An in vitro investigation of human antibodies to blood group antigens: Application for improved patient and blood donor management

Individuals exposed to a foreign and clinically significant red blood cell (RBC) surface structure, known as a blood group antigen, can be alloimmunised and produce an antibody. During pregnancy, mothers who are exposed to a foreign, paternally-inherited, blood group antigen on foetal RBCs can also be alloimmunised. The maternal antibodies destroys foetal RBCs in subsequent pregnancies and, if left untreated, results in foetal death. This is called haemolytic disease of the foetus and newborn (HDFN).

HDFN occurs most frequently in pregnancies where the mother is exposed to the paternally-inherited RhD blood group antigen on foetal RBCs. In 1967, licensing and introduction of a prophylactic antibody product, RhD- immunoglobulin, for all RhD-negative women, was one of the major medical advances of the 20th century. These RhD-immunoglobulin injections prevented the mother from alloimmunisation when exposed to the foetal RhD-positive RBCs. However, there are ongoing problems and challenges associated with RhD- immunoglobulin as it is sourced from blood donors who are deliberately injected with RhD-positive RBCs to produce anti-D antibodies and then, repeatedly injected to maintain “high anti-D levels”. Developing an alternative recombinant antibody source for RhD-immunoglobulin has been difficult as the mechanism of action of RhD-immunoglobulin is unclear. The first component of this study aims to investigate a potentially new mechanism of action and use phage display to capture the complexity of RhD-immunoglobulin. The second component of this study aims to apply phage display for a blood group antigen, other than RhD. Maternal antibodies recognising rare blood group antigens on foetal RBCs are not detected during routine testing and can result in a severe case of HDFN, such as the ATML blood group antigen in the Augustine blood group system. The antisera for typing this antigen is currently sourced from one individual. A recombinant antibody alternative will improve the availability of typing reagents for the ATML blood group antigen to aid in future cases of HDFN.

Lead investigator Dr Martina Jones
Associate investigator Prof Stephen Mahler
Postdoc/Associate investigator Dr Xuan Bui
PhD Student Eunike (Nysa) McGowan
Industry Partner ARCBS: Prof Robert Flower; A/Prof Catherine Hyland