Two new and rare blood types identified

Almost a decade has passed since a new blood group protein has been identified, but an international team of researchers has recently discovered two transport proteins on red blood cells. Labeled as ABCB6 and ABCG2, they are responsible for the rare Langereis and Junior blood types, respectively, and bring the total number of identified blood type proteins to 32.

The antigens for the Junior and Langereis blood types have been known for decades, but it was not until Lionel Arnaud of the French National Institute of Blood Transfusion (INTS) and his colleagues tested the gene sequence of these proteins that they were able to confirm that mutations in ABCB6 and ABCG2 caused these blood types to be expressed.

Given the rarity of the Langereis and Junior blood types, hospitals do not often encounter individuals who fall into these categories when administering blood transfusions. Several ethnic populations who do have the Langereis and Junior blood types have been at risk for blood transfusion complications. For example, over 50,000 people of Japanese descent are believed to be Junior negative.

Individuals who are Junior-negative were found to be homozygous for the ABCG2 null mutations, while those who are Langereis-negative are homozygous for the ABCB6 null mutation. A null mutation may prevent the formation of a functional protein product.

In identifying the ABCB6 and ABCG2 proteins, researchers have brought on a host of benefits, both expected and unexpected. "The greatest implication is transfusion security. Langereis and Junior-negative persons are very rare and hence it is highly challenging to find them compatible blood when needed," Lionel Arnaud of the INTS in Paris wrote in an email to The News-Letter.

Arnaud imagines that his team's findings will come into effect relatively soon, meaning that all blood units could be screened for the Langereis and Junior types. Additionally, it will be easier and quicker to identify patients with these blood groups who may need transfusion or who may be donors.

"In transfusion medicine, time is life!" Arnaud wrote. The ability to match blood types for transfusion also has major implications in the body's acceptance of an organ transplant.

Another major and much more surprising outcome of this research is associated with anti-cancer drug resistance. ABCG2, a multi-drug transporter protein, not only specifies the Junior blood type, but is also the breast cancer resistance protein. It is known as such because of its possible disruption of drugs used in chemotherapy.

"It was a dream to target/inhibit ABCG2 during chemotherapy to improve it, but one didn't know whether its physiological roles, essentially in [the] intestine or bone marrow, are essential. We showed that more [than] 50,000 Japanese live very happily without expressing ABCG2," Arnaud wrote. This demonstrates that ABCG2 is nonessential and may be targeted pharmacologically in anticancer drug therapy.

The researchers also disproved many myths surrounding ABCB6, the porphyrin transporter gene and probable multidrug transporter that codes for the Langereis blood type. Scientists had previously thought that ABCB6 was important to hemoglobin production, but these experiments show that lack of ABCB6 is not fatal or related to anemia.

ABCB6 was also shown to exist beyond the mitochondria on the surface of hapatocellular cancer cells, which relates to its anti-cancer drug resistance. These more general results have implications for personalized medicine and anti-cancer drug resistance in the future.

There was another way in which this research was out of the ordinary. "Research is usually a competition between international teams, not an international collaboration as presented in the media. In our case, it was indeed an international collaboration," Arnaud wrote.

In fact, the research literally took place across the globe: researchers at Japanese Red Cross Blood Centers supplied the purified antibodies, Arnaud's team purified the matching proteins and later established the Langereis and Junior blood types' genetic bases, and Bryan Ballif of the University of Vermont used a mass spectrometer to identify the proteins.

Going forward, these international researchers will continue to search for more unknown blood types, estimating that there are still 10 to 15 that remain unidentified. Though these blood types are also rare, Arnaud argues that research of this kind can bring important results.

"It can be a waste of time to work on a ‘rare' blood type, but you don't think so when you have this rare blood type (for your transfusion security) or when researchers coincidentally found important information about anti-cancer therapy or personalized medicine."