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Naturally
Occurring
Human
Antibodies
to Pepsin-digested
By
Human
I. D.
serum
antibodies
with
antigenic
vealed
were
by
found
digestion
in 29.2
from
369
hospitalized
only
These
antibodies
cific
for
IgA
and
N
for
variability
ATURALLY
abundantly
with
in
human
incomplete
to
specificity
for
of
antigens
anti-
to
be
re-
or
to
immunoglobulin
globulin
and
of
by
rabbit
by
During
normal
human
human
sera
enzymatic
now
antibodies
course
IgA
with
digestion
of
studies
re-
of
myeloma
contain
proteins,19
antibodies
digestion
been
informa-
enzymatic
the
various
showing
have
Considerable
human
uncovered
uncovered
reor
was
processes
serum
reports.12
both
digestion
some
no
these
found
ANTIBODIES
IgG
antibodies.1318
that
of
not
disease
SERUM
published
regarding
rates
apparent
presence
specific
proteins
but
IgA
subgroups
IgA antigens
was
in
human
determinants
anti-Rh
relative
became
The
antibodies
to
IgA
sera
concentrations.
on
many
accumulated
IgG
discerned.
HUMAN
sites
JR.
individual
to either
determined
alterations
Con-
reactivity
in
lationship
genetically
lated
intact
antigenicity.
various
against
lating
upon
WILLIAMS,
pepsin-digested
found
IgA
of
in
for
also
reactivity
spe-
fragment
documented
has
tion
was
studied.
OCCURRING
specificity
it
F(ab’)9a
C.
different
re-
to be
R.
AND
react
patients
shown
dependent
bonds
siderable
which
SOLTIS
of IgA with
pepsin
per cent
of the sera
on the
were
D.
determinants
were
sites
disulfide
R.
WILSON,
IgA
of
showing
IgA.
This
report
describes
immunochemical
and
serologic
characterization
of naturally
occurring
human
antibodies
for pepsin-digested
IgA. Although
the immunologic
specificities
of these
anti-IgA
globulins
vary,
no distinct
anti-Gm
or anti-IgA
allotypic
ship
specificity
may
have
has
to
yet
await
become
further
apparent.
definition
Elucidation
of
of such
genetic
markers
on
a relationhuman
IgA
molecules.2#{176}’21
VIATEmALS
Clinical
From
the
Minn.
N.
chemistry
and
Departments
the
from
of
patients
Medicine,
County
Bernalillo
METHODS
of
a large
University
Medical
general
of
Center,
( Bernalillo
hospital
Minnesota
Hospitals,
Univer#{241}ty of
New
County
Misineapolis,
Mexico,
Albuquerque,
Mex.
Submitted
February
Supported
in
the
USPHS
I.
DODD
sofa
WILSON,
9,
Medical
S0LTIs,
School,
Department
N.
1970;
by
aCcepte(l
Grants
part
by
M.D.
AM
grants’
:
March
13690-01,
from
Assistant
School,
Philosophical
D.
Chairman,
qUeT(jUe,
in
Medical
American
RONALD
part
and
Minnesota
390
sI)ecimens
AND
the
Society
M.D.,
Minneapolis,
of
Minn.
during
Medical
Medicine,
the
Fellow,
Minn.
1970.
11803-02
Minnesota
Professor,
Minneapolis,
20,
AM
when
of
C.
of
of
a
this
Medicine,
from
University
Daland
study
Fellow
was
Mexico
M.D.
Medical
of
of
the
performed.
University
Ju.,
\VILLIAMS,
New
13824-01
Medicine,
was
part
Depart1nent
University
of
Wilson
AMAI
Foundation.
Department
Dr.
period
RALPH
and
Arthritis
of
: Professor
School,
Minneand
Albu-
Mex.
BwoD,
\OL.
.36,
No.
3 (SEPTEMBER),
1970
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
HUMAN
ANTIBODIES
Table
TO
1.-Reactions
Tanned
Reciprocal
391
IA
of Sera from
Cells
Coated
of
369 Patients
Tested
with
Pepsin-digested
for
Titer
Agglutination
IgA
No.
Positive
0
2
4
8
16
32
265#{176}
51#{176}
29
11
6
2
64
71.8
per
#{176}
cent
Center
human
andria,
)
Va.
All
sera
to
remove
A
.
were
panel
of
heated
to
50
or
of
background
of
human
described
were
from
In
sera
presence
30
with
and
antibodies
positive.
agglutinating
antibodies
( Cooke
system
patients
minutes
were
of
microtiter
from
isolated
by
were
freed
then
arthritis
absorbed
before
to
Engineering
rheumatoid
were
sheep
with
pepsin-
Co.,
Alex-
also
red
tested.
blood
cells
use.
electrophoresis
as
DEAE-cellulose
many
instances,
of
most
sera.
of
In
was
Tomasi
et
this
) as
as
judged
by
estimated
by
IgA
degrees
Oudin
preparations
were
of
8.2
with
against
specific
still
contained
quantitation.25
from
free
IgC
pH
of purification
proteins
tube
The
from
diffusion
myeloma
isolated
block.24
background
ranging
immune
IgA
starch
admixed
buffers
in high
isolated
or
from
phosphate
secretory
These
Pevikon23
possible
resulted
IgC,
by
al.26
as
instances,
provided
on
much
using
the
other
( 2-5%
IgC
IgA
by
the
29.2percent
isolated
IgA myeloma
proteins
was used to prepare
individual
samples
IgA used to coat sheep
red blood
cells by the tanned
cell technique.22
anti-IgA
source
while
drop
heterophile
M.
traces
two
56#{176}Cfor
elimination
anti-IgC
for
a
peaks
Nt to 0.15
tests
screened
using
elution
subsequent
as
negative
agglutinating
stepwise
0.01
2
were
electrophoresis
by
1
256
IgA
A panel
of 10
of pepsin-digested
Mycloma
proteins
zone
2
128
showed
)
Medical
digested
of
pooled
IgC
Another
human
as
colostrum
judged
by
immune
or
a 1:100
diffusion.
Pepsin
digestion
2: 100
of
ratio
Specificity
of
pepsin
digestion
IgA mveloma
pepsin-digested
on
of
separations
IgC,
and
digestion
cm.
at
reacting
inhibition
human
IgA
of
Sephadex
accomplished
37#{176}C for
at
periods
pH
of
4.1
18
using
hours
either
a
the
of
were
and
anti-globulins
C-200
gel
whole
aimed
colostral
IgA,
separated
by
in
inhibition
studies.
characterizing
pepsin-digested
10-40
per
flow
proteins.
in
molecular
cent
by
IgG,
myeloma
upward
their
overnight
lgA
uncovered
isolated
undigested
IgA
also
at
or
on human
a panel
of
pepsin-digested
used
filtration
sites
using
115
individual
IgA
columns11
with
studies
Sephadex
class
sucrose
were
density
runs.
Antisera
to
100
was
digestion
hours.19
whole
peptic
x
2.5
using
gradient
10
colostral
Physical
done
for
materials
and
human
anti-globulins
was
monitored
by
proteins,
products
C-200
IgA
ratio,
enzyme/protein
The
isolated
enzyme/protein
against
l)iWeekly
volume
the
1 ml.
of
complete
IgA
proteins
and
site
revealed
by
F( ab’
injections
Freund’s
IgA-deficient
peptic
)2
portion
of
of
0.2-1.0
mg/mI.
adjuvant.
sera
in
human
These
an
attempt
IgA
were
solutions
antisera
to
prepared
in
antigen
mixed
of
were
render
then
them
rabbits
absorbed
specific
by
with
giving
an
with
for
the
equal
whole
antigenic
digestion.
RESULTS
In
were
coated
the
369
positive
with
consecutive
sera
for anti-y-globulins
pepsin-digested
IgA.
tested
from
capable
Ten
of 50
hospitalized
of agglutinating
sera
from
patients
sheep
patients
with
29.2 per cent
erythrocytes
rheumatoid
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
392
WILSON,
Table
2.-Specificity
of a Human
Erythrocytes
Inhibitors
Anti-y-globulin
Showing
IgA
Coated
with Pepsin-digested
as Measured
by Inhibition
Tested
Lowest
SOLTIS
Concentration
Inhibiting
IgA
myeloma
Iv
> 1.0
mg/cc.
IgA
myeloma
Ra
>
1.0
mg/cc.
Whole
IgA
myeloma
Fr
>
1.0
mg/cc.
Whole
colostral
>
1.0
mg/cc.
Whole
IgC
IgA
Pepsin-digested
colostral
IgA
myeloma
Iv
0.125
Pepsin-digested
IgA
myeloma
Ra
0.06
Pepsin-digested
IgA
myeloma
Fr
Pepsin-digested
IgG
also
relatively
was
IgA
myelomas
seen
tination
or
In
that
This
recorded
some
did
furnished
Further
0.01
Nil
data)
from
The
typing
of
IgA
from
a Sephadex
peptic
digestion
11.05
digestion
other
IgA
results
of
revealed
Fab’
Patterns
did
of
not
reactivity
pepsin-digested
parallel
in
findings
by
The
are
inhibit
but
others
IgA
subclass27’30
antisera
products
of whole
digested
re-
was
as
kindly
resulting
from
Figure
colostral
both
with
IgA
and
the strong
of IgG (Wilson,
I ) is comparable
1 com-
and the
without
resemblance
unpublished
to that
obtained
studied.
using
shown
pepsin
results
agglu-
apparent
did not.
was
determinants.
demonstrated
and Fab’
of
digestion
using
which
G-200
column
colostral
IgA
studies
Ho
the
myelomas,
uncovered
undigested
inhibition
pepsin
to
( fraction
of agglutina-
of three
anti-y-globulins
inhibited
polymers
inhibition
protein
by
the
human
A repre-
myelomas.
Many
similar
data
and distinct
specificity
these
IgA
product
myeloma
F( ab’)2a.
in
These
of
showed
reactions.
inhibition
any
myelomas
the
agglutinating
pepsin-digested
distinct
to determine
contained
sera
with
cell
relationship
isolated
H. G. Kunkel.
were
performed
of
determinants
IgG,
the
these
sera
IgA,
molecules
of
IgA
mg/cc.
IgA
extend
apparent
mg/cc.
1.0
2. No
colostral
heterogeneity
by
myeloma
while
IgA
1.0
>
with
However,
cysteine.
Other
studies
have
of the protein
peaks
to F( ab’)2
two
tion
to
on
any
The
.
done
bear
of
of two
were
>
tanned
Table
in
115
exposed
mg/cc.
mg/cc.
instances
pepsin-digested
pepsin-digested
eluants
products
shown
whole
with
not
digestion
pares
of the
IgG.
instances,
by Dr.
studies
peptic
inhibition
is
mg/cc.
1).
reactions
IgG,
0.03
seven
showing
pepsin-digested
many
measured
in
result
apparently
corded.
and
by
most
However,
.
( Table
found
were
whole
In
)
1 : 16
antibodies
experiments
sites
to
primarily
with
was
inhibition
in
of
experimental
tion
reactions.
( 1 :2
1 :256
tested
sentative
for
to
<
positive
titers
specificity
was
IgA
gave
low
of 1 :32
IgA
Agglutinations
> 1.0 mg/cc.
Pepsin-digested
The
of Tanned
Reactions
Protein
Whole
titers
WILLIAMS
Agglutination
Myeloma
Ra
Whole
arthritis
AND
these
in
Table
digestion
obtained
were
with
products
from
colostral
IgA
3.
data
indicate
that
These
present
in greatest
fraction
I were
concentra-
also
inhibitory
agglutination.
of human
IgG
and
further
attempts
are
summarized
anti-y-globulins
for
pepsin-digested
to
IgA
elucidate
in
Table
the
4.
cells
coated
specificity
Some
with
preparations
variability
of
various
were
these
was
tested
reactions.
found
in
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HUMAN
ANTODIES
393
IA
TO
Optical
Density
(280
mp)
200
Elution
Fig.
1.-Elution
whole
patterns
colostral
measured
IgA
by
teins
used
similar
to
slightly
optical
inhibition
F(ab’)2
and
when
Table
density
for
smaller
ments
from
whole
in parallel
3.-Specificity
digested
at
of
IgA
Whole
colostral
IgA
F(ab’
F(ab’)9a,
Fab’,
IgA
colostral
I,
)2a,
IgG
are
with
showed
whole
the Human
for Various
by
IgA
IgA
Ho
colostral
IgA
colostral
Ho
Ho
IgA
>
>
Peptic
and
the
was
four
peaks
pro-
that
I, although
Ouchterlony
are
only
experi-
IgA.
Directed
Digestion
against
as
Pepsin-
Reactions
Lowest
Protein
Concentration
Inhibiting
Agglutination
1
Agglutinator
2
1 mg/cc.
1 mg/cc.
0.24
0.031
IgA
in
colostral
Anti-y-globulins
Products
of
The
Fraction
deficiency
undigested
Inhibition
of
comparison.
designated.
IgA
concentration
coefficients
for
also
of colostral
Protein
Sedimentation
shown
colostrum,
digestion
column.
Agglutinator
myeloma
I,
Fraction
mit.
are
(ml)
of peptic
G-200
Tested
Whole
Fraction
280
from
Measured
Inhibitors
products
studies
Fab’
than
tested
of the
a Sephadex
Volume
>
1 mg/cc.
<
0.004
mg./cc.
<
0.004
mg/cc.
mg/cc.
mg/cc.
0.0005
mg/cc.
< 0.004 mg./cc.
0.5 mg/cc.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
394
SOLTIS
WILSON,
Table
4.-Variability
in
Patterns
of
Anti-y-globulins
Reactivity
Cells
Whole
IgG
Ripley
Agglutinator
GB.
512
Sera
WILLIAMS
Containing
with:
Pep.f
IgA
Ra.
Pepj
IgA
Iv.
Pepj
IgA
Fr.
Pep.f
IgA
Ru.
Pep.f
IgA
1g.
2
2
2
4
0
2
16
2
2
256
2
8
4
4
4
L.K.
J.P.
32
0
8
0
8
0
256
16
0
8
4
8
4
2
2
2
0
S.V.
32
2
16
2
4
2
16
8
J.M.
32
2
0
16
16
J.C.
0
0
0
0
4
0
0
8
32
2
0
2
4
J.C.
0
0
0
2
0
0
0
16
0
0
0
4
2
2
2
Waller,
Rich-
128
Anti
*
mond,
CD
Ripley
incomplete
4
Pep.l
IgA
Er.
D.P.
M.M.
8
64
anti-Rh
antibody
obtained
from
2
0
Dr.
Marion
2
Va.
I
Results
were
expressed
used
as
or within
the
one
here
strength
and
The
well
addition
IgA.
as
The
digested
preparations
antiserum
75
specificities
the
were
several
equal
coats
discernible
for
in
fractions
IgG,
of
between
pepsin-digested
Fig.
2.
in
It
fractions,
be
anti-CD
showed
that
( IgG )
with
pepsin-digested
agglutinating
coated
instance,
of
different
a siwile
195
anti-y-
were
present
anti-CD
activity
present
one
within
cells
for
within
or
pepsin-
conventional
Ripley
anti-y-globulins
in
heterogeneity
present
seen
with
filtration
instances
whereas,
The
reacting
gel
seven
immunoglobulins
can
of
by
In
195
reacting
fractions
of
capable
separated
demonstrated.
to various
whole
types
antibodies
in
only
anti-y-globulins
two
was
with
clearly
with
195
for
relationship
ultracentrifugation.
of antibodies
reacting
In
pepsin
anti-y-A
agglutinators
agglutinating
detected
was
is illustrated
as
no
studied
gradient
were
types
globulins
of
was
density
agglutinator
serum
yA
rabbit
IgA.
class
antibodies
specific
various
with
of the
Moreover,
of antibodies
IgA
sucrose
75
with
titers
reaction
used.
or titers
molecular
after
tanned
Coombs
pepsin-digested
pepsin-digested
IgA
of
IgA
presence
IgG
cells
when
dilution.
relative
the
using
equivalent
pepsin-digested
a
Coated
Pepj
Col.
#{176} IgA
Pepsin
IgG
Ripley
#{176}
of
AND
Ripley.
pepsin-digested
195
fractions
in
this
could
readily
be differentiated
on the basis
of inhibition
reactions.
The
19S agglutinator
for whole
Ripley
coated
cells
was
inhibited
by IgG
isolated
by DEAE
chromatography,
as well
as by aggregates
of IgG at conserum
centrations
IgA.
of
195
showed
digests
IgG
Attempts
were
well
as
anti-globulins.
as
quantitative
not
antibodies
made
differences
whole
IgA
specificity
normal
human
presence
of
IgA,
possible
These
IgG
and
clinical
findings
within
1gM
by
pepsin-digested
pepsin-digested
measured
of
85
pepsin
not by
IgG.
pepsin
by
IgA
Oudin
agglutinators
tube
similarities
among
the patients
shown
in Table
5 indicated
no
a group
IgA
IgA
or by several
of 0.01 mg/cc.
but
relate
the
nor
for
of isolated
to
of
to
by
with
pepsin
digests
of colostral
proteins
at concentrations
aggregates
concentrations
serum
tion,
nor
but
mg./cc.,
inhibition
by
of IgA myeloma
whole
these
0.01-0.005
agglutinating
consecutive
patients
to
quantitashowing
significant
between
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
HUMAN
ANTIBODIES
TO
395
IA
s.V.
4096
0. D.
TITER
Fig.
2.-Separation
patient
S.V.
digested
by
represents
in Sephadex
occurring
striking
example
5.-Mean
Subjects
Sera with IgA
(n = 15)
of
multiple
anti-globulins
(n
the
15
site
patients
whose
Rabbits
IgA
were
absorbed,
first
from
found
between
when
tested
This
F( ab’)2a
these
Groups
IgG
with
which
by
and
with
pepsin
#{176}
of
agglutination
findings
anti-pepsin
In
1gM
mg%
1336 ± 261
146 ± 97
1349
155
site
addition,
among
but
( ab’ )
These
± 338
IgA
111
±
agglutinators
no constellation
patients
whose
sera
and
of clinical
contained
that
this
other
antisera
to
obtained
produce
in
IgA
was
antisera
and
either
whole
IgA
or F
in agar
gel. However,
one of these
( ab’ )
pepsin-digested
was
IgG
antiserum
the
this
antisera
were
either
than
attempt
IgA,
then
followed
by
derived.
No precipitation
agglutinating
by
an
whole
reaction
in
was
reaction
not
in
way
sera
deficient
the F ( ab’ ) a
capable
the F( ab’ )2a molecule
inhibited
agglutination.
F
site.
these
absorbed
immunodiffusion
Fab’
mg%
of
agglutinators.
IgA
proved
1 : 1000.
contained
agglutinators.
was discernable
immunized
the
for
antisera
in Two
Agglutinators
with
agglutinators
serum
the same
or diagnoses
site
protein
a patient
276 ± 146
deviation.
anti-pepsin
specific
from
anti-pepsin-
agglutinators
pepsin
standard
without
syndromes
fractions
(IgG),
in
mg%
266 ± 103
IgA
70
from
site
70)
=
0
serum
occurring
Serum
Immunoglobulin
Concentrations
with or without
Anti-pepsin
Site IgA
pepsin
without
of
Ripley
pneumonia.
Kiebsiella
IgA
Sera
G-200
anti-whole
and
a
necrotizing
filtration
naturally
anti-pepsin
digested
IgA antibodies.
To the left, the higher
materials
(19S) were eluted
first. Protein
concentration,
shown
by
was determined
by optical
density
at 280 mjz. The vertical
bars
location
and titer of antibody
activity
on the gradient.
This serum
Ripley
molecular
weight
the dashed
line,
indicate
the tube
Table
gel
containing
inhibited
by
IgA
whole
or pepsin-digested
was
pepsin-site
reacting
since
the
at
IgA,
IgG.
with
whole
three
a titer
of
fraction
I,
It is apparent
some
IgA
portion
and
of
Fab’
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
396
WILSON,
F
SOLTIS
AND
WILLIAMS
(ab’)2,,
L
Fig.
3.-Schematic
antigen
by
respectively.
stops.
The
The
peptic
while
line
portion
those
a
of
Area
revealed
by
IgAl
and
shows
the
H
the
IgA
point
the
at
which
remains
chains
enclosed
the
identify
molecule
heavy
“b”,
peptic
demonstrating
L
of the
parts
polypeptides.
antigen
of
digestion.
dashed
F(ab’)oa
digestion,
to small
the
diagram
revealed
to
by
proposed
light
peptic
right
of
of
heavy
of
intact
line
after
“a”
the
rectangle,
is the
that
many
sera
a
uncovered
the
chains,
digestion
relatively
the
site
and
are
IgA
peptic
degraded
proposed
site
of
digestion.
DISCUSSION
The
findings
occurring
presented
antibodies
human
peptic
digestion.
can be inhibited
Reduction
presence
This
suggests
antigenicity
fragment
the
are
similar
to
in a greater
intact
was
the finding
than
75 in size
data
against
is specific
but not by
antigenic
3 demonstrates
These
)
that
of the
interesting
was
greater
Figure
F( ab’
resulted
indicate
directed
This
reaction
by F( ab’ )2a
of the
of cysteine
capacity.
the
here
Fab’a
by
than 100-fold
disulfide
site
those
on
are
of the
for
necessary
pepsin
to
site
by
that
it
IgG.
maintain
on
IgA.
product
of IgA
dimers
in this agglutinating
this
previously
IgA
in
peptic
digestion
in the
diminution
in inhibitory
bonds
determinants
proposed
naturally
for pepsin-digested
IgA
whole
IgG or pepsin-digested
that
a digestion
produced
inhibition
to
site
contain
antigen
on the
recorded
in
the
IgA
IgG
Also
which
system.
molecule.
pepsin
site
agglutinator
system
in that
this
latter
reaction,
like
IgA,
is specific
for
determinants
on IgG
uncovered
by peptic
digestion
and
is also dependent
upon
the integrity
of disulfide
bonds
for its reactivity.13’14
The
IgG
pepsin
site apparently
resides
on the Fd portion
of the F(ab’)2
molecule.14
The failure
of
pepsin-digested
that
the
contains
found
ferent.
75I3.14
in
to
portion
of
the
IgA
pepsin-site
between
Inhibitory
Moreover,
195
IgG
Fd
most
the
inhibit
the
F( ab’)20,
IgA
rather
antigen.
However,
IgG and IgA pepsin
reactions
are specific
anti-IgA
size
whereas
Finally,
no
most
correlation
pepsin
site
anti-IgG
has
pepsin
than
site
partially
in
reaction
spite
site antigens,
they
to the immunoglobulin
agglutinating
pepsin
been
also
digested
of
are
antibodies
site agglutinating
apparent
in studies
suggests
light
the
chains,
similarities
distinctly
difclass involved.
appear
to
be
antibodies
are
between
the
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
HUMAN
ANTIBODIES
presence
in
or
titer
individual
Previous
Gm
of
Recent
can
ble
IgA.
found
agglutinating
has
set
antibodies
a precedent
et al.
for
have
to
or
genetic
normal
to
described
serum
in
serum
that
in
IgA
a relationship
anti-IgA
persons
when
similar
to
antibodies
deficient
in
exposed
to incompati-
of
produce
IgA
antibodies
reactions.
specific
found
markers
concentrations
are
been
IgA.20’21
occurring
that
against
IgA.34
These
and urticarial
transfusion
subgroups
pepsin-digested
suggest
on
antibodies
agglutinating
chain
has
of
appeared
naturally
demonstrated
anti-IgA
with
a variety
subgroups283#{176}
been
site
to heavy
variability
for
has
recently
class-specific
pepsin
considerable
Vyas
antibodies
anti-IgG
sera
IgA
have
for
anti-
are
clinically
Recently,
we
secretory
( Wilson,
IgA
data).
significance
of
to
found
these
disease
in this
naturally
or
serum
Studies
by
Lawrence
in
product
sera in
study.
possibly
antigen,
a degradation
is present
Anti-IgG
pepsin-site
antibodies
observations
invite
formed
Whether
against
this or
the
for
and other
pathologic
that
a circulating
some
other
and
auto-
Williams
as
these
No
could
as
of
These
autoantibodies
true
immunoglobulins.
tentatively
demon-
been
awaits
a 3-55
the IgG
mg/cc.17
isospecificity.
are
the
that
contains
to 0.03
up
well
product
as has
to determine
of these
intriguing
unknown.
indicate
which
antibodies
system3#{176} is valid
necessary
if any,
is
concentrations
of IgG,
concentrations
degradation
explanation
such
isohemagglutinin
be
antibodies
immunoglobulin
have
speculation
data
will
implications,
occurring
entities
substance,
pepsin-site
strated
site
relationship
pattern
limited
specificity
in anaphylactoid
relationship
be
known
Individuals
unpublished
containing
obvious
which
produce
of
The
pepsin
a distinct
Although
serum.334
bodies
important
anti-IgA
agglutinating
no
the
work
in human
have
yet
system
IgA
sera
various
as
either
with
demonstrated
of
molecules,
to
and
markers.’4’15
affinity
the
anti-IgG
studies
have
genetic
the
of
397
IA
sera.
antibodies
and
TO
further
inquiry.
These
potential
physiologic
anti-y-globulins.
and
ACKNOWLEDGMENT
The
authors
appreciate
the
expert
assistance
of
Mrs.
Charlotte
A.
Raich
and
of
rheumatoid
Miss
Jean
Emmons.
REFERENCES
1.
Franklin,
E.
M#{252}ller-Eberhard,
An
unusual
C.,
H.
in
patients
with
rheumatoid
Med.
105:425,
1957.
Kunkel,
H.
M#{252}ller-Eberhard,
lation
and
toid
factor”.
3.
Specificity
the
the
fixation
high
certain
J.
E.
: Studies
of
Invest.
H.,
reaction
toid factors
and gamma
Med. 114:257, 1961.
4. Singer,
J. M., and
latex
of
Franklin,
J.
J. Clin.
of
serologic
Amer.
Exp.
5.
W.,
diagnosis
J. Med.
and
on
the
C.,
and
the
iso-
Jr.,
based
between
globulins.
1959.
H.
G.:
Med.
32:142,
6. Vaughan,
Exp.
Plotz,
C. M. : The
test. I. Application
to the
M. :
75
gamma
B.,
Miller,
Cryoglobulinemia
between
a gamma
mac-
globulin.
Amer.
1962.
J. H.,
H. : Quantitative
rheumatoid
factor.
Ellis,
P. J.,
considerations
J. Immunol.
and
Marof the
81:261,
1958.
rheuma-
J.
Dora’ard,
Ziff,
interaction
and
arthritis.
1956.
J.,
and
on
shall,
“rheuma-
38:424,
Kunkel,
J.
21:888,
LoSpalluto,
roglobulin
characterization
H.
of
serum
arthritis.
C.,
H.
Fudenberg,
H.
component
weight
R.,
G.:
H.
J., and Kunkel,
protein
molecular
2.
Holman,
7.
Harboe,
Properties
in
M.,
of
human
Rau,
various
J. Exp.
J. C., and
sera.
8.
Allen,
bodies
to
genetic
B.,
and
anti-y-globulin
types
Med.
of
K.:
factors
121:503,
Kunkel,
Aho,
H.
gamma
1965.
C. : Antiglobulin
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
398
SOLTIS
WILSON,
after
multiple
transfusions.
Science
139:418,
1969
1963.
Williams,
L-chain
R.
sites
acting
on
with
Nat.
niczko,
Sci.
C. :
J.,
A
I.
Wailer,
J.
: Immunochemical
enzymatically
globulins.
95:501,
and
H.
H.,
factor
in
and
Kunkel,
H.
human
C. :
Kunkel,
sera
revealed
anti-Rh
by
Vox
of
the
antigenic
site
15.
16.
Mandy,
normal
genic
yG
Scand.
J.
rabbits.
pepsin
J.
Lawrence,
J.
18.
and
human
Wilson,
I.
125:233,
Sang.
and
groups
20.
Vyas,
C.
( 1 ), the
Am
N.,
first
immunoglobulin
U.S.A.
gen.
Gamma
A.
Kunkel,
H.
globulins-detection
In:
Symposium
Globulins.
Symposium
1967.
C.,
H.
H.:
Acad.
C.,
and
Yount,
which
of
lacks
the
and
light
1968.
Prendergast,
R.
human
immunoglobulin
in
the
A
alpha
polypep-
153:647,
1966.
and Franklin,
proteins
Nature
E.
C.:
subclasses
differing
in
( London)
212:
1966.
human
to
due
to
2:312,
by
!nvest.
H.
feeding
48:
H.
Anaphylactoid
reEng.
A., and
transfu-
with
L.,
anti-IgA.
Perkins,
H. :
Serologic
and
its
34:573.
Springer,
group
and
1968.
Blood
35.
1969.
N., Perkins,
H. :
F.,
New
antibody.
Holmdahl,
anti-IgA
fusion.
H.
transfusion
associated
Fudenberg,
Wenner-Cren
Press,
C.
reactions
-,
Immuno-
Taswell,
anti-IgA
H.
Lancet
P.,
: Anaphylactic
J. Med. 280:188,
Fudenberg,
globulins.
1968.
A.
actions
Blood
Interna-
IgA
5:203,
J.
34.
Sci.
antibodies
Pergamon
A.,
128:1223,
myeloma
C.
of a genetic
antion Human
Anti-Human
Series,
to
Med.
subclass
heavy
Med.
Schmidt,
human
G. : Human
C.
C. : A
( yA2 )
chains.
to
32.
of human
Nat.
A
heavy
sion
marker
Proc.
J.
digestion.
Fudenberg,
Solo-
Exp.
distinguishable
33. Vyas,
1969.
64:1211,
21.
7A2
and
genetic
M.,
common
Abel,
H.
H.
Cleich,
immunoglobulin
A ( IgA ) revealed
by
peptic
Clin. Invest.
48:2409,
1969.
E.
J.
linking
Exp.
human
their
of
R.
Tan,
system
differences
chemistry
digested
Williams,
of
determi-
R. A. : Character-
M.,
antigenically
bodies
13:233,
diffusion
1963.
Jr.,
chains.
Science
Feinstein,
D.,
1496,
1967.
enzyme
gel
31. Fudenberg,
H. H., Cold,
E. R., Vyas,
G. N., and Mackenzie,
M. R. : Human
anti-
agglutinators
with
D.,
distinct
1967.
Williams,
anti-y-globulin
M. : Serum
Vox
of
or
pepsin-digested
Med.
H.
of
on
Two
anti-
papain
99:815,
Jr.,
with
antibodies.
Jr. : Two
for
by
1954.
secretions.
Kunkel,
tide
factor
Specificity
sensitized
anti-Rh
19.
of
Exp.
WaIler,
erythrocytes
serum
electrophoresis.
A. : Subgroups
of
yA
immune
globulins.
Proc. Soc. Exp. Biol. Med. 122:910, 1966.
29. Vaerman,
J. P., and Heremans,
J. F.:
30.
new
C.,
reacting
y-globulins.
A
12:33,
globulin
immune
bonds
J.
based
Path.
B.,
J., and Kunkel,
human
yA-globulins
Subclasses
anti-
pepsin-di-
Acta.
Immunol.
T.
R. C., Jr. : Studies
factors
of
uncovered
digestion.
17.
:
Invest.
1:141,
W.
1966.
III.
determinants
di-
1966.
globulin.
W.
sup-
electro-
1965.
28.
at
T.
Crey,
disulfide
8:133,
pepsin
by
66:369,
Lab.
gamma
external
27.
Lawrence,
45:714,
detected
human
Microbiol.
in
B. : Heterogeneity
factors
gested
factors
y-globulins
by
Invest.
J.
Natvig,
y-globulin
and
splitting
and
revealed
J. Clin.
gestion.
Jr.,
J. : A new
Prendergast,
an
certain
M.,
Sang.
among
H.
by
1951.
preparative
C. : Simple
for
Tomasi,
chains.
C.,
tannic
93:107,
C. : Zone
C.
A., and
istics
5:577,
enzymatic
antibodies.
Med.
Anal.
Huntley,
26.
papain,
Harboe,
H.
Biochem.
mon,
IgG
pepsin,
Anti-y-globulin
1963.
14. Williams,
R.
T. C., Jr. : Variations
tional
24.
Meth.
studies
human
K.,
of
with
hemagglutination
nation. Pediatrics 31:123,
Mallory,
Immunochemistry
C.
adsorption
treated
J. Clin.
Scand.
micromethod
serological
fractionated
Osterland,
The
subsequent
121:101,
13.
in
and
25.
1968.
of
acid
charac-
1965.
with
V. :
1960.
and
N.,
S.
on erythrocytes
phoresis.
“anti-anti-
serum
Curry,
bromelin.
Woz-
Fudenberg,
I. Hydrolysis
and
with
Identification
M.,
of
and
Boyden,
proteins
antiprotein
sera. J. Exp.
23. M#{252}ller-Eberhard,
porting
medium
for
1956.
new
J. Immunol.
terizition.
ficin
sera
B. :
reProc.
1964.
S.,
1:172,
W.
F.
rabbits.
1’.
proteins
52:60,
Human
Mandy,
of
factors.
Dubiski,
Sang.
Lewis,
normal
Jones
U.S.A.
F.,
Vox
11.
and
Bence
Milgrom,
body”.
Jr. : Heterogeneity
anti-y-globulin
Acad.
10.
C.,
WILLIAMS
(in press).
22.
9.
AND
G.
H.
significance
and
of
in
trans-
1969.
F.,
and
Horton,
isoantibody
stimulation
group-active
bacteria.
1280,
A.,
spe&ficity
1969.
R.
in
J.
E.:
man
Clin.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1970 36: 390-398
Naturally Occurring Human Antibodies to Pepsin-digested IgA
I. D. WILSON, R. D. SOLTIS and R. C. WILLIAMS, JR.
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