The genotype frequency of human leukocyte antigen-G (HLA-G)+3142 C>G is higher among patients with sickle cell disease (SCD) who develop antibodies against antigens from blood group systems other than the Rh and Kell, according to a new study published in Transfusion and Apheresis Science.

“This highlights a possible role played by the HLA-G molecule in the [red blood cell] alloimmunization process,” the authors wrote. Alloimmunization is a common complication following blood transfusion in patients with SCD.

Here, a team of researchers from Brazil led by Carla L. Dinardo, MD, PhD, investigated whether the HLA-G+3142 C>G and 14-bp Ins/Del variations may be associated with the development of autoantibodies against red blood cells in patients with SCD. (HLA-G is associated with a number of inflammatory and autoimmune diseases).

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They conducted a single-center study on 213 patients with SCD. Of these, 110 were alloimmunized while the rest were not. The researchers divided the patients who were alloimmunized into 2 groups depending on the presence of antibodies against the Rh and Kell blood groups only or the presence of antibodies against antigens of the other blood groups too.

They found that patients who were alloimmunized and those who were not were statistically significantly different in terms of HLA-G+14 bp Ins/Del and +3142 C>G genotypes.

On the other hand, the frequency of the HLA-G+3142GG genotype was almost twice as common in patients who had antibodies against Rh and Kell blood groups only compared to those with antibodies against less immunogenic antigens.

The researchers concluded that the HLA-G molecule may play an important role in the alloimmunization process against red blood cells.


Martins JO, Pagani F, Dezan MR, et al. Impact of HLA-G +3142C>G on the development of antibodies to blood group systems other than the Rh and Kell among sensitized patients with sickle cell disease. Transfus Apher Sci. Published online April 27, 2022. doi:10.1016/j.transci.2022.103447