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Genetic of the ABO blood system and its link with the immune system

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Abstract

In the book "Eat Right For Your Type" the author Peter J. D'Adamo writes that the O blood type was the first blood type to appear in humans and affirms that the blood groups are the key to the immune system. Some recent phylogenetic network studies in humans and non-human primates implies that the A gene represents an ancient form of the ABO genes. Relationships between blood groups and infectious and noninfectious diseases and immunodeficiency abnormalities have also been reported in the literature. As D'Adamo's propositions seem to be in opposition with the current knowledge, we present in this paper some comments about the genetics and the evolution of the ABO blood group genes and some links between this blood system and the functioning of the immune system.
Rev. bras. hematol. hemoter. 2004;26 (1):60-63 Artigo Educacional
60
Artigo educacional / Educational article
Genetic of the ABO blood system and its link with the immune system
A genética do sistema ABO e sua relação com o sistema imune
Luiz C. de Mattos
1
Haroldo W. Moreira
2
1
Molecular Biology Department, Faculty of Medicine of São José do Rio Preto, SP.
2
Clinical Analysis Department, Faculty of Pharmaceutical Sciences, UNESP, Araraquara, SP.
Financial support: BAP Famerp (case 06336/00).
Correspondence to: Molecular Biology Department
Faculty of Medicine of São José do Rio Preto
Avenida Brigadeiro Faria Lima, 5416
15090-000 – São José do Rio Preto-SP – Brasil
Tel: 55 17 210-5700 / Fax: 55 17 227-6201 – e-mail: luiz.carlos@famerp.br
In the book “Eat Right For Your Type” the author Peter J. D’Adamo writes that
the O blood type was the first blood type to appear in humans and affirms that
the blood groups are the key to the immune system. Some recent phylogenetic
network studies in humans and non-human primates implies that the A gene
represents an ancient form of the ABO genes. Relationships between blood groups
and infectious and noninfectious diseases and immunodeficiency abnormalities
have also been reported in the literature. As D’Adamo’s propositions seem to be
in opposition with the current knowledge, we present in this paper some comments
about the genetics and the evolution of the ABO blood group genes and some
links between this blood system and the functioning of the immune system. Rev.
bras. hematol. hemoter. 2004;26 (1):60-63.
Key words: ABO system; genetics; polymorphism; immune system
Introduction
In 1997 the American naturopathic physician
Peter J. D’Adamo wrote a book entitled “Eat Right For
Your Type”
in which he presents a dietary program
based on the ABO blood types.
1
Also, the author explo-
res some aspects of the genetics and the evolution of
this blood system and affirms that the blood groups are
the key to the functioning of the immune system.
It is
not our intention to discuss here the supposed links
among ABO blood types to any dietary program.
Instead, we wish to present some comments about two
questions related to the genetics and evolution of the
ABO blood group genes and the links between this blood
system and the immune system according to current
knowledge, which are different to D’Adamo’s
propositions.
Was the O type the first blood type to appear in
humans?
Dr. D’ Adamo writes that the O blood type of the
ABO blood system was the first human blood type. The
ABO blood group system is a genetic trait determined by
genes occupying the ABO locus on chromosome 9
(9q34.1). This blood system is characterized by the
expression of two carbohydrate antigens (A and B)
expressed on the red blood cell membrane and in many
other tissues and two plasmatic antibodies (anti-A and
anti-B) that appear after birth. The synthesis of these
antigens is controlled by specific glycosyltransferases. The
A and B genes code to functional glycosyltransferases
capable of converting the H antigen precursor into A or
B antigens. The O gene codes to an anomalous
glycosyltransferase that is incapable of modifying the H
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Artigo Educacional Rev. bras. hematol. hemoter. 2004;26 (1):60-63
antigen. Independently, the synthesis of the red blood
cell H antigen is controlled by an a-2-L-fucosyltranferase
coded by the H gene (FUT-1) of the locus H located in
the chromosome 19 (19q13.3), from the precursor type 2
oligosaccharides (Galb1®4GluNAc). In individuals with
the secretor phenotype, the SE gene (FUT-2) codes to a
similar a-2-L-fucosyltransferase that is capable of
synthesizing the H antigen from the precursor of the type
1 oligosaccharide (Galb1®3GluNAc) in other tissues.
2
Therefore, the A, B, H and SE genes code to functional
glycosyltransferases but the O, h and se genes are
incapable of this.
In order to agree with the assertion that the O blood
type was the first human blood type to appear, it would
be necessary to admit that before humans, only the H
locus existed in non-human primates, but this does not
make any sense. Many papers were able to demonstrate
the presence of ABO antigens and the glycosyltransferases
responsible for the synthesis of the A antigen in tissues
and secretions collected from other non-human
primates.
3,4,5
Another possibility would be to accept that
the O gene evolved before the A and B genes in the ABO
locus. After constructing phylogenetic networks of human
and non-human ABO alleles, Saitou and Yamamoto
concluded that the A gene represents the ancestral form.
6
Thus, in the evolutionary sense, it is difficult to believe
that normal genes like A and B have evolved from
abnormal genes like O.
The three most common O genes identified in
different populations are O
1
, O
1v
(variant) and O
2
.
7-11
Compared to the ancestral form, the O
1
and O
1v
genes
have a deletion of a G base in exon 6 (guanine in position
261) and show additional nucleotide differences.
10
The
O
2
gene does not have the G deletion but has a substitution
(G802A) in exon 7, which appears to abolish its
function.
8,9
Although the O blood type is common in all
populations around the world,
12
there is no evidence that
the O gene represents the ancestral gene at the ABO locus.
Nor is it reasonable to suppose that a defective gene would
arise spontaneously and then evolve into normal genes.
Is the ABO blood system the key of the immune
system?
Dr. D’Adamo also asserts that the ABO blood group
system is the key to immune function. There are
interesting interactions among blood types and the
immune system. The blood types are characterized by
polymorphic antigens expressed in the red blood cell outer
membranes and in other tissues, similar to ABO.
2,13
Due
to immunogenicity, blood group antigens induce immune
responses following incompatible transfusions, during
pregnancy or after organ transplantation. Environmental
stimuli also contribute to the production of so-called “na-
tural antibodies”. Thus, a person can produce regular
and irregular antibodies specific to blood group antigens.
This feature represents a link between the blood groups
and immune function but is not the key to the immune
system.
2
The biological functions of blood group
polymorphisms are not completely understood but many
blood group antigens act as important molecules in the
cell-cell recognition involved in early embryonic tissue
differentiation and probably as a self declaration
mechanism in somatic cell communities.
2,14
There is also abundant evidence that blood groups
play a role in the susceptibility or resistance to various
infectious and non-infectious diseases.
15
One of the
arguments used to reinforce the role of these molecules
is the higher expression of the ABO carbohydrates in
secretions and tissues that have contact with the
environment such as in the skin and in mucous
membranes of respiratory and gastrointestinal tracts.
2
As
infectious processes are related to the attachment of
microbes to molecules expressed in host cells, probably
the ABO (and its associated genetic systems, Secretor
and Lewis) carbohydrate antigens evolved to create a
polymorphic profile in the mucous membrane. This is
important to alter potential receptors of bacteria, viruses,
etc.
16
Therefore, diversity of these antigens can be related
to the susceptibility or resistance to infectious diseases
and this feature also represents a functional relationship
between blood groups and the immune function. Experi-
mental evidence demonstrated the importance of the H
antigen, expressed in gastric mucous membrane, to the
attachment of Helicobacter pylori bacillus.
17,18
Some
epidemiological studies observed that the O blood group
is more common among individuals infected by this
pathogen.
19,20,21
Other papers also suggested that similar
mechanisms are implied in susceptibility of the Lewis
negative phenotype [Le(a-b-)] to the uro-pathogenic
Escherichia coli strain.
22,23,24
Despite these facts it is
difficult to believe that blood types represent the key to
the immune system. It is worthwhile remembering that a
small number of blood group systems express their
antigens in tissues other than hematopoietic tissue.
Rare null phenotypes were described in many blood
systems, some of which are associated with diseases, but
this is not a general rule. For example, carriers of McLeod
phenotype have a weak expression of Kell antigens and
do not express the Kx substance in their red blood cell
membrane. However, some phenotypes have an immune
dysfunction named X-linked chronic granulomatous
disease.
25
Carriers of Rh null syndrome, a hematological
disorder characterized by mild or moderate hemolytic ane-
mia, do not express Rh antigens in the red blood cell
membrane but this phenomenon is not related to immune
dysfunction.
26
Besides there is no evidence of any immune
Artigo Educacional.p65 07/05/2004, 14:2261
Rev. bras. hematol. hemoter. 2004;26 (1):60-63 Artigo Educacional
62
dysfunction among carriers of the Bombay phenotype, a
rare phenotype in which the A, B and H antigens are
absent, but the anti-A, anti-B and anti-H are expressed.
2
The immune system is a biological system that
evolved to discriminate self from non-self using a complex
network of T and B lymphocytes, antigen presenting cells,
cytokines, antigen receptors, antibodies, MHC restriction
and other cellular and molecular interactions. They is
important due to their ability to protect us against
intracellular and extra-cellular pathogenic micro-
organisms through cellular and humoral immune
responses.
27
Although there are links between the immune
system and blood group phenotypes, antibodies are
produced by the cells of the immune system and not by
the blood type loci. It is possible to detect the A and B
antigens in red blood cells and in secretions of newborn
babies but they do not express anti-A and anti-B antibodies
until several months of age. Possibly the influence of
environmental stimuli resulting from similar
carbohydrates expressed in microorganisms contributes
to the production of natural antibodies.
2,27
It is also
worthwhile to note that in the ABO blood group system,
the only system in which “regular antibodies” can be
detected, the specificities of anti-A, anti-B and anti-A,B
are necessary, but not sufficient to protect the body against
the higher antigen diversity present in the environment
and for normal immune function. Of course, the blood
type antigens and their specific antibodies are part of but
certainly not the key to the immune system.
Concluding remarks
The A, B, H and precursor oligosaccharides in many
mammalian species, in humans and non-human primates
as well as the glycosyltransferases responsible for their
synthesis have been well characterized at the biochemical
and molecular levels. The resulting knowledge can help
not only in the definition of an appropriated model to
explain the evolution and the biological importance of
the ABO blood system related to diseases, but also to
repudiate any absurd speculation without scientific base.
Finally, the complexities of the blood types and their
relationship with the functional aspects of the immune
system deserve much additional study. In the meantime,
D’Adamo’s speculations about the evolution of the ABO
blood types and the blood groups as the key to the immune
system appear to be fundamentally flawed.
Resumo
Peter J. D’Adamo, autor do livro “Eat Right For Your Type”,
escreve que o grupo O representa o primeiro tipo sangüíneo
que surgiu nos humanos e também afirma que os grupos
sangüíneos constituem as bases do sistema imune. Recentes
estudos filogenéticos realizados em primatas humanos e não
humanos estabeleceram que o gene A representa a forma an-
cestral dos genes que ocupam o locus ABO. Associações entre
os grupos sangüíneos ABO, doenças infecciosas, não infecci-
osas e imunodeficiências também foram relatadas. Diante das
proposições do autor, as quais se opõem às informações resul-
tantes de recentes estudos moleculares e filogenéticos, nossa
intenção é apresentar algumas reflexões sobre a genética e a
evolução dos genes do sistema ABO e as conexões deste siste-
ma com o sistema imune. Rev. bras. hematol. hemoter. 2004;26
(1):60-63.
Palavras-chave: Sistema ABO; genes ABO; sistema imune
References
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Avaliação:
Editor e dois revisores externos.
Conflito de interesse: não declarado
Recebido: 15/08/2003
Aceito após modificações: 01/09/2004
Artigo Educacional.p65 07/05/2004, 14:2263
... The immune system can distinguish between self and non-self. 9 Many cytokines, other molecules, and cells interact with a complex network for the immune system to function efficiently. The relationship between the ABO blood group and an immune response is well-established. ...
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