SCIENCE: Discovery of rare new blood type may save future newborn lives

The trag­ic loss of two sets of new­borns has pro­vid­ed impor­tant infor­ma­tion about a rare blood type that was first dis­cov­ered in humans 40 years ago.

Unrav­el­ing the mol­e­c­u­lar iden­ti­ty of a rel­a­tive­ly new blood group called the Er sys­tem may pre­vent such tragedies in the future.

“This study shows that even after all the research to date, sim­ple red blood cells can still sur­prise us,” says Ash Toye, a cell biol­o­gist at the Uni­ver­si­ty of Bristol.

Blood type describes the pres­ence or absence of com­bi­na­tions of pro­teins and sug­ars that coat the sur­face of red blood cells. Our bod­ies use these cell sur­face anti­gens as land­marks to dis­tin­guish self from harm­ful for­eign enemies.

The ABO blood group, which we are most famil­iar with, and the rhe­sus mon­key blood group are very impor­tant in trans­fu­sion com­pat­i­bil­i­ty. How­ev­er, in real­i­ty, there are dif­fer­ent blood group sys­tems based on a wide vari­ety of cell sur­face anti­gens and their variants.

Most of the most impor­tant ones were iden­ti­fied in the ear­ly 20th cen­tu­ry, but the last to arrive, called Er, hit our radar in 1982 and became the basis for the 44th blood group. Six years lat­er, a ver­sion called Erb was iden­ti­fied. Er3 was used as the code for the absence of Era and Erb.

Although the exis­tence of these blood cell anti­gens has been evi­dent for decades, lit­tle is known about their clin­i­cal impact.

When a blood cell appears with an anti­gen that our body has not clas­si­fied, the immune sys­tem acti­vates and sends anti­bod­ies to mark and destroy the cells with the sus­pect anti­gen. In some cas­es, fetal and mater­nal blood type mis­match­es can also cause prob­lems by sen­si­tiz­ing the moth­er’s immune sys­tem to for­eign anti­gens. Anti­bod­ies pro­duced at this time can cross the pla­cen­ta and cause hemolyt­ic dis­ease in the fetus.

For­tu­nate­ly, there are sev­er­al ways to pre­vent and treat hemolyt­ic dis­ease in new­borns today, includ­ing injec­tions for preg­nant moth­ers and blood trans­fu­sions for babies.

Unfor­tu­nate­ly, in some of the cas­es pre­sent­ed in this study, blood trans­fu­sions after cesare­an deliv­ery did not save the lives of the chil­dren, sug­gest­ing that there is some­thing that doc­tors and researchers are over­look­ing. It was done.

“We are work­ing on rare cas­es,” Nicole Thorn­ton, a serol­o­gist at the Nation­al Health Ser­vice Blood and Trans­plant (NHSBT) in the UK, told Wired. “It starts with the patient with the prob­lem you are try­ing to solve.

Such rare anti­bod­ies have been on the radar for many years, but their rar­i­ty has meant that they have remained poor­ly understood.

So Thorn­ton and col­leagues, led by NHSBT serol­o­gist Van­ja Kara­mat­ic Crew, test­ed the blood of 13 patients with sus­pect­ed anti­gens. As a result, five types of muta­tions, known as Era, Erb, Er3, and new­ly Er4 and Er5, were con­firmed in Er antigen.

By sequenc­ing the patien­t’s genes, they were able to iden­ti­fy the gene that encodes the cell sur­face pro­tein. Sur­pris­ing­ly, it was a gene already known to the med­ical com­mu­ni­ty. PIEZO1.

“Piezo­pro­teins are mechanosens­ing pro­teins that sense when red blood cells are com­pressed,” Toy­oi explains.

This gene is already asso­ci­at­ed with sev­er­al known dis­eases. Mice lack­ing the gene die before birth, and mice lack­ing the gene only in their red blood cells have hyper­hy­drat­ed and frag­ile blood cells.

Crew et al. con­firmed this find­ing by delet­ing PIEZO1 from a cell line of ery­thro­cyte pre­cur­sors, ery­thro­cytes, and test­ing for the pres­ence of the anti­gen. In fact, PIEZO1 is required for the uptake of the Er anti­gen to the cell surface.

This Er5 vari­ant is preva­lent in African pop­u­la­tions, sug­gest­ing that, like oth­er rare blood types found in Africa, it may have anti­malar­i­al properties.