alae
srcit 25, 1961
LAXg
—
—_—
*
.
a
{1k--OBSERVED AND EXPECTED NUMBERS OF Ag(a—) CHILDREN
FROM VARIOUS MATINGS
or,
tied
No. Posits,
Mating
x)
Ag(at+)* Ag(a—)
0-99
of observed and expected
Cenrperi
of Ag(a--) children in families
sanoore
is at least one Ag(a —) chiid
wiert
Ag(a-+) x Ag(at+)
1-37
Ag(a+) x Agta)
0-49
2s (25 white, :
Cunperi
of observed and expected
Seof families with at least one
agi~) child, assuming an Ag-gene
10wnh in table nN
a
16
32 spe
at
50 (seu!
21
Test
Crexperise
10 (gge"
en aa
‘eloped.
,
pequency of 0-66
Canparison ef observed and expected.|
ner
of families with at least one
again) child, assuming an Ag-gene
in
ties Wer
eactors was hic
at) x Ag‘a_
———
Ag(a+). The.
Qeupmrison of observed and expected
seoraatsec of : recessives in Agfla—)x
~ Ag(2 —) matings
included in the
‘CISIVE in testing
Ag(a~) x Agl@a—)
“The results of these computations are summarised in
gable uit, which includes also the results of Ag(a—) x
Agia) matings. Although the numbers are small, this
peeliminary family analysis is consistent with’ the genetic
ative offspring
is
léritance of the
negative
0-03
rai membersof thie families (table ). Of 56 parents,
57%, were found to be Ag(a+).
positive and
id negative og.
© Offspring of
with
Ag(a+) x Ag(a-+)
Iyx*=2-88 with 5 degrees of freedom; 0-8>Pr>0-7,
rom the Unite:
X
of observed and expected
i, Ag(a—) children in families
phere there is at least one Ag(a —) child
“xtensive studi.
typothesis. On the basis of segregation in this group of
tmmnilies, no evidence of close linkage was found with the
ig, and positive
the allelic £ene
following blood-group systems and haptoglobins types:
ABO, Rh, MN, Duffy, Kidd, and P. Analyses of 30 twin
pairs to be reported elsewhere were also consistent with
€ controls the
‘EN
whe genetic hypothesis.
a—)
Totat
-
|
3
|
‘Qo
|
a
1
|
223
3
38
-~
Jasiedendence of the Ag and Other Known Inherited Systems of
Senwn-proteins
,
_
.The reactions in the panel sera showed that the Ag
reacoons were independent of rheumatoid factor and of
haptoglobin, transferrin, and y-globulin types.
The
vegregation of the Ag“ and Ag genes in families was also
mdependent of these systems. Since the Ag(a +) factor
San «-globulin it is also independent of another recently
te
“oduct of the
described inherited y-globulin system designated In, by
Ropartz (1960). In collaboration with Dr. J. Hirschfeld,
ow Stockholm, Ag tests were carried out on 113 sera of
koown Gc types, which are distinguishable by immuno_ sectrophoresis (Hirschfeld and Beckman 1960). Positive
and negative Ag reactions were found in subjects of Gc
ned Ag® and
‘esulting from
f families in
—)> Ag(a _
‘spring, given
ive offspring
‘er of families
en.
sethods sum3 Of compariincluded fur
and expected
types 1-1, 2~1, and 2-2, the percentage of reaction being
a the same order in all these groups. Hence the Ag
system is independent of all other known inherited
'tum-protein differences. The Ag(a+) antibody is also
éstinct from the factor in normal human serum giving a
Fetcipitate in agar with red-cell hamolysates (Peetom et
al, 1960); the antigen in the latter case is not present
® serum and does not react as an a-macroglobulin. The
3] number of
facies in the
y=frequency
number ov!
‘en the tors:
factor is present in too many normal sera to be
ictive protein; which in any case migrates in the
“gion in immunoelectrophoresis (Zach and Zimmer’ Mann 1959),
ent of the
Discussion
The Precipitin in the patient’s serum defines the
"Presence of a factor in some sera from all human popula-
>is needed
which the
“gen appearsto be genetically determined, so that a new
2 frequency.
r the third
qin 2 larye
which the
.ency
oe
bens so far tested. The antigen is an «,-macroglobulin
| the precipitin a 7S-y-globulin. ‘The presence of the
Polymorphic system in human serum-proteins has been
: ftvealed,
Besides being of genetical and anthropological interest,
was
ses in the
Saran)
THE LANCET
ORIGINAL ARTICLES
the finding of a specific precipitin in the patient’s serum
SUZ&oei2
637
suggests that isoimmunisation by human serum-proteins
may occur. Though there is no direct evidence that the
precipitin was induced by the many transfusions which
the patient received, this would seem to be the most
probable explanation of the findings. In all, 61 sera of
subjects who had received multiple transfusions have been
tested, and 3 of these have given definite precipitation
lines with some of the panel sera. The reaction whichis
the subject of this paper was the strongest, and the
specificity of the others, which are different from the Ag
system, will be reported later. Sera of forty persons who
had not received transfusions failed to give precipitation
lines with the panel sera.
Though ourpatientinitially tolerated transfusions well,
during the past 2 years he has had pyrexical reactions after
most, but not all, transfusions. Whether these reactions
take place only when donor serum is Ag(a+-), and represent
an antigen/antibody reaction, is now being investigated.
Other properties of the precipitin will be described
elsewhere. The unusual history of this case may be
irrelevant, since the other subjects showing precipitins had
typical thalassemia.
Summary
A serum from an anzmic patient who had received
approximately 50 transfusions was found to give strong
precipitation with sera of some, but not all, normal
subjects.
It appears that an antigen/antibody reaction is involved.
The antigen in some normal subjects is an a,-globulin,
and the antibody in the patient is a 75-y-globulin. The
antigen appears to be inherited according to simple
mendelian rules and its frequency varies in different racial
‘groups.
It is possible, though not proven, that antigen/antibody
reactions were responsible for severe post-transfusion
reactions in the patient, and similar processes may be
involved in other unexplained post-transfusion reactions.
We are indebted to Dr, Fred Stohimnan and Dr. Archie McKinney
for supplying the serum from the patient; to Dr. Sheldon Dray and
Dr. Kurt J. Bloch for valuable help and advice; to Dr. J. Hirschfeld,
Stockholm, for collaboration with the Gc tests; to Dr. George A.
Silver, Montefiore Hospital, New York, for allowing access to
families under his care; to Dr. Arthur G. Steinberg for supplying
blood from American Negro families and carrying out the y-globulin
typing; and to Dr. Lyman Crittenden for assistance with the linkage
studies. Most of this investigation was undertaken while one of us
(A.C.A.) was a visiting scientist at the National Institute of Arthritis
and Metabolic Diseases.
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