hh,
or the Bombay blood group, is a rare
blood type. This blood
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological pr ...
was first discovered in
Bombay
Mumbai (, ; also known as Bombay — the official name until 1995) is the capital city of the Indian state of Maharashtra and the ''de facto'' financial centre of India. According to the United Nations, as of 2018, Mumbai is the second-m ...
by Dr. Y. M. Bhende in 1952. It is mostly found in the
Indian sub-continent (
India
India, officially the Republic of India (Hindi: ), is a country in South Asia. It is the seventh-largest country by area, the second-most populous country, and the most populous democracy in the world. Bounded by the Indian Ocean on the so ...
,
Bangladesh
Bangladesh (}, ), officially the People's Republic of Bangladesh, is a country in South Asia. It is the eighth-most populous country in the world, with a population exceeding 165 million people in an area of . Bangladesh is among the mos ...
,
Pakistan
Pakistan ( ur, ), officially the Islamic Republic of Pakistan ( ur, , label=none), is a country in South Asia. It is the world's fifth-most populous country, with a population of almost 243 million people, and has the world's second-lar ...
) and parts of
Iran
Iran, officially the Islamic Republic of Iran, and also called Persia, is a country located in Western Asia. It is bordered by Iraq and Turkey to the west, by Azerbaijan and Armenia to the northwest, by the Caspian Sea and Turkmeni ...
.
Problems with blood transfusion
The first person found to have the Bombay phenotype had a blood type that reacted to other blood types in a way never seen before. The serum contained
antibodies that attacked all
red blood cells of normal
ABO phenotypes. The red blood cells appeared to lack all of the ABO blood group antigens and to have an additional antigen that was previously unknown.
Individuals with the rare Bombay phenotype (hh) do not express
H antigen
H antigen can refer to one of various types of antigens having diverse biological functions. H antigen is located on the 19th chromosome in humans, and has a variety of functions and definitions as follows:
* Also known as substance H, H antigen ...
(also called substance H), the antigen which is present in blood group O. As a result, they cannot make
A antigen (also called substance A) or
B antigen (substance B) on their red blood cells, whatever alleles they may have of the A and B blood-group genes, because A antigen and B antigen are made from H antigen. For this reason people who have Bombay phenotype can donate red blood cells to any member of the ABO blood group system (unless some other blood factor gene, such as
Rh, is incompatible), but they cannot receive blood from any member of the ABO blood group system (which always contains one or more of A, B or H antigens), but only from other people who have Bombay phenotype.
Receiving blood that contains an antigen which has never been in the patient's own blood causes an immune reaction due to the immune system of a hypothetical receiver producing immunoglobulins against that antigen—in the case of a Bombay patient, not only against antigens A and B, but also against H antigen.
In order to avoid complications during a
blood transfusion
Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...
, it is very important to detect Bombay phenotype individuals, but the usual tests for ABO blood group system would show them as group O. Since anti-H
immunoglobulins
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
can activate the
complement cascade
The complement system, also known as complement cascade, is a part of the immune system that enhances (complements) the ability of antibodies and phagocytic cells to clear microbes and damaged cells from an organism, promote inflammation, and ...
, it will lead to the lysis of red blood cells while they are still in the circulation, provoking an
acute hemolytic transfusion reaction An acute hemolytic transfusion reaction (AHTR), also called immediate hemolytic transfusion reaction, is a life-threatening reaction to receiving a blood transfusion. AHTRs occur within 24 hours of the transfusion and can be triggered by a few milli ...
. This cannot be prevented unless those typing the blood and providing care are aware of the existence of the Bombay blood group and have the means to test for it.
Incidence
This very rare phenotype is generally present in about 0.0004% (about 4 per million) of the human population, though in some places such as
Mumbai
Mumbai (, ; also known as Bombay — List of renamed Indian cities and states#Maharashtra, the official name until 1995) is the capital city of the Indian States and union territories of India, state of Maharashtra and the ''de facto'' fin ...
(formerly Bombay) locals can have occurrences in as much as 0.01% (1 in 10,000) of inhabitants. Given that this condition is very rare, any person with this blood group who needs an urgent blood transfusion will probably be unable to get it, as no
blood bank
A blood bank is a center where blood gathered as a result of blood donation is stored and preserved for later use in blood transfusion. The term "blood bank" typically refers to a department of a hospital usually within a Clinical Pathology laborat ...
would have any in stock. Those anticipating the need for blood transfusion may bank blood for their own use, but this option is not available in cases of accidental injury. For example, by 2017 only one
Colombian person was known to have this phenotype, and blood had to be imported from
Brazil
Brazil ( pt, Brasil; ), officially the Federative Republic of Brazil (Portuguese: ), is the largest country in both South America and Latin America. At and with over 217 million people, Brazil is the world's fifth-largest country by area ...
for a transfusion.
Biochemistry
Biosynthesis of the H, A and B antigens involves a series of
enzyme
Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...
s (glycosyl transferases) that transfer
monosaccharides. The resulting antigens are
oligosaccharide
An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sug ...
chains, which are attached to
lipid
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids includ ...
s and
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s that are anchored in the red blood cell membrane. The function of the H antigen, apart from being an intermediate substrate in the synthesis of ABO blood group antigens, is not known, although it may be involved in
cell adhesion. People who lack the H antigen do not suffer from deleterious effects, and being H-deficient is only an issue if they need a blood transfusion, because they would need blood without the H antigen present on red blood cells.
The specificity of the H antigen is determined by the sequence of
oligosaccharide
An oligosaccharide (/ˌɑlɪgoʊˈsækəˌɹaɪd/; from the Greek ὀλίγος ''olígos'', "a few", and σάκχαρ ''sácchar'', "sugar") is a saccharide polymer containing a small number (typically two to ten) of monosaccharides (simple sug ...
s. More specifically, the minimum requirement for H antigenicity is the terminal disaccharide
fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
-
galactose
Galactose (, '' galacto-'' + ''-ose'', "milk sugar"), sometimes abbreviated Gal, is a monosaccharide sugar that is about as sweet as glucose, and about 65% as sweet as sucrose. It is an aldohexose and a C-4 epimer of glucose. A galactose molecu ...
, where the fucose has an alpha(1-2)linkage. This antigen is produced by a specific fucosyl transferase (
Galactoside 2-alpha-L-fucosyltransferase 2) that catalyzes the final step in the synthesis of the molecule. Depending upon a person's ABO blood type, the H antigen is converted into either the A antigen, B antigen, or both. If a person has group O blood, the H antigen remains unmodified. Therefore, the H antigen is present more in blood type O and less in blood type AB.
Two regions of the genome encode two enzymes with very similar substrate specificities: the H locus (
FUT1
Galactoside 2-alpha-L-fucosyltransferase 1 is an enzyme that in humans is encoded by the ''FUT1'' gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ...
) which encodes the Fucosyl transferase and the Se locus (
FUT2
Galactoside 2-alpha-L-fucosyltransferase 2 is an enzyme that in humans is encoded by the ''FUT2'' gene. It affects the secretor status of ABO antigens.
Approximately 20% of Caucasians are non-secretors due to the G428A (rs601338) and C571T (rs4 ...
) that instead indirectly encodes a soluble form of the H antigen, which is found in bodily secretions. Both genes are on chromosome 19 at q.13.3. — FUT1 and FUT2 are tightly linked, being only 35 kb apart. Because they are highly homologous, they are likely to have been the result of a gene duplication of a common gene ancestor.
The H locus contains four
exons that span more than 8 kb of genomic DNA. Both the Bombay and para-Bombay phenotypes are the result of point mutations in the FUT1 gene. At least one functioning copy of FUT1 needs to be present (H/H or H/h) for the H antigen to be produced on red blood cells. If both copies of FUT1 are inactive (h/h), the Bombay phenotype results. The classical Bombay phenotype is caused by a Tyr316Ter mutation in the coding region of FUT1. The mutation introduces a stop codon, leading to a truncated enzyme that lacks 50 amino acids at the C-terminal end, rendering the enzyme inactive. In Caucasians, the Bombay phenotype may be caused by a number of mutations. Likewise, a number of mutations have been reported to underlie the para-Bombay phenotype. The Se locus contains the FUT2 gene, which is expressed in secretory glands. Individuals who are "secretors" (Se/Se or Se/se) contain at least one copy of a functioning enzyme. They produce a soluble form of H antigen that is found in saliva and other bodily fluids. "Non-secretors" (se/se) do not produce soluble H antigen. The enzyme encoded by FUT2 is also involved in the synthesis of antigens of the Lewis blood group.
Genetics
Bombay phenotype occurs in individuals who have inherited two recessive alleles of the H gene (i.e. their genotype is hh). These individuals do not produce the H carbohydrate that is the precursor to the A and B antigens, meaning that individuals may possess alleles for either or both of the A and B alleles without being able to express them. Because both parents must carry this recessive allele to transmit this blood type to their children, the condition mainly occurs in small closed-off communities where there is a good chance of both parents of a child either being of Bombay type, or being heterozygous for the h allele and so carrying the Bombay characteristic as recessive. Other examples may include noble families, which are inbred due to custom rather than local genetic variety.
Hemolytic disease of the newborn
In theory, the maternal production of anti-H during pregnancy might cause hemolytic disease in a fetus who did not inherit the mother's Bombay phenotype. In practice, cases of HDN caused in this way have not been described. This may be possible due to the rarity of the Bombay phenotype but also because of the IgM produced by the immune system of the mother. Since IgMs are not transported across the microscopic placental blood vessels (like IgG are) they cannot reach the blood stream of the fetus to provoke the expected acute hemolytic reaction.
References
External links
Hhat
BGMUT Blood Group Antigen Gene Mutation Database at
NCBI
The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health (NIH). It is approved and funded by the government of the United States. The ...
,
NIH
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
RMIT UniversityThe Bombay, para-Bombay and other H deficiencies
BombayBloodGroup.Organ initiative to connect individuals who donate and who are in need of Bombay blood group.
Genetics of the Bombay Phenotypeknow more
{{DEFAULTSORT:Hh Antigen System
Blood antigen systems
Transfusion medicine
South Asia