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Transcript
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
Observations
By
ALAN
on
RICHARDSON
PH.D.,
JONES,
H.
FRED
the
New
M.B.,
ALLEN,
B.S.
OSENFIELD,
antibodies
transfusions.
blood
an
which
reacted
persons
bearing
at
antigen
who
the
persons
who
sons
of the
and
anti-c
It svas postulated
suggested
that
that these reactions
were due
the inheritance
of this antigen
of
genetic
anti-e
categories
respectively.
capable
with
such
test
CDe/CDe
Since
of developing
cells
from
a person
this
Dr.
cells
anti-f
persons
was
whose
w’ith
available
order
to
equal
with
cells
but
of
antigen
the
type
cells
all
0.05 ml.
the
and
Cc,
Sanger,2
mdi-
in
addition
to
anti-c
of type
laboratory
and
or
cDe
anti-c
when
or cde.
opportunity
im-
The
was
serum
t.akeis
to
From
Harvard
then
the
Submitted
serum
been
agglutinate
serum
was
cells
lacking
to
cells,
each
when
and
further
against
which
with
absorptions
carried
being
absorptions
out
were
cells
gave
agglutinated
agall
antigen.
separate
technics,
re-
His
serum
agglutinated
CDe/CDe
Coombs
antibody
this
four
aI)sorption
two
tested
indirect
immunized
year
period.
of 1:128.
It
subjected
of absorption
serum,
deliberately
during
a five
to an end-point
CDe/CDe
below,
for
by
accepted
of the
cells
2 minutes
gently
and
negative
at
made
against
result.s
Rh
saline-suspended
at
absorbed
Kr.
to be tested.
1000
r.p.m.
the
tube.
shaking
Boston,
and
was
mixed
mixture
was
the
presence
or
and
the
seruns
The
Department
of
with
incubated
absence
of
Pediatrics,
Mass.
for
pul)lication
in part
by Public Health
and Dr. P. Vogel made
with
ml.
of the
Laboratory,
Boston,
2, 1953;
0.05
suspension
Grouping
School,
June
anti-f
saline
centrifuged
Work supported
Dr. R. Rosenfield
to
Kr.
residual
determined
Blood
Medical
failed
albumin,
a
had
blood
cells
completeness
described
cent
was
cDE/cDE,
the
This
METHODS
of 1:32.
reactions
45 minutes,
AND
(cde)
negative
packed
CDe/cDE.
of a 2 per
type
e and
ensure
to a titer
agglutination
of
anti-c,
by saline,
to contain
shown
negative
original
familiar
cDE/cDE
are capable
of producing
persons
lack the f antigen,
they
are
a chromosome
in this
negative
Rh
of washed,
To
cells
was
In
the
2 hours.
CDe/cDE
was
Rh
remove
volumes
37 C. for
for
blood
injections
of
saline-suspended
containing
with
of Race
the
hypothesis.
Kr.,
In
to
and
such
MATERIALS
peated
glutinated
linked
to a new
w’as cie-
did not have
a chromosome
bearing
the gene combination
cc failed
f antigen
on their
cells. Typical
examples
of the Rh genotypes
of
lack the f antigen
are CDe/CDe,
cDE/cDE
and CDe/cDE.
Per-
potentially
munized
AND
certain
Rh types,
only blood
cells
of type
cde or cDe being
agglu-
termined
by a pair of allelic
genes
F and f tightly
Dd and Ee pairs.
In the data
of Rosenfield
et al., as well as in those
viduals
to
have
STEINBERG,
M.D.
DIAMOND,
M.D.
KRIETE,
with
bloods
of
one chromosome
least
by this antibody.
f. It was further
tinated
G.
ARTHUR
K.
LOUIS
Anti-f
Vogel,
Gibbel,
Sanger,
and Racet
recently
described
the
found
in the serum
of a hemophiliac
who had received
numerous
In addition
to anti-N,
anti-S,
and anti-K,
the serum
contained
antibody
from
Agglutinin
(LONDON),
I\I.D.,
JR.,
BERTRAND
R
Rh
Service
it possible
ours.
117
June
25,
Grant
for
1953.
H
1227.
us
to
compare
a specimen
of the
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
118
by
All
reactions
one
of us
follows:
as
RI!
NEW
first,
were
and
in
rea(ler
In
results
which
the
family
The
of 1)100(15
1)V the
knew
blind.
In- another.
a series
followed
the
read
read
AGGLUTININ
the
given
by
antiseruns
studies
results
results
ANTI-F
the
of the
obtained
with
anti-D,
anti-C,
was
l)eing
tubes
reactions
the
he
did
randomly
other
absorbed
anti-E,
used
were
of all
were
read
serum
were
read
Kr.
anti-c,
isot.
and
kiio’
numbered
bloods
anti-c.
vhich
Although
l)lOOd
was
being
tested.
H
1
Fully
.
Typed
Tests
Bloods
of the
bloods
absorbed
failed
lowing
tests
group
Since
techisics
residual
antibody,
be only
2.
Kr.
a selected
between
MNS,
P,
betw-een
s’as
w’ith
c-positive
CDe/ CI)e
shown
that
if it. s-ere
indeed
anti-f
the
panel
the
K,
Le,
the
of eleven
Kr.
antibody
Fy, atsd
Lu,
Kr.
atsd
antibody
three
mothers.
The
the
Rh
serum
associated
no
longer
with
the
to be made
(member
Nevertheless
type
of
the
by
example
the
the
4 must.
of the
serum.
possibility
that.
matings
of certain
factor,
chro-
anti-c.
indirect
could
CDe
The
there-
C Dc. cdE
d aistigen,
The
t.he
reactions
the
Family
w-ith
unknow’n
No. I
cDe
and
cells
these
antibody
Positive
Kr. Negative
cde
therefore
of this
mot.hers
fathers
with
in figure
an exact
cde
critical
1 the father
not have
d.
2 the genoI)d.
were
bloods
cdE/cde
1.
determination
heterozygous
individual
evidence
of the
and the
Two
bloods.
Thus
its family
DD and therefore
does
by the Kr. serum.
In family
agglut.iisated
be
critical
ant.i-d.
critical
homozygous
Kr.
CDe
CDe
of
of each of these
matings
is show-n
are of value
insofar
as they enable
studies
member
Kr.
ilsvolved
of the genotype
1) is undoubtedly
his cells s-ere
presence
cde
anti-c.
contained
Rh
typed
Chromosome
families
One
family
the
the serum
could
not contain
blood
by saline,
albumiis,
and
Family
studies.
Five
of the several
families
studied
provided
showing
that
t.he alst.ibody
iii the absorbed
Kr. serum
was not
five families
involved
matings
of CDe,cDe
fathers
with cde/cde
remaining
fully
and the folJk. However,
or ant.i-d.
and
Serum
ABO,
tests
had
against.
associatiois
associatioti
donor
careful
Coombs’
fore
an
the
Furthermore,
serum
any
systems:
suggested
mosome.
Kr.
to disclose
blood
these
ESULTS
not
Despite
agglutinated
enabled
tts to exclude
ant.i-d.
was
#{149}
0
Family
CDe
No. 2
CDe
cdE
IJ
cde
.
3’
CDe
FIG.
excluded
cde
1.-Examples
in
the
cDe
of
seruns
two
studied.
cde
families
CDe
providing
critical
cde
bloods
CDe
which
enable
cdE
anti-d
to
be
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
JONES,
TABLE
1.-The
Types.
The
STEINBERG,
Reactions
ALLEN,
of
Relationship
the
DIAMOND,
Absorbed
between
Serum
Kr.
the
AND
.4ntigen
with
and
the
119
KRIETE
Blood
Gene
of
Various
Combination
Rh
ce is
Demonstrated
Reactions
Probable
with
absorbed
Kr.
..
Positive
Gene
combination
cde/cde
present
Cde/cde
cc
t This
1
0
5
0
CDe/cde
32
3*
cDE/cde
10
0
2
0
0
20
0
10
0
3
CDe/CDe
CDe/cDE
Bloods
the
five
a discussion
genotype
selected)
At
for
is given
individuals.
colored
and
time
the
anti-R.h
data confirm
antigens.
least
one
.
bloods
described
by
3. Presence
It
has
Acting
and
anti-c
on
but
how
passing
sera
shown
has
not
by
in
with
a positive
of 121 unrelated
with
the
bloods
Kr.
reaction.
(but
absorbed
tested
of these
w-ere
not.
exceptional
absorbed
data
of
instances
in
this
serum;
serum.
determined
w-ith
of the
derived
from
persons
cc are agglutinated
Kr.
randomly
Kr.
are presented
in table
1.
Kr. serum
does not detect
any
foregoing
removal
Other
that the antibody
the anti-c
closely
the
know-n
having
by
at
this
which
CDe,,/cde
will be discussed
which
remains
resembles
the
in the
anti-f
anti-c
likely
Antisera
that
used
absorbed
three
times
they
of anti-c
we
since they
tested
for the
in
this
anti-c,
twice
w-ith
both
been
failed
to react
cDE/cDE
cells.
to react
With
detected
of anti-c.
the
view
After
with
cells
sera
are
from
cells and
the
this treatment
cells
of a second
of
the
w-ide
of the
individuals
or heterozygous
It is perhaps
existence
in
and
can be show-n to lack this antipresence
of aisti-f
in the anti-c
in homozygous
typical
of anti-f.
it is that
remarkable
laboratory.
with
CDe,/CDe
sera
continued
was
present
characteristics
examples
donors
of anti-f
w’as
previously
most
bloods
w-ere
three
the
suggested
and
anti-c
the cde chromosome
they showed
other
in
by
assumption
absorbed
of
to
routinely
absorption
fit
that
only bloods
the gene
combination
production
serum
was
removal
in
this
sera
The
to
et al.
been
the
anti-c
serum
for
Rosenfield
for
The
from the
complete
already
gen.
also
with
of Anti-f
candidates
likely
The results
the absorbed
is called
agglutinated
below.
It is apparent
Kr.
serum
after
most
phenotypes
show
chromosome
exceptions.
persons
Rh
sera.
that
They
Attention
were not
serum.
the
white
usual
The
as
these
of unrelated
same
Rh
of
0
.
cDe/cde
cDE/cDE
text
0
4
cdE/cde
Gene combination
ce not present
See
Negative
31
CDE/cdet
*
serum
genotype
anti-c
for
type
used
in whom
condition
and
pertinent
to tsote
antibody
range
in such
of reactivity
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
120
NEW
We also
plus anti-E
cDE.
tested
the
as a result
Since
far
been
the
cDE/cDE
the
cells
that
pothesis
tivity
cells
serum
against
in this
w-as
removed
anti-f
AGGLUTININ
ANTI-F
serum
from
a CDe/CDe
donor
of isoimmunization
of pregnancy
antigenic
found,
RH
not
case
w’ere
expected
to
all activity
was
not
cde/cde
from
cells
the
Had
present.
would
have
who had produced
by a fetus
of type
of a type
serum
anti-f
been
in which
contain
anti-f.
thus
been
anti-c
CDe/
f has
not
Absorption
strengthening
present
so
with
the
some
hy-
residual
ac-
expected.
DISCUSSION
R.osenfield
et
system.
After
new antibody
by
mined
the
our
anti-F
f was
data
cc
of Rosenfield
In
cDE,
cdE
or
at
routinely
anti-f.
detect
sary
the
with
When
from
be
hypotheses
to
be
for
claimed
of a “position
esis
would
the
antigen
sional
overlooked.
that
state
c do
with
red
genotype
of f when
c and
fail
CDe/CDe
contain
anti-f.
not
genes
in the
the
explanations,
e w-hich
the
si-hen
in
the
bloods
from
persons
such
as CDe,
did
presence
finding
not
carry
of anti-f
of such
excep-
of an individual
whose
genotype
The blood
of this person
would
that
this
as
serum
contained
CDe/cde.
In
order
or CDe/Cde
it is necesWe have shown
that such
individual
cde/cde
who
or cDe/cde
w-hich
would
consider
to that shown
clearly
similar
f is present
(as
precluded
bloods
; these
has
been
immunized
cells.
genetics
of the f antigen
the attractiveness
of a theory
of a fourth
pair of allelic
genes
must
not allow
other
Iis the present
st.ate of evidence,
equal validity
may
a hypothesis
absence
possible
For
serum
sera
a susceptible
hypothesis
of thirty-five
have
of type
does
than
rather
effect”3’
chromosomes
of
w-hich
new
cdeF.
out
chromosome
demonstrated
the
anti-c
the
of a serum
Kr.
opposite
the hypothetic
case
cells were f positive.
obtained
cells
we
of f in bloods
considering
the
the postulation
involving
and
an anti-c
be
may
CDe/cDE
c and
three
absorbed
anti-c
serum
because
of the fact
blood
w’ould be classified
mistakenly
presence
to employ
a serum
that
anti-c
the
the
the
deter-
was
of this
and
Rh
that
from persons
with the gene
confirming
the observations
1) that
by the
the
named
discovery
proof
cDEf
derived
thus
(table
time
fact
consider
whose
by our
Therefore
same
the
used
be agglutinated
to
the
CDef,
as
only in bloods
chromosomes,
agglutinated
the
However,
For example,
CDe,/CDe
but
was
not
the
that
such
They
the
whets
cDe.
our
tions.
were
lacked
with
in
both
or
awaiting
with
concluded
of vchich
complex.
recognized
chromosomes
associated
authors
inheritance
Rh
F antigen
It w-ill be recalled
et al.
the
in the
They
detected
one
these
antigen,
genes
of the
f was
antigen
f antigen.
Hence,
the presence
of f in blood
a cc chromosome
cannot
be said invariably
to obtain.
our series,
f was not. found
in association
with chromosomes
therefore
cde
on
CDe,/cde
of type
an
antibody.
of
new
possibilities
of allelic
existence
combination
the
detected
pair
identification
the
requires
that
various
anti-f
with
containing
In
show-ed
a fourth
Ff
locus
al.
examining
one
to iisteract
of
c and
cells.
e are
e are
w-hich
to produce
together
the
When
CDe/cDE)
on the
would
the antigen
in drosophila.
t.he
on the
genes
c and
f antigen
is
to
same
e are
absent.
he the result
This hypothchromosome
on
opposite
The
occa-
same
chromosome
admits
of several
postulate
the existence
of alleles
of
f. There
is
evidence
to
indicate
that
alleles
exist.5
those
w-ho
favor
the
multiple
allele
theory
of
the
inheritance
of the
Rh
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
JONES,
STEINBERG,
2
I
Frequency
FIG. 2.-Frequency
frequency
with
the
antigen
by
the
the
simplest
r and
The
allele
of r.
If anti-f
mosomes
3
assumption
does
describe
appears
a new-
be doubled
to
5
6766
with
COs
be
that
the
as
number
system
the
of genotypes
array
simultaneous
presence
of f on
effect
cDe(f-).
equal
The
to
types
(n
Would
the
of certain
Rh
system
number
+
be
of
+
2)(n
increased
to
for
the
presence
of c and
cells)
contain
suggest
alsti-f.
is not
result
of
of
36
to
e (especially
never
“position
e on
chroamount
of chromosomes.
of
the
three
genotypes
the
loci
would
due
effect”
same
would
be
8 the
multiplied
possible
to the
the
chromosome,
t.w-o new’ chromosomes
1). If n equals
an
recognized.
a
c and
genotypes
that
1ff
locus
be to add
+
from
evidence
cde/cde
would
possible
is
Ff
the
alleles
3),/(n)(n
There
test
the
be
of
genes
proof a new
by
to
136, compared
with 36 s’hen
If the new antigen
proves
to
function
of possible
multiplied
Thus
be
a
f is determined
antigen
(4n + 2)/(n
+ 1) w-here
ts equals
the original
number
if we consider
only
the
common
pairs
of alleles
at. each
(Cc, Dd, Ee), n equals
8 and the actual
number
of possible
new-
equal
121
be typed
as CDe/cde
CDe chromosome.
Rh
in the
the
KRIETE
usual
antigen
mosaic
w’hich these
us w-ould
require
the postulation
locus
and
AND
4
S with which f Is associated
R#{176}
as part of the
exceptions
described
by
would
DIAMOND,
with which
CDe/CDe
would
which
f is assoeiated
with the
genes
duce.
ALLEN,
cde(f-)
by
an
number
and
amount
of geno-
55.
if not
many
those
occurs
all
antisera
produced
with
C or E,
commonly
used
by immttnization
the
presence
to
w-ith
of
anti-f
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
122
NEW
in
the
with
sera
used
to
C and
E,
errors
test
2 illustrates
figure
classified
tion
as
to the
the
(because
of f in
based
associated
in the
is difficult
and
potent
primary
will
use
appreciate
the
antigen
in fact
represent
are
studies
probable
the
most
cDE/Cde,
but
if it is f positive
sary
to
the
possible
the
depend
upon
presence
the
the
use
For
are
c, e. If
chances
two
types
of this
probably
be
it now
of
w-hich
of
in immuno-
CDe/cDE,
presence
sera
of finding
significance
engaged
testing
its
Geneticists
The
blood
ss-ould
the
of
the
a pure
future,
problems.
obviously
or anti-e
for
immediate
locus
of paternity
effect
the
laboratory
genotypes
of anti-c
is correct.
in differentiating
E,
this,
be misin rela-
that
f is
that
anti-f
a place
increased.
The
D,
field
typings
knowledge,
a fourth
useful
C,
In the
these
somewhat
genotypes
C1DE/cDe.
consider
which
serum
antigens
of
Sanger6
indicate
the assumption
of theoretic
is obvious.
anti-f
the
for
of our
analysis
complex
Rh
contaits
commonly,
the
occur
example
CDe.*
atsd
that
laboratory.
the
f negative
less
in
an
of CDe,.CDe
would
of anti-f
in the anti-c
sera)
used
stage
if f does
will find
W’ork
of which
sera
clinical
aid
in population
hematologic
both
an
As
containing
this
if f does
HOW-ever,
bloods
presence
anti-c
at
be
as
which
quoted
by Race
C or E, provided
and
general
that
consequence.
be introduced.
well
of the
in the
within
e is of no
with
data
w-it.h
anti-c
Will
a cross-over
on
ANTI-F
may
chromosomes
to envisage,
anti-f
AGGLUTININ
frequency
CDe/cde
present
It
c or
in typing
frequency
Calculations
rarely
if ever
was
for
RH
of blood
phenotype
is
CDe/cdE
or
CDE/cde,
or
becomes
the
antigen
have
tiot
neces-
f in
beets
results
tested
for
of anti-f.
SUMMARY
1.
An
example
2.
It
is show-n
of the
3.
The
that
significance
practical
new
anti-c
anti-Rh
and
of
the
serum,
anti-c
anti-f,
sera
may
is described.
contain
f is discussed
antigen
anti-f.
in
terms
of
its
genetics
and
importance.
IN
SULtARIo
1.
Es
describite
2.
Es
demonstrate
que
anti-c
3.
Le
significat.iois
del
atst.igeno
importantia
uii
exemplo
del
IXTERLINGUA
nove
factor
anti-f
pote
continer
e anti-c
f es discutite
its le systema
Rh.
anti-f.
in
relation
ANI)
RACE,
over
at
a
su
genetica
e
su
practic.
REFERENCES
1
body.
2
R.,
ROSENFIELD,
RACE,
anti-f.
R. R.
Brit..
A.
Genetics
RACE,
316,
AND
6 -
*
10:
E.
R.
J.
H.:
The
N.,
GIBBEL,
of
unequal
phenomenon
of
position
R.,
LAWLER,
1925.
The
SANGER,
R.,
SANGER,
R. R.:
A “new”
Rh
anti-
1: 975,
1953.
R.: Personal
communication.
effects
AND
crossing
effect.
S. D.:
Rh
the
Advances
genes
in
bar
locus
Genetics
allelonsorphic
in drosophila.
1950.
Nature,
3: 73,
to
C.
161:
1948.
-:
Blood
Appendices
derivation
space.
M.
117,
B.:
R.,
P.,
SANGER,
AND
STURTEVANT,
LEwIs,
VouEI,
to
of
Copies
Groups
the
t.his
equation
of tlsese
in Man,
paper,
Oxford,
Blackwell
containing
for
appendices
the
the
curve
may
of
be
Scientific
calculations
figure
obtained
2,
by
of
have
writing
1950,
Publications,
gene
been
frequencies,
omitted
to
the
for
authors.
p. 87.
and
economy
the
of
From www.bloodjournal.org by guest on August 3, 2017. For personal use only.
1954 9: 117-122
Observations on the New Rh Agglutinin Anti-f
ALAN RICHARDSON JONES, ARTHUR G. STEINBERG, FRED H. ALLEN, JR., LOUIS K. DIAMOND
and BERTRAND KRIETE
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