In Focus
Blood group antigens with broad hemopoietic cell distribution
Challenges in naming of blood cell type-overlapping antigens
In immunohematology, a specific field of expertise is often focused on alloantibodies targeting a certain cell type, such as red blood cells (RBCs), platelets, or granulocytes. Recently, there has been an increased recognition of alloantibodies that react with antigens expressed by multiple blood cell types.
Although not a new issue, the awareness of these multi-cell type reactive antibodies appears to be increasing.
Antigens of the ABO blood group system are known to be present on RBCs and platelets, similar to the I antigen, which is also expressed by granulocytes. The presence of A or B antigens on platelets can affect platelet count increments following ABO-incompatible transfusions. In cases of fetal and neonatal alloimmune thrombocytopenia (FNAIT), cross-matching between maternal and paternal antigens and antibodies is influenced by these shared antigens.
Recent blood group discoveries have now increased this series of RBC antigens that are also expressed on other blood cells. For example, CD36, well-known on platelets (GPIV, NAK), and a well-established marker for RBC precursors during erythropoiesis, has recently been found in low amounts on mature RBCs. Rarely occurring antibodies against CD36 can cause FNAIT but also hemolytic disease of the fetus and newborn (HDFN) due to their reactivity with RBC precursors.
The genetic basis of the long-recognized RBC antigen Csa has recently been elucidated, revealing its expression on the CTL2 protein encoded by the SLC44A2 gene. This protein also carries the antigens VER, RIF and BROS. Notably, CTL2 is expressed on granulocytes, and carries the HNA3a/HNA3b antigens. The HNA3a/b polymorphism is identical to the Csa/Csb polymorphism, although conformational differences between CTL2 expressed by granulocytes and by RBCs may be present, which may cause variation in binding of anti-HNA3 or anti-Csa to respectively RBCs or granulocytes.
This new knowledge can be used in daily practice! For instance, detecting anti-CD36 antibodies using RBC agglutination methods is challenging due to low CD36 expression on RBCs. However, detection is more straightforward with platelet antibody assays. Laboratories already conducting HNA genotyping can efficiently genotype the Csa/Csb polymorphism as well.
Future discoveries of blood cell type-overlapping antigens necessitate careful naming to avoid confusion. The International Society of Blood Transfusion (ISBT) working parties, including Platelet Immunobiology, Granulocyte Immunobiology and Red Cell Immunogenetics and Blood Group Terminology, had a shared session at recent ISBT conference in Barcelona 2024 and are currently addressing these issues to develop solutions for consistent and clear antigen and allele naming.
