Download BLOOD TYPE WITH SUPPRESSION OF BLOOD GROUP

THK AMERICAN JOURNAL OF CLINICAL PATHOLOGY
Vol. 37, No. 6, pp. 579-583
June, 1962
Copyright © 1962 by The Williams & Wilkins Co.
Printedin U.S.A.
A FAMILY OF "BOMBAY" BLOOD TYPE WITH SUPPRESSION OF BLOOD
GROUP SUBSTANCE A,
CHARLES H. AUST, M.D., NARCISSA D. HOCKER, M.T. (ASCP) BB,
ZOETTA G. KELLER, M.T.(ASCP), AND J. L. ARBOGAST, M.D.
Departments of Pathology and Clinical Pathology, Indiana University School of Medicine,
Indianapolis, Indiana
In 1952 in Bombay, India, Bhende and
colleagues4 discovered an unusual blood
group in the ABO system. The red cells were
peculiar in that they were not agglutinated
by anti-A or by anti-B serums and, therefore, seemed to belong to group 0 , but unlike
all other group 0 bloods, the red blood cells
were not agglutinated by anti-H. The serums
contained not only the expected anti-A and
anti-B, but also anti-H of the same degree of
activity as anti-A and anti-B.
In 1955 Levine and associates11 reported
the genetic suppression of blood group B in
an American family in which 3 members were
of the Bombay phenotype Oh- This convenient symbol was designated by Levine
for persons with "Bombay" blood. In addition to the genetic suppression of blood
group B, there was also evidence of suppression of the secretor gene »Se and the H
antigen. In order to explain the phenomenon
of the "Bombay" blood, 2 hypothetical genes
were invoked, X and x. The former is very
common and the latter very rare, but gene x
in the homozygous state (xx) is responsible
for the suppression of blood group substance
B, the secretor gene Se and H antigen.
To our knowledge, prior to this report,
there were 29 published cases of group Oh
persons: 18 in India,2"4- 9- "•1S 2 in Ireland,14
2 in Germany,15 and 7 in the United States. 1 ' u
In 3 of the Indian cases4 and in 2 of the
American cases1, u there is a history of
consanguinity.
Received, June 7, 1961; revision received,
January 12, 1902; accepted for publication February 28, 19G2.
Dr. Aust is Resident-Instructor in Pathology
and Clinical Pathology and a Clinical Fellow of
The American Cancer Society. Miss Hooker is
Chief Blood Bank Technician, Miss Keller is
Blood Bank Technician, and Dr. Arbogast is Professor of Clinical Pathology and Director of Laboratories.
579
After the original report of blood group B
suppression by Levine and co-workers,11 it
was 6 years before the second and third examples of blood group suppression were reported. Hakim and colleagues9 reported 2
families with the Bombay phenotype Oh,
one in which there was suppression of blood
group B and another in which there was suppression of A or B, or both, but this could
not be determined by examination of the
family groups. In 1961 Aloysia and coworkers1 reported the suppression of blood
group A2 and the probable suppression of
blood group Ai in 2 families in which the
Bombay phenotype Oh occurred. It is the
authors' purpose in tins paper to report an
American family of Irish and AmericanIndian extraction with 4 members of Oh
phenotype, and to present evidence of the
first proved example of suppression of blood
group Ai in one of these persons.
T H E FAMILY
The propositus was discovered after
having been a blood donor at the Indiana
University Medical Center, Indianapolis,
Indiana. In routine compatibility testing in
a group of donors for a person with hemophilia who had had a severe hemorrhage, we
detected a donor presumably of group 0 ,
Rh-positive, whose serum contained atypical
agglutinins detected by means of the minor
cross-match. The donor's serum agglutinated
all random group 0 bloods tested, including
all cells of a reference panel. The blood was
identified as Bombay type, in which the
serum contained anti-H agglutinins, as well
as anti-A and anti-B. Because of the infrequency of this blood group, members of the
family were studied in an attempt to find
other examples of blood with phenotype Oh
and to determine which blood group was suppressed.
The family tree is depicted in Figure 1.
580
ATJST ET
Vol. 37
AL.
E-T-©
1
n
JZ
5
AAxx
4
O
1
Al
2
6
Oh
3
Aj
7
Ai
8
A!
4
Aj
9
O),
5
O
Ai
10
AX
6
O
11
Oh
7
O
12
O
8
O
13
Oh
9
14
A2
10
A2
11
O
12
Al
FIG. 1. Complete shading = homozygous for gene x; partial shading = heterozygous for gene x;
II-l and II-2 died in the newborn period; II-3 was killed in World War II; and III-9 died at 1 year
of age.
TABLE 1
ABO BLOOD GROUPS OF THE MEMBERS OF THE
"BOMBAY" FAMILY STUDIED
Red Blood Cells'
Patient
Serum*
Age
Blood
group
H sub- Anti-A Anti-B Anti-H
stance
y-
i-i
1-2
II-4
II-5
II-6
II-7
II-8
II-9
11-10
11-11
11-12
11-13
11-14
11-15
III-l
III-2
III-3
III-4
III-5
III-6
III-7
III-8
111-10
III-ll
'.11-12
63
60
31
30
34
27
22
24
15
39
53
37
39
41
14
6
2
7
23
21
18
12
9
15
7
A,
0
0
Ai
0h
A,
A,
oh
Ai
oh
0
0,,
A,
Ai
A,
A,
A,
Ai
0
0
0
0
A2
0
A,
+
+
+
+
+
+
+
+
0
0
0
0
+
0
+
0
+
+
+
+
+
+
+
+
+
+
+
+
+
0
0
+
+
0
+
+
+
0
0
0
t
t
t
+
+
+
+
t
+
t
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
t
t
t
+
+
+
+
t
+
t
0
0
0
0
+
0
0
+
0
+
0
+
0
0
0
0
0
0
0
0
0
0
0
0
0
* +, agglutination; 0, no agglutination.
t Insufficient quantity of blood obtained by
eans of fingerstick; test not performed.
There is no known consanguinity in the
matings of these generations, but the parents
of 1-2 were first cousins. The first generation,
I, originally lived in Tennessee, subsequently
migrated to southeastern Kentucky, and
moved to Elwood, Indiana, approximately
25 years ago. In the second generation there
were 12 persons, of whom 9 are living. One
male II-3 was killed in World War II, and
twin males II-l and II-2 died in the newborn
period. It is of interest that II-5 and 11-14
are siblings.
MATERIALS AND
METHODS
Samples of blood from the members of this
family were grouped by using commercially
prepared human anti-A and anti-B serums.
The presence or absence of the H substance
on the erythrocytes was determined by using
commercially prepared anti-H lectin (Ulex
europeus), chicken anti-H, and 5 Oh serums.
Lewis grouping was determined by use of
anti-Le a antiserum. The blood groups were
confirmed by the usual back-typing method.
The presence of anti-H was determined by
means of using normal group 0 cells with
group Oh cells as control. The secretor status
of members of the family was determined by
testing for inhibition of the anti-H lectin by
saliva. Additional tests established the Rh
types (D, C, E, c, e) and MN groups.
RESULTS
The ABO blood groups, the presence or
absence of H substance on the erythrocyte,
June 1962
and the presence of anti-A, anti-B, or anti-H
agglutinins in the serum of each person
tested, are listed in Table 1. The propositus,
II-9, is Oh in phenotype, as are II-6, 11-11,
and 11-13. The serums of these persons contain anti-A, anti-B, and anti-H and are recorded as 0 h in Table 1.
The CDE genotypes (most probable), the
MN blood groups, Lewis grouping, and the
secretor status for each person tested are
listed in Table 2. All persons with Oh phenotype are nonsecretors and Lea-positive.
In Table 3, the titrations of the serum
from persons with Oh phenotype reveal these
serums to be more reactive at 5 C. than at
room temperature. At room temperature, 2
of the 4 serums reacted more strongly with
blood group Ai and B cells than with A2 and
0 cells.
TABLE 2
RH, MN,
L E W I S G R O U P S , AND SECRETOR STATUS
OF T H E " B O M B A Y " F A M I L Y S T U D I E D
No. of
Patient
1-1
1-2
11-4
11-5
II-6
11-7
11-8
11-9
11-10
11-11
11-12
11-13
11-14
11-15
III-l
1II-2
1II-3
III-4
1II-5
111-6
III-7
III-8
111-10
III-l1
IH-12
581
"BOMBAY" BLOOD TYPE
Genotype*
cDE/cde
CDe/cde
cde/cde
KDE/CDE
cDE/cde
CDe/cDE
cde/cde
CDe/cDE
cDE/cde
CDe/cDE
CDe/cde
CDe/cde
CDe/cDE
cDE/cde
cDE/cDE
cDE/cDE
cDE/cDE
cDE/cDE
CDe/CDe
CDe/cde
CDc/cDE
cDE/cde
cDE/cde
cDE/cde
CDe/cDE
MN
Le"t
Secretion
of ABU
N
M
MN
N
MN
MN
MN
MN
MN
MN
MN
MN
MN
N
MN
N
MN
MN
N
M
MN
M
MN
N
MN
+
se
Se
Se
Se
se
Se
Se
se
se
se
se
se
Se
Se
Se
Se
Se
Se
se
se
se
se
Se
Se
se
0
0
0
+
0
0
+
+
+
+
+
0
0
0
0
0
0
X
+
+
+
0
0
+
* Most probable genotype,
t + , agglutination; 0, no agglutination.
| Insufficient q u a n t i t y of blood obtained by
means of fingerstiek; test not performed.
TABLE 3
S E R U M T I T R A T I O N S O F Ob P E R S O N S
No. of
Patient
II-G
II-9
11-11
11-13
A! Cell
R.T.*
8
64
32
2
Aj Cell
5 C. R.T.*
IG
250
128
8
4
16
8
4
B Cell
5 C. R.T.'
16
128
64
16
4
64
32
4
OCell
s c. R.T.* 5 C.
16
128
64
16
4
S
4
4
16
32
16
10
* R . T . , room temperature.
Titration with several anti-H serums of
red blood cells 1-2 (a known heterozygote
(Xx)), II-4, and normal group 0 cells revealed no consistent significant findings.
This was done in an attempt to detect a person who was heterozygous (Xx) for the suppressor gene. Attempts to elute high-titered
immune anti-A serum from the red blood
cells of 11-13, as well as II-6 and II-9, were
unsuccessful.
DISCUSSION
The parents, 1-1 and 1-2, of the propositus
are heterozygous for gene x. II-6, II-9,11-11,
and 11-13 are "Bombay" and have phenotype 0 h- They are homozygous (xx) for gene
x. Other members of generation II may be
heterozygous for gene x, but no method other
than family studies is available at this time
which will serologically detect it. Scoring by
titration to discover a person, other than the
parents (1-1 and 1-2), who is heterozygous
for gene x was unsuccessful.
All of the progeny from the mating of II-5,
whose blood group is Ai, and IJ-6, whose
blood group is 0 h, are of blood group Ai and
heterozygous for gene x. No suppression of
ABO antigens can be detected because the
blood groups of the children are the same as
that of the non-Bombay type mother. Inasmuch as the propositus has no progeny, an
opportunity for detection of suppression of a
blood group in this instance can not be
established at this time. In the mating of
11-11, whose blood group is Oh, and 11-12,
whose blood group is 0 , there is no evidence
of blood group suppression because the
parents and children are all of group O. In
the mating of 11-13, whose blood group is O i„
and 11-14, whose blood group is A2, one of
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ATJST ET
the progeny, 111-12, is of blood group Ai.
This is a situation which does not seem to
follow the Mendelian laws of heredity.
The interpretation of these results was
made possible because of the observations of
Levine and co-workers" with regard to gene
interaction and suppression of blood groups.
The only source for blood group Ai is the
maternal grandfather, 1-1. These facts present evidence for suppression of blood group
Ai in the red blood cells of 11-13, who has a
phenotype of Oh- In accordance with the
suggestion made by Levine and associates,12
the blood of 11-13 may be represented as
OhAi. By implication it may be assumed
that the 3 siblings are also OhAi.
After the discovery of the 3 original persons with the Bombay phenotype Oh,
Bhende and co-workers4 suggested that a
new rare allele at the ABO locus was the
most logical explanation for "Bombay"
blood within the classical framework of the
ABO groups. These findings were compatible
with the theory of Hirszfeld and Amzel,10 as
modified by Morgan and Watkins, 13 that
blood groups A, B, and 0 are formed by a
series of mutations from a basic H substance.
The blood of persons who are homozygous
for the completely mutated genes was given
a genotype of OnOc. These persons would
not have any H substance in their red cells
and, therefore, in order to agree with
Landsteiner's rule, their serums should contain anti-H agglutinins. Thus, serums of
these persons react with red blood cells of
group 0 bloods containing H substance.
Ceppellini and colleagues,6 after analyzing
the data from the first 3 cases reported by
Bhende and associates,4 anticipated that
some inhibition within the ABO blood groups
and the ABH secretor system would be responsible for the "Bombay" bloods. The
assumption was proved to be correct when
Levine and co-workers11 reported the observation of the first blood group suppression
involving group B, in addition to the suppression of the H antigen in the red blood
cells and secretion in saliva. All persons
studied thus far, who are of the phenotype
Oh, have proved to be nonsecretors of H
substance in their saliva and are L e ( a +
b - ) . In 1948 Grubb 7 indicated that all
L e ( a + b —) persons were nonsecretors of H
Vol. 37
AL.
and in 1951s that all Le(a— b + ) persons,
were secretors of H. Later, in 1960, Bianco
and colleagues5 confirmed that Lewis and
ABH secretor factors were properties of 2
separate inherited systems but interacted in
the phenotype.
In 1957 evidence of the Yy genes was
found by Weiner and co-workers.19 The suppressor genes (yy), when present in a homozygous state, prevent the full expression
of the A antigen in red blood cells, but had
no effect on the secretion of blood group substances H and A in the saliva.16 The genes
(yy) do not suppress the expression of II antigen on the red blood cells, and this rules out
the presence of the action of (yy) in the
family presented in this paper, inasmuch as
the 4 persons of Oh phenotype have anti-H
agglutinins in their serums.
Most examples of Bombay phenotype Oh
have been detected by means of the incompatibility in the minor cross-match when
blood is processed for transfusion. A donor
or recipient of Bombay phenotype is detected by reactions of its serum with group
0 red cells, as well as with group A and B red
cells. It should be emphasized that all serums
should be back-typed with cells of group 0
as a matter of good blood bank practice.
SUMMARY
1. This paper deals with the study of a
family in which 4 persons have "Bombay"
blood.
2. Evidence is presented for suppression
of group Ai on the red blood cells of 1 of
these persons. To the authors' knowledge,
this is the first proved case of suppression of
Ax.
3. The "Bombay" blood of 11-13 may be
represented as OhAi.
4. The mechanism of gene suppression is
reviewed.
5. Routine back-typing of all serums with
group 0 cells is emphasized as a necessity
for good blood bank practice.
6. The results of this study illustrate again
the importance of complete family studies,
which may reveal additional compatible
siblings or other relatives. With the cooperation of members of this family, the 4 Oh
persons were registered at the Central File
June 1962
583
"BOMBAY" BLOOD TYPE
for Rare Donors maintained by the American Association of Blood Banks.
SUMMARIO I N I N T E R L I N G U A
1. Iste communication concerne le studio
de un familia in que 4 individuos ha sanguine
"Bombay."
2. Es presentate observationes que indica
pro un de iste subjectos le complete suppression de substantia de gruppo sanguinee Ai
super le erythrocytes. Secundo le informationes del presente autor, isto es le prime
caso de un provate suppression de Ai.
3. Le sanguine "Bombay" de 11-13 pote
esser representate como OhAi.
4. Es presentate un revista del mechanismo del suppression de genes.
5. Es sublineate le necessitate, pro le routine de un efficace banca de sanguine, le
retro-typage de omne seros con cellulas de
gruppo 0 .
6. Le resultatos del presente studio illustra de novo le importantia de complete
studios familial, viste que tal studios off ere
le possibilitate del discoperta de compatibile
fraternos o consanguineos additional. Gratias al cooperativitate del presente familia,
le quatro subjectos Oh esseva matriculate in
le Archivos pro Donatores Rar que es
mantenite per Association American de
Bancas de Sanguine.
b a y " phenotype.
lished.
Vox Sang., t o be pub-
3. B H A T I A , H . M . , SANGHVI, L . D . , B K I D E , Y . G.,
AND JHALA, H . I . : Anti-H in two siblings in
an Indian family. J . Indian M . A., 25:
545-548, 1955.
4. B H E N D E , Y . M . , D E S H P A N D E , C. K., B H A T I A ,
H . M . , SANGER, R., R A C E , I t . R., M O R G A N ,
W. T . J . , AND W A T K I N S , W. M . : A " n e w "
blood-group character related to t h e ABO
system. Lancet, 1: 903-904, 1952.
5. B I A N C O , I., S I L V E S T R O N I , E . , L A W L E R , S. D . ,
M A R S H A L L , It., AND SINISCALCO, M . : F u r t h e r
contributions t o t h e study of Lewis a n d
secretor characters. Vox Sang., 6: 337-348,
1960.
G. C E P P E L L I N I , R., N A S S O , S., AND TECILAZICH,
F . : L a malattia emolitica del neonato.
Milan: I s t i t u t o sieroterapico milanese S.
Belfanti, 1952, p . 204.
7. G R U B B , R . : Correlation between Lewis blood
group a n d secretor character in man. N a ture, London, 162: 933, 1948.
8. G R U B B , I t . : Observations on the human group
system Lewis. Acta p a t h , et microbiol.
scandinav., 28: 61-81, 1951.
9. H A K I M , S. A., V Y A S , G. N . , SANGHVI, L . D . ,
AND BHATIA, H . M . : Eleven cases of "Bomb a y " phenotype in six families; suppression
of ABO antigen demonstrated in two families. Transfusion, 1: 218-222, 1961.
10. H I R S Z F E L D , L., AND AMZEI,, I t . : fitude sur les
pl6iades"isoz6riques" d u s a n g ; surl'h6rddit6
des plciades. Ann. Inst. Pasteur, 65: 386414, 1940.
11. L E V I N E , P . , R O B I N S O N , E . A., C E L A N O , M . ,
B R I G G S , O., AND F A L K I N B U R G , L . : Gene
interaction resulting in suppression of
blood group substance B . Blood, 10:
1100-1108, 1955.
12. L E V I N E , P . , U H L I R , M., and W H I T E , J . : A h ,
an incomplete suppression of A resembling
O h . Vox Sang., 6: 561-567, 1961.
13. M O R G A N , W. T . J . , AND W A T K I N S , W. M . : T h e
Acknowledgments. T h e authors arc indebted to
D r . Philip Levine, Director, Division of I m munohematology, Ortho Research Foundation,
R a r i t a n , New Jersey, for a supply of Lewis antiscrum and his many valuable suggestions and
comments, in preparing t h e manuscript.
We also wish to acknowledge with gratitude
the technical assistance of t h e staff of t h e Blood
Consultation Service of t h e Ortho Research
Foundation in identifying t h e propositus, especially J a n e A. White, M . T . (ASCP), who confirmed our findings.
The authors wish to thank Mr. James F . Glore,
D e p a r t m e n t of Medical Illustration, Indiana
University Medical Center, Indianapolis, Indiana, for t h e preparation of Figure 1.
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Unterdruckung nicht das Blutgruppenmerkmal B . betrifft. Ztschr. Immunitiitsforsch., 120: 288-293, 1960.
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"Bom-
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G.
W.
L.:
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antigen A.