BOMBAY BLOOD GROUP

Presenter: Dr. S. Udaya Bhaskar Rao, Ist yr PG Moderators: Dr. V. Vijay Sreedhar, Professor and HOD Dr.Shashikala, Assoc Prof

Bombay 'Oh': Man found to have rare blood group

TNN Jun 14, 2010, 04.01am IST

BANGALORE: One of the rarest blood groups has surfaced in the city a father who was donating blood to his son was found to be Bombay 'Oh' Phenotype. And BGS Global Hospital, which along with many other hospitals is observing World Blood Donor Day on Monday, added a new donor to its Rare Blood Group Registry. Called the Bombay Phenotype Group because the first such case was found in Bombay its incidence is 0.0004% of the global population

Introduction

Discovery made more than 50 years ago Detailed study of blood revealed a rare genotype (blood group) was neither A nor B nor AB nor O. Since the first case was detected in Mumbai (then Bombay), the blood group came to be called as Bombay Blood Group. Blood from a Bombay Blood Group individual only should be transfused to a Bombay Blood Group patient.

H antigen

precursor protein from which all blood groups are formed

A antigen (the blood group is then called A)

Absence of H antigen
Bombay Blood Group is termed as OH

B antigen (the blood group is then called B)

H antigen remains as H (the blood group is called O)

AB antigen
translates into both A and B Antigens (the blood group is then called AB)

How is it formed?

Figure 34-2 Synthesis of type 1 and type 2 chain H and AB antigens. Type 1 chain and type 2 chain precursors (underlined) are fucosylated by FUT1 and FUT2 fucosyltransferases to form H antigen. H antigen then serves as a substrate for A and B glycosyltransferases. The terminal carbohydrate epitopes denoting blood group H, A, and B antigens are highlighted in amber. Fuc = fucose; Gal = galactose; GalNAc = N-acetylgalactosamine; R = other oligosaccharide.

Fucosyltransferase type 1 (FUT1), the product of the H or FUT1 gene, catalyzes the formation of type 2 chain H antigen.

Inactivating

mutations in FUT1 are responsible for the Bombay and para-Bombay

phenotype .

H Deficient phenotypes
TYPE H deficient, non secretor(Bombay) H partially deficient, non secretor H-deficient ,secretor (Parabombay) Hm LADII NOTATION Oh O, Oh A, Oh B Oh +, Ah, B h Oho-secretor, Oh A -secretor, Oh B secretor OH m, AH m

I.RED CELL H-DEFICIENT, NON SECRETOR

In 1952,Bhende et al described the abnormal blood groups of three men from Bombay whose red cells were group O but H-negative. All had anti-H in their serum. This rare phenotype later became known as the Bombay or Oh phenotype

I. a)Serological characteristics

Not agglutinated by anti-H,A,B or AB. Typical Oh phenotype-No H,A or B antigen can be detected by adsorption and elution techniques. Atypical Oh phenotype-do bind anti H which can be detected in an eluate. It may also be possible to adsorb and eluate anti A and/or anti B from these cells.

I. b)Inheritance

Cappellini et al- inhibitor gene might be responsible Watkins and Morgan- H expression may be controlled by a gene at a locus independent from ABO and that the Bombay phenotype could arise from homozygosity for a rare allele, h, at this locus. Individuals homozygous for h may have A and/or B genes but these genes are not expressed as antigens on red cells or in secretions When describing the Bombay phenotypes the appropriate superscript may be added to the Oh notation when the ABO genotype is determined by family study, by glycosyltransferase analysis or by molecular genetical tests-Oh O, Oh A, Oh B, Oh AB. There is high level of consanguinity among parents of Oh individuals.

I. C) Glycosyltransferases

H transferase - not been detected in the serum or red cell membranes Oh sera and red cells contain A and B transferases when A and B genes are present. These enzymes are unable to act in the absence of their receptor substrate(H antigen) and neither A nor B structure is produced.

Oh red cells that have been made H active in vitro ,in the presence of H transferase , can be converted to A or B active cells by the appropriate A or B transferase.

I. D) Frequency and Distribution

Bombay blood group is very rare, but appears to be less rare in India than elsewhere. Bhatia and Sathe tested 167404 Indians in Bombay and obtained an Oh frequency of about 1 in 7600,an Oh frequency of 0.0115. Le pendu et al discovered a rich source of two types of H deficiency phenotype in Reunion island in the Indian ocean: typical Oh in the Tamoul Indian population and partial red cell H-deficiency , non secretor in the population of European origin. Oh found in following ethnic groups: People of European origin(predominantly atypical Oh) Japanese African Americans Sudanese family of Arab and black African extraction

1.
2. 3. 4.

II. Red cell H partially deficient, non secretor

Levine et al used the notation Ah to describe a phenotype in a non secretor Czech woman whose red cells lacked H but were weakly agglutinated by anti A.

The equivalent B phenotype B h , was found also in a Czech by Beranova et al. ABh has also been described.
Ah, Bh, ABh have mainly been reported in people of European origin.

II. A) Serological characteristics

The strength of A expression on red cells of some Ah individuals resembles weak A where as those of others are more like Ax, being agglutinated by only a minority of anti-A sera. B h red cells have weak B antigen. Little or no H antigen is detected on these cells. No H, A or B antigen is present in the saliva The serum contains anti H. Ah serum contains anti-B. In B h anti-A is always present and anti-B may also be detected. Reunion phenotype can be distinguished from Bombay phenotype by the quality of H on the cells.

II. C)Glycosyltransferases

Mulet et al and Schenken et al no H transferase in sera or red cell membrane from Ah or Bh individuals. Le Pendu et al detected very small amount of H transferase activity in sera from red cell H partially deficient ,non secretor individuals from reunion island. Ah and Bh sera contain A and B gene specified glycosyltransferases respectively. Red cell H partially deficient phenotypes arise from homozygosity for a mutant gene at the H(FUT1) locus, which produces only a very weakly active H transferase. Consequently the small amount of H structure produced is completely converted to A or B.

Red cells of people with another type of H deficiency have little or no III. cell deficient, secretor H,A and B antigens, yet Red they are ABHH secretors, with secretions containing normal quantities of H, A and B substances. The first family showing that people lacking H from their red cells could secrete H was observed by Solomon et al in 1965. 2 brothers, whose red cells lacked H and bound anti-A, but were not agglutinated by it, secreted A and H. A third brother with group O ,H negative red cells, secreted H alone.

A secretor of B and H with deficient red cells was subsequently found.

III. A) Serological characteristics

Red cells of Oh secretors are not agglutinated by most H antibodies, but they may be agglutinated weakly by the potent anti H in some Oh sera and by other strong anti-H reagents. Adsorption and elution of anti H may or may not reveal H antigen on the red cells of Oh-secretor. Oh-secretor red cells are not usually agglutinated by anti-A and anti-B but some OhA-secretor cells behave like Ax cells and are agglutinated by anti-A,-B and very potent anti-A. Similar variations exists with B antigen in OhB secretors. H substance is present in the saliva in approx normal quantities for an O secretor. A and B substances are detected in normal quantities in the secretions when A and B genes are present.\ The serum almost always contains an H like antibody , which is generally weak and reacts only at low temperature. This antibody called anti-HI, is not inhibited by secretor saliva and does not react with group O cord cells . rds of Oh-secretor from Hongkong had anti-HI or anti H active at 37c.

III. B)Glycosyltransferases

Originally no H transferase was detected in Oh-secretor sera or red cell membranes, although the appropriate A and B transferases were present. In four Oh-secretor sera, Le Pendu et al found H transferase activity representing about 5 -10% of that found in sera of people with normal H phenotypes and suggested that this enzym derived from secretory tissues

III. C) Frequency and distribution

H deficient secretors have been found in a diversity of ethnic groups and nationalities-Indian, European, Chinese, Japanese, South Eaat asian, Middle Eastern, Native american, Frequencies of 1 in 5000 in Thais, 1 in 8000 in Taiwanese and 1 in 15620 Hongkong chinese have been estimated

IV. Other H- deficient phenotypes-A)Hm

The primary characteristic of Hm phenotype is it dominant mode of inheritance, the rare phenotype appears in several generations of the same family. Hrubisko reported 3 Czech families with the Hm phenotype and several other families have been described since.

The H deficiency is not as dramatic as in Bombay ar Para Bombay phenotypes; Hm red cells are weakly agglutinated by anti-H.
The saliva contains normal quantities of H substance and H transferase I present in serum anr red cell membranes. Salmon et al suggest that the H deficiency in Hm must be caused by a dominant genetic defect unrelated to the H locus because of the presence of normal H transferase in serum and red cell membranes.

IV.B) Leucocyte adhesion defect type II

LAD type II has been diagnosed in 5 patients -4 Arab children and 1turkish LAD type II is a generalised fucosylation defect associated with recurrent infections, short stature, mental retardation and a distinctive facial appearance but also with H-deficient(Bombay phenotype) red cells, ABH non secretion. The LAD results from a deficiency of sialyl-Lex, a fucosylated ligand for E and P selectins. The likely explanation for the generalized fucosylation deficiency in the Arab children is a defect in the biosynthesis of GDP-L-Fructose , the donor substrate for fucosyltransferase from GDP-D-mannose. In the turkish patient GDP-fucose import into the golgi was proposed as a possible explanation