The molecular mysteries of human blood groups

Mercy Rophina

“Although our scientific understanding of the functions of blood is more sophisticated than ever, we remain in thrall to its primary mystique”

The elixir of human life

We all know that elixir is a liquid that will keep one young forever. There are multiple legends narrating the elixirs of human life. Have we ever wondered why can't our blood be that “elixir” ? Human blood has manifold functions and it is the one component which keeps us alive. Every known historical tale conveys two major beliefs about human blood,

• Loss of blood leads to death
• Blood can be used to cure illness

The history of human blood traces a long way back to the year 1492 where we find the very first reports of blood transfusion performed on Pope Innocent VII in Rome. This historical journey encompasses various landmark discoveries, successful scientific trails and fatal failures.

Blood and Beliefs

Recently, a British journalist Rose George in her book, “Nine Pints - A Journey through Money, Medicine and Mysteries of Blood” describes human blood to have two -faced nature. She explains this stating the fact that little did ancient people know about the biology of blood. According to them blood was something invisible, gets visible only when flowing from cuts, wounds, during childbirth, menstruation and miscarriage. This made blood “The symbol of life and death”. Interestingly, she makes a metaphoric comparison of this fact with the Greek mythological figure, Gorgon Medusa who was said to have two kinds of blood flowing through her veins - lethal blood in the left vein and life-giving blood in the right.

We are not the same - The blood difference

The fact that human blood differed from one individual to another was never until 1900 when Karl Landsteiner, an Austrian pathologist and immunologist made a landmark discovery in the University of Vienna. While working on his experiments using blood and serum samples of his workers he noticed something new which he stated as follows,

“I have recently observed and stated that the serum of normal people is capable of clumping the red cells of other healthy individuals”

This marked the identification of 2 major human blood group antigens namely A and B. With the results of his preliminary analyses Landsteiner reported that every human can be systematically categorized into A or B blood type based on the antigen expressed on their RBCs.

Determinants of difference

Human blood groups are decided by the presence or absence of antigens that are expressed on the surface of their RBCs. These markers are generally termed as Red cell antigens or blood group antigens. Blood type generally represents the complete set of red cell/platelet surface antigens carried by an individual. If a person has A and D antigens he/she would possess A+ve blood group and if he/she lacks both A and B antigens then they are termed to have O blood group. So basically, finding a blood donor match means that they are searching for a person who has the same type of antigens in his/her RBCs like the patient. But it is not all about blood groups.Any mismatch or incompatibility between these antigens during transfusion procedures or pregnancies can lead to severe immune responses which can sometimes bring life threatening complications.

Delving into the perpetual mystery

The problem doesn't end here. Very shortly after Landsteiner’s discovery, in the mid 19th century when knowledge about ABO compatibility was very well established, a mother of a stillborn child was transfused with compatible units of blood from her husband. But to physicians' surprise she suffered severe immune reactions following the transfusion procedure. This incident marked the discovery of yet another major RBC antigen which differs among humans - The Rh factor.

Maybe a story from 2018, about Zainab Mughal, a toddler from South Florida would make things a bit more clear. This little girl was battling cancer and was in need of multiple transfusions when the doctors found that she had one of the rarest forms of blood in the world. Her RBCs were missing a common antigen called “Indian B (Inb)” which most people possess. This made Zainab to be able to receive blood only from people who also missed the same antigen. These donors would mostly belong to Indian, Iranian or Pakistani descent. This information subsequently sparked a global call for donors to help save this toddler.

But what is this lnb? Shouldn’t it be either A, B, AB, O or RhD? Here begins our story. Yes, It is not just the presence or absence of just A or B antigens but a lot more other “not so well known” antigens which form minor human blood group systems. And here starts the story of my research journey.

The hidden part of the iceberg

There are a total of 43 recognized blood group systems comprising 349 antigens. Of these ABO and Rh are the 2 major antigens routinely checked for pretransfusion compatibility owing to their severe consequences and level of awareness among the public. Genetic variations occurring in some handful of genes decides the presence or absence of these antigens on the surface of the RBCs.

“Little efforts make a huge difference !”

My research project aims to make those little efforts in bringing more awareness about these not so well known blood groups.

Mercy Rophina is a PhD candidate at the CSIR Institute of Genomics and Integrative Biology (CSIR-IGIB) and her research focusses on genomics of rare blood groups.