotyping for both patients and large populations of donors, along with coordinated informatics systems to link patients’ antigen needs with available antigen-negative and/or rare blood-typed donors, offer promise toward improving the efficiency, reliability, and extent of RBC matching for this population.

Blood group antigen and phenotype prevalence in the Korean population compared to other ethnic populations and its association with RBC alloantibody frequency

“…High‐throughput genotyping methods could be assimilated into routine practice by performing genotyping of a subgroup of frequent transfusion recipients (Anstee, ; Fasano et al ., ). Recipient with haemoglobinopathies, chronic anaemia or with haematologic malignancies could benefit from blood antigen‐matched blood by extended RBC typing other than ABO and RhD.…”

“…High‐throughput genotyping methods perform the simultaneous identification of allelic variants for multiples samples that predict phenotypes of blood group antigens (Fasano et al ., ). Genotyping can be performed either by microarray on a chip (Goldman et al ., ; Finning et al ., ; Lopez et al ., ) or by next generation sequencing technologies (Liu et al ., ).…”

Identification of genetic biomarkers for alloimmunization in sickle cell disease

“…Statistical power of genetic association studies depends on the number of tested markers, the SNP frequency and effect size of the SNP. Our cohort is currently the largest SCD cohort in literature with a relatively large study population of 275 SCD patients with a reasonably large number of cases ( n = 145) (Hoppe et al , ; Tatari‐Calderone et al , ; Hanchard et al , ; Tatari‐Calderone et al , ; Fasano et al , ; Meinderts et al , ; Oliveira et al , ; Sippert et al , ). While this cohort was suitable to identify strong to moderate associations of SNPs with a reasonable frequency, weak associations may have been missed due to sample size.…”

Feasibility of autologous intraoperative blood collection and retransfusion in small children with complex congenital heart defects undergoing cardiopulmonary bypass

“…However, this concept is now changing since class I HLAs have been found on the surface of mature RBCs suggesting that RBCs may be an under‐recognized source of HLA exposure and alloimmunization . Recently, DNA‐based testing for RBC antigens, called RBC genotyping, has become a reality and holds promise for providing antigen‐matched RBC transfusions in high risk groups such as children with sickle cell disease or thalassemia . Many of our congenital heart disease patients, in particular those with single ventricular physiology, also represent as a high‐risk group in that they receive numerous transfusions over multiple surgeries and will often require cardiac transplantation.…”