New genetic marker is associated with protection from alloimmunization in sickle cell disease

Patients with sickle cell disease (SCD) are treated with blood transfusions. However, because often red blood cells from minor antigen mismatched donors are used, allo-immunisation occurs in a substantial proportion of SCD patients. Such allo-immunity both undermines treatment and may also contribute to clinical complications.

Researchers of the Phagocyte Lab of professor Timo Van den Berg have shown that a single nucleotide polymorphism within the gene encoding the immunoglobulin receptor FcγRIIc, known as FCGR2C.nc-ORF, is a protective genetic biomarker for allo-immunization in sickle cell disease patients. Of additional interest, FCGR2C.nc-ORF was particularly strongly associated with the lack of allo-immunity to the less immunogenic red cell antigens.

Genetic marker

Despite extended matching in the Netherlands, (i.e. beyond ABO) for the most immunogenic red cell antigens Rh and K is common, further prevention of allo-immunity and optimization of transfusion strategies is needed. For even more extensive matching the now discovered genetic marker will be very helpful to beforehand discriminate patients with high from those with a low risk for allo-immunisation.

These findings not only provide direct evidence for idea that genetic factors contribute to the risk for allo-immunisation in SCD patients, but can also be exploited for the development of a diagnostic test predicting allo-immunity in SCD. The research is published in Blood and was conducted in collaboration with Karin Fijnvandraat, Professor of Pediatric Hematology at AMC, and Francois Pirenne of the French Hôpital Henri Mondor, Créteil, Parijs.