Piezo1 is the carrier molecule for Er red cell antigens
When we think of blood groups, the familiar A, B, O, and AB categories, along with the Rh factor, often come to mind. However, the world of blood groups is far more complex and diverse than these primary types. In fact, the International Society of Blood Transfusion now recognizes 45 blood group systems comprising 360 red cell antigens. These antigens, which are present (or absent) on the surface of red blood cells, determine an individual’s blood group and can elicit immune responses if they are foreign to the body. A small number of red cell antigens, however, remain genetically uncharacterized and do not fall into any recognized blood group system. One such set of antigens, known as Er, awaited the revelation of its molecular basis for nearly 40 years since the discovery of its first member, Era.
In a study published in Blood in September 2022, Karamatic Crew et al. solved a long-standing enigma in red cell biology and elucidated the molecular and genetic basis of the Er antigens. Using a combination of cutting-edge techniques, including whole exome and Sanger sequencing, CRISPR/Cas9-mediated gene knockout, proteomics, extensive serological characterization, and the high-throughput automated patch clamp (SyncroPatch 384), the authors identified PIEZO1 as the genetic carrier of the Er antigens. The result is intriguing, especially considering that PIEZO1 is present at only a few hundred copies on the surface of the red cell, suggesting that low abundance does not hinder either functional significance or antigenicity.
Importantly, this study not only confirms the existence of the previously recognized Era, Erb, and Er3 antigens but also introduces two novel high-incidence antigens, Er4 and Er5. Antibodies against these newly identified Er4 and Er5 antigens have been linked to severe hemolytic disease of the fetus and newborn, a condition that poses significant risks during pregnancy.
In conclusion, demonstration of PIEZO1 as the carrier molecule for the long recognized Er red cell antigens establishes a new blood group system and further highlights the importance of this remarkable protein.
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Learn about a new automated high-throughput approach to studying PIEZO channels: https://www.nanion.de/news/a-new-automated-high-throughput-approach-to-studying-piezo-channels/