IMMUNOHEMATOLOGY
relevance and media resonance
Editorial
Special Immunohematology Unit,
1
Immunohematology and Tranfusion
Medicine Complex Unit,Policlinico
Umberto I-Sapienza University,
Rome, Italy;
2
Department of Transfusion Medicine
and Hematology and Lombardy
Regional Rare Blood
Bank, IRCCS Ca’ Granda Ospedale
Maggiore Policlinico, Milan, Italy
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Correspondence: Serelina Coluzzi
e-mail: serelina.coluzzi@uniroma1.it
Blood Transfus 2022; 20: 441-442 DOI 10.2450/2022.0264-22
© SIMTIPRO Srl
A new blood group system: scientific
Serelina Coluzzi1, Nicoletta Revelli2, Barbara Baluce2
“Missense mutations in PIEZO1, encoding the Piezo1 mechanosensor protein, define
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the Er red blood cell antigens” prepublished by Thornton’s team in Blood, in September
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20221, is an excellent study showing that Piezo1, a protein of wide biological interest, is
the carrier of three known antigens that did not fit into any known blood group system.
Using a combination of cutting-edge DNA sequencing, gene-editing techniques and more
traditional approaches, researchers were able to answer questions that would have been
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impossible to answer not many years ago by identifying the molecular basis of five Er
blood group antigens, the recognized Era, Erb  and Er32-4 and two novel high-incidence Er
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antigens, Er4 and Er5. Thus, Er is the 44th blood group system to be discovered, 40 years
after the high incidence red blood cell Era antigen was first described. The study is the
first to describe different mutations of the antigen; due to a high level of polymorphism
of PIEZO1 it is likely that further antigens may be added to the Er system in the future.
Massive parallel sequencing will facilitate the recognition of new antigens and the
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determination of the frequency of different alleles in the population5.
The results of the study, also possible thanks to the fact that the team started their
investigation having historical blood samples from just 13 people gathered over 40 years,
will be officially ratified as defining a new blood group system at a next meeting of the
International Society of Blood Transfusion. Piezo1 is known to have important roles in
normal conditions and in multiple diseases (e.g., dehydrated hereditary stomatocytosis,
hereditary xerocytosis) and this research represents another new milestone in hematology
and in immunohematology6,7. The new discovery adds important knowledge for the
characterization of red blood cell immunization and it has been well received by the
scientific community; on the other hand we do not agree with reports in the newspapers
that compared the new system Er to the well-known, and most relevant for transfusion
medicine, ABO system. Lay press also gave too much emphasis to the Er system as the
most important one in the genesis of hemolytic disease of the fetus and newborn (HDFN).
Reported cases of Er alloimmunization are rare; however, the majority of Er antibodies
considered in Thornton’s study were identified during pregnancy, and anti-Er4 and
anti-Er5 were implicated in severe HDFN. HDFN, occurring when pregnant women
produce antibodies against fetal red cell antigens, affects 3/100,000 to 80/100,000
patients per year; it is a complex pathology, and several blood group systems must be
considered in relation to the immunogenicity of each of them8. Antibodies to the RhD
antigen are the most frequent causes of moderate to severe HDFN. IgG antibodies against
other Rh antigens (including c, e, C, E) and blood group antigens (including Fya and K)
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occur in about 0.5% of pregnancies9,10. The diagnosis and
management of HDFN today is based on serological tests
and imaging of the fetus. A new tool to diagnose maternal
immunization correctly can be useful for monitoring
pregnancies and hopefully for developing therapeutic or
prophylactic strategies. Discovering the genetic basis of
blood groups will allow scientists to develop new tests and
provide the best possible care even for patients with the
rarest of blood types, considering the prevalence, not yet
known, of antigen-negative individuals in populations
of different ethnicity. For example, in the future it could
become possible to select red blood cells for these antigens
to be used for diagnostic and transfusion purposes.
At present, the value of this discovery clashes with the
daily routine of the clinical tests to which pregnant women
are subjected: not all immunohematology laboratories
will be able to investigate this new system. Due to the
small number of patients with these variants, it will be
labor intensive to find commercial antisera or Er-negative
red blood cells able to investigate this group of antigens.
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This type of investigation will be possible in accredited
immunohematology reference laboratories, in which this
will be another antibody specificity to be considered in the
diagnosis of cases of HDFN in women with panreactive
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antibodies or in alloimmunized transfused recipients.
The Authors declare no conf licts of interest.
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No other use without premission
Coluzzi S et al
REFERENCES
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Missense mutations in PIEZO1, encoding the Piezo1 mechanosensor
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Blood Transfus 2022; 20: 441-442 DOI 10.2450/2022.0264-22