From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
High
Titer
Anti-HIV
Antibody
in a Homosexual
By Valerie
L. Ng,
Kou
M. Hwang,
observed
infected
a
(ARC)
who
protein
had
a serum
gIL.
globulin
This
spike,
patient
serum,
been
and
and
p24.
shown
to
purified
this
performance
tite
had
were
of 1 :500.000.
gpl
Because
of lgG
2O.
in the
against
specific
tested
activity.
purified
The
antibody
activity
recognized
to
we
high
for
to
Recently,
a subset
of AIDS
contain
oligoclonal
and/or
teins.2’7
These
patients
with
but were
as multiple
tions,
such
were
paraproteins
Kaposi’s
dilution
sera
of
found
Infectious
from
meningitis,
domonal
acute
some
implicate
stimulus
driving
specific
the
antigen
might
presence
be directed
against
that
determine
and/or
an
of
B cell
whether
and
extrinsic
antigenic
found
lymphoma
sub-
nature
of
infections
antigenic
However,
to date,
no
has been directly
impli-
HIV
are
in HIV-infected
whether
HIV
frequency
with
Pseu-
infection,
We
paraproteins
in
at a relatively
would
of a clonal B cell process.
In this communication
an HIV infected
homosexual
male with AIDS
high
be the product
we describe
related
com-
plex (ARC)
who had a serum
globulin
level of 80 g/L.
Serum
protein
electrophoresis
(SPEP)
revealed
a gamma
globulin
fraction
of 40 g/L, of which
20 g/L was contained
within
an
mance
liquid
Blood,
IgG
kappa
paraprotein
chromatography
Vol 71, No
5 (May),
spike.
(HPLC)
1988:
pp
1397-1401
The
purified
serum,
to
Kd).
and
a p24-
“pol”
anti-
rearrangement
analy-
contained
population
conclude
the
this
15%
of immuno-
that
of
that
Affinity
using
(which
most
and
33
this
patient’s
anti-HIV
activity
paraprotein
was
not
in origin.
by Grune
& Stratton, Inc.
most
of the
total
anti-HIV
antibody
blot reactivity)
that his purified
activity
(as
present in his serum.
paraprotein
was not
in origin.
monoclonal
AND
METHODS
Case history.
RM is a 20-year-old
homosexual
white man who
presented
November
1985, with a I-year history of fatigue, lymphadenopathy,
and intermittent
night sweats. Physical examination
revealed
oral hairy leukoplakia
and diffuse
lymphadenopathy.
A
chest x-ray was unremarkable.
Laboratory
abnormalities
included a
hemoglobin
of 1 1.9 g/dL, a platelet count of 58,000/ML,
an erythrocyte sedimentation
rate of 103 mm/h,
a total serum protein of 1 12
g/L, and a globulin
level of75 g/L. He was also HBSAg positive and
HIV senopositive.
His serum
anti-HIV
antibodies
reacted
with
gpl2O”,
p66”, p55616, p53POl,
p4l6,
and p241’t (as determined
by
Western
blot), and was reactive to a final dilution of I :500,000
(data
not shown). SPEP revealed a polyclonal
hypengammaglobulinemia,
on which was superimposed
a protein
spike migrating
cathodal
to the
application
site. Densitometric
scanning
(not shown) revealed
that
his paraprotein
accounted
for approximately
50% of his gamma
globulin
fraction.
Immunofixation
electrophoresis
(IFE)
demonstrated
that the panaprotein
was comprised
predominantly
of IgG
From
non-transient
individuals,
we also wished
to
induced
the production
of parapro-
such
We
for
that
immuno-
two
“gag”
a clonal
not
parapro-
for the presence
of a B
Because
high-grade
occurs
in whole
a 1988
determinants.
to be
require
an evaluation
(ie, multiple
myeloma).
non-Hodgkin’s
para-
these
transient
paraproteinemias.
whether
an AIDS-associated
Paraproteinemias
nature
generally
cell malignancy
transient
individuals
syphilis,
The transient
with these
production.
of antigens
cells.
accounted
present
the
aspirate
to reveal
producing
30
gene
MATERIALS
infec-
B cell process
responsible
for
and
cytomegalovirus
their
or set
in causing
to determine
cated
wished
teins
benign
sclerosing
panencephalitis.9”4
of the paraproteins
associated
strongly
tein
associated
disease
marrow
failed
AIDS
opportunistic
have been observed
in sera from
toxoplasmosis,
malaria,
congenital
bone
wt
least
paraprotein
separated
determined
by Western
We also demonstrated
induction
of these paraproteins
is unclear
but may be related
to polyclonal
B cell activation
and aberrant
B cell immunoregulation
following
HIV infection.8’22’24
proteins
congenital
globulin
(Mol
Immunoglobulin
cells)
demonstrated
at
purified
gene
might
sulfate-polyacryl-
(SDS-PAGE)
the
“pol”
parapro-
in sera
not associated
with a clonal
myeloma.
The mechanism
a
contained
been
have
monoclonal
and with
sarcoma
of
plasma
dodecyl
contained
matrix
activities.
Sodium
and
paraprotein
p4la#{149}S,and
p53P0,
patient
4B
‘gag”
purified
species
of
monoclonal
EARLY
manifestation
of infection
with the human
immunodeficiency
virus (HIV)
is hypergammaglobulinemia,
often accompanied
by high titer anti-HIV
antibody
found
chain
paraprotein
N
activity.’
light
chromatography
sis
have
paraprotein
a final
p66#{176}’.p55.
paraprotein
body
paraprotein
purified
electrophoresis
p53PO
past
Spike
Khayam-Bashi,
both
the
in origin.
gel
Sepharose
antigens.
of
that
purified
dilution
using
a modified
(HPLC)-hydroxylapa-
the
the
Hassan
recognition
suggested
globulin
in his
p66#{176}’.p55.
D. Kaplan,
The
amide
a
kappa.
at a final
paraproteins
directed
fraction
a Paraprotein
Complex
S. McGrath
be monoclonal
within
antibodies
reactive
patient’s
paraprotein
liquid
chromatography
and
globulin
Lawrence
Michael
products
Serum
contained
anti-HIV
recognized
anti-HIV
1 :100.000.
was
titer
blot
antibody
retained
a gamma
gIL)
gIL.
With
Related
p24.
complex
80
predominantly
high
and
of
and
(HIV)-
related
level
Western
be
procedure
anti-HIV
(20
comprised
also
which
p41
50%
R. Reyes,
Hadley,
virus
AIDS
revealed
of which
paraprotein
with
AIDS
Keith
immunodeficiency
male
electrophoresis
of 40
A
human
homosexual
Associated
With
Gregory
w.
We
Reactivity
Male
high
perfor-
paraprotein
the Division
Medicine,
Inc.
Redwood
by
A124289-0I,
San
19. 1987;
National
Project
Society
Address
Career
Hospital;
The publication
payment.
“advertisement”
indicate
© 1988
L.D.K.
of Laboratory
Hospital;
GeneLabs,
San
Medicine,
Francisco,
CA
costs
ofthis
article
This
article
must
in
accordance
4. 1988.
Health
Award,
to Valerie
of
January
of
Grant
is a recipient
Development
requests
Department
General
Department
General
accepted
Institutes
111-2.
reprint
Activities,
Activities,
Francisco
CA.
August
Supported
Cancer
and
City,
Submitted
charge
ofAIDS
UCSF,
with
of
No.
L. Ng,
No.
P01
American
00087-96.
PhD.
UCSF
an
Division
and
San
of AIDS
Francisco
94! JO.
were
defrayed
therefore
18
U.S.C.
in part
be hereby
§1 734
by page
marked
solely
to
this fact.
by Grune
& Stratton.
Inc.
0006-4971/88/71O5-0028$3.O0/O
1397
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1398
NG El AL
with
serum
g/L
(4.23 to I 6.85 g/L), an IgA level of 2. 19 g/L (0.69 to 3.82 g/L), and
an 1gM level of 161 g/L
(0.63 to 2.77 g/L).
A urine
protein
electrophoresis
of a 200x concentrated
random urine specimen
(total
protein of 17 mg/dL)
revealed a faint protein
band in the betagamma
region, which consisted of free kappa chains.
Evaluation
of a
bone marrow
aspirate was remarkable
for a mild plasmacytosis
(10%
to 15% of cellular
elements),
without
any features
of plasma
cell
atypia.
The bone marrow
biopsy showed a slightly
hypercellular
marrow
(80% cellularity)
and a mild plasmacytosis.
No organisms
were
recovered
from bacterial,
mycobacterial,
or fungal cultures
of
blood
or bone marrow.
The patient
has remained
clinically
stable
since his initial presentation.
The abnormal
SPEP findings seen on
presentation
were still present when he was last evaluated
in January
kappa,
immunoglobulin
trace
amounts
of IgG
measurements
lambda.
revealed
an
Quantitative
IgG
level
of
and
SPEP
71
SPEPs and IFEs were performed
IFE.
as previously
described,’5
blot analysis.
Western blots
were performed
according
to the
for Disease Control
(CDC) immunoblot
were purified
from H9/HTLV-IIIB
cell
Western
reactivity
previously
described.
‘
HPLC-hyroxylapatite
plasma
final
(50
paraprotein
zL) were
concentration
to detect HIV serologic
December
1986, Centers
procedure.’6
HIV virions
culture supernatants
as
precipitated
of 19%
(wt/vol).
purification.
Proteins
by the addition
of Na2SO4
The
precipitate
was
from
to a
dialyzed
CaC12,
column
for
Bio-Rad Laboratories, Richmond,
CA).’8
Proteins
were eluted with a linear gradient
of 0.01 to 0.30 mol/L
Na-phosphate
(volume
30 to 50 mL), 10
zmol/L
CaCI,, at 1 mL/min,
with continuous
monitoring
of the
extensively
6.5,
22
24
against
001
mol/L
10 j.tmol/L
Na-phosphate,
and applied
to an HPLC-hydroxylapatite
monoclonal
antibody purification
(MAPS system;
1987.
pH
A
0
c”J
O
O
FractionNumber
2
4
6
8
10
12
14
16
18
20
26
28
30
32
34
36
38
40
42
44
0,
-65
B
-55
-25
C
20092
-
6845-
30-
Fig 1 . HPLC-hydroxylapatite
column
purification
of the paraprotein
spike.
(A) Densitometric
scan of column
fractions.
(B) Anti-HIV
reactivity
of individual
column fractions,
as determined
by Western
blot. The primary
reactive
protein
species include p66#{176}’.
p55.
p53.
and p24’9.
Fraction
24 retained
anti-HIV
reactivity
to a dilution
of 1 :100. (C) Coomassie
Blue-stained
SDS-PAGE
analysis
of column
fractions
1 9 to 31 . Molecular
weights,
expressed
in kilodaltons.
are as indicated
on the ordinates
of panels B and C.
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
PARAPROTEIN-ASSOCIATED
HIGH-TITER
ANTI-HIV
ANTIBODIES
1399
at 280 nm. The peak HPLC-hydroxylapatite
column fraction of interest was concentrated
80-fold (Amicon
CS 1 5 concentraton; Amicon Corp. Danvers, MA), and analyzed by IFE.
effluent
Sodium
dodecyl
sulfate
polyacrylamide
SDS-PAGE
(SDS-PAGE).
was
gel
performed
A
electrophoresis
as
previously
B
de-
scribed.’9
C
of anti-p24
antibodies,
CNBr
acti4B beads (Pharmacia)
were coupled
to 50 zg of
purified
recombinant
HIV p24 (generous
gift of C. Debouck,
Smith
Kline and French
Laboratories,
Swedeland,
PA) at a final concentration of 200 jg p24/mL
of beads using the methods published in
the Pharmacia
package
insert. These p24-Sepharose
beads were
incubated
with the HPLC-hydroxylapatite
column fraction of interest for 24 hours at 4#{176}C
with constant
agitation.
The supennatant
(containing
unbound
material)
was removed,
the beads washed ten
times with phosphate
buffered
saline, pH 7.5, and bound antibody
eluted with 3 mol/L
NaSCN.
Cell
lines.
The CEM cell line (T cell ALL)
and the EBV
transformed
B cell line, LB2, were grown in RPMI
1640 supplemented with 10% fetal calf serum.
P24
vated
affinity
purification
Sepharose
Southern
blot
analysis
for
immunoglobulin
(.1,,) gene
rearrange-
Mononuclear
cells were isolated from an EDTA-anticoagulated bone marrow
aspirate,
obtained after informed
consent according to the University
of California,
San Francisco
Human
Subjects
Committee
guidelines,
by Ficoll-hypaque
density gradient
centnifugation. DNA extraction
from 2 x lO RM bone marrow cells, CEM
cells and LB2
cells, HindIII
and EcoRl
double endonuclease
digestion,
nitrocellulose
transfer,
and H probe hybridization
were all
ment.
performed
as
of
the
paraprotein
chromatography
was
blot
Western
body
activity
(Fig
I B).
The
anode
used
to purify
the
paraprotein
RM.
Figure
lA shows
eluted
from an HPLC
Na2504
precipitate
analysis
activity
reactivity
that
showed
co-migrated
with this
eluted
protein
peak,
anti-HIV
antibody
not shown).
This
Fig 2.
Identification
reactive
of them
might
(Fig
(Mol
polyclonal
fraction
present
as
Fraction
spike
in the
peak
24.
bone
that a
column
of RM
anti-HIV
Figure
that
3 shows a Southern
gene probe of DNA
H
marrow
(lane
an established
to show a clonal immunothey were producing
the
been expected
rearrangement
if
have
gene
3) compared
T cell
line,
with
CEM
(lane
blot analysis
with an
extracted
from RM
DNA
extracted
1), and from
from
an EBV
Kb
anti-
9.6-
4.4-
as well
of this
individual
fraction
column
two
2.3-
fractions
of an immunoglobulin
as at least
was
heavy
different
sizes
of
of gamma
globulins),
we concentrated
24 and analyzed
it by IFE (Fig 2). The protein
in this fraction
had identical
electrophoretic
mobility
the paraprotein
(Figure
Southern
123
D).
clonality.
To address
the
we obtained
a sample
of patient
RM’s bone
cells and analyzed
the cellular
DNA
mononuclear
population
RM bone
2, lane
of the paraprotein
of clonality,
marrow
by
fraction.
light chain species (Mol wt 30 to 33 kd).
we had purified
the paraprotein
(and not a
assortment
Analysis
issue
the presence
wt 50 kd)
immunoglobulin
To verify
paraprotein
exhibiting
anti-HIV
reactivity
to a 1 :100 dilution.
was concentrated
BOx and analyzed
by IFE. SPEP analysis
of lane A. Dade control
serum;
lane B. RM’s
serum;
lane C, RM’s serum,
diluted
1 :10. IFE analysis
of BOx
concentrated
fraction
24 reacted
with antisera
directed
against
lane D. lgG (gamma)
heavy chain; lane E. 1gM (mu) heavy chain;
lane F, IgA (alpha) heavy chain.
peak of eluted
protein
fraction
24, contained
reactivity
of the
analysis
1 C) revealed
chain
of the
column
to a final dilution
of 1:100 (data
was directed
primarily
at HIV
the corrected
applied,
1:100,000.
SDS-PAGE
(-)
anti-HIV
“gag”
(p24, p4l, PSS) and “pol”
(p53, p66) gene products.
Because
the column
introduces
a dilutional
factor
of 1,000
when compared
with the original
starting
volume
of the
sample
cathode
(+)
paraprotein.
immunoglobulin
HPLC-hydroxy-
spike.
from the plasma
of patient
single
major
peak of protein
loaded
with
a 19% (wt/vol)
plasma.
F
globulin
RESULTS
lapatite
E
described.20
previously
Purification
D
blot
hybridization
of immunoglobulin
marrow
mononuclear
for
evidence
of
a clonal
producing
cells. Since 1 5% of
cells were plasma
cells, half
Fig 3.
Southern
blot analysis
of RM bone
marrow
mononurearrangement
(H)#{149} Ten
micrograms
of extacted
DNA was applied to each lane. Lane I,
CEM cells, an established
T cell line; lane 2. LB2 cells, a B cell
clone;
lane 3, RM bone marrow.
Relative
molcular
sizes are
expressed
in kilobases
(kb).
clear
cells
for
immunoglobulin
gene
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
NG El AL
1400
infected
and
DNA
immortalized
from
extracted
configuration
with hybridizing
The
DNA
biallelic
of
B cell
CEM
cells
clone,
non-rearranged
DNA
fragments
extracted
immunoglobulin
from
LB2
(lane
demonstrated
2). The
the germline
immunoglobulin
present
at 2.0 and
the B cell
rearrangement,
clone
with
genes,
3.0 kb.
conclusion
that
sis, our
level
sufficient
demonstrated
two hybridiz-
However,
plc
demonstrating
of B cells.
paraprotein
could
tion.
Previous
the absence
been
the
produced
clonal
from
antibodies
tope.
Yet,
body
reactivity
products
(“gag”
other
than
recognize
purified
against
at
and
population
if of clonal
a site
should
patient’s
this
of a clonal
paraprotein,
origin,
that
only
paraprotein
least
“pol”).
two
We
affinity
was
“gag”
“pol”
antibody
reactivity
antibody
reactivity
of this
“gag”
polyclonal
nature
of antigen
recognition.
(Fig
epi-
contained
anti-
HIV
gene
purified
anti-p24
(HPLC-hydroxylaissue of whether
recognizing
a common
and “pol”
gene products
being comprised
of a polyclonal
ies. Figure
4 shows that we
Mono-
antigenic
different
antibodies
from the purified
paraprotein
patite
column
fraction
24) to address
the
paraprotein
between
biopsied.
one
have
the
group
of anti-HIV
could
separate
the
antibodanti-HIV
4, lane
anti-HIV
(Fig 4, lane
“paraprotein”
A) from
the
B), demonstrating
by the heterogeneity
The observation
that
transient
paraproteinemias
were seen
with infectious
diseases9”4
suggested
that a
antigenic
stimulus
was responsible
for the production
immunoglobulins.
The purpose
of this study was to
association
specific
of such
the antigenic
investigate
seen
We
have
of
the
activity
that this
anti-HIV
patient’s
serum.
The
species in the purified
reactivity
against
if any,
against
paraprotein
antibody
multiple
HIV
present
“pol”
for
in this
of at least two light chain
fraction,
and the antigenic
HIV
from
have
out
the
coupled
with
the
likelihood
that
this
a monoclonal
documented
B cell
B cell
polyclonal
suggesting
that
a
gene
products,
support
the
Kd
6655-
following
HIV
accompanied
manifestation
vigorous
by
of
and
response
occurs at the time of infection.
from
our study
of this patient
that
intact
We would
a vigorous
giving
the appearance
of a paraprotein.
A paraprotein
is defined
an abnormal
immunoglobulin
by current
laboratory
methods
as
that migrates
as a single band
and is composed
species
of a single
observed
previously
patients
definition
in AIDS
of heavy
and light
methods,
by immunologic
and
was comprised
monoclonal
not available
sary
ARC
chains.
chains had
are the
have been
patients
(ie,
in those
disease attributable
to HIV)2’7;
the
of these paraproteins
was made
with advanced
of monoclonality
in which
the paraprotein(s)
were
IgG kappa)
only. The data
however,
that a paraprotein
predominantly
of IgG
was not of
kappa
origin.
Sophisticated
laboratory
studies,
usually
to the routine
clinical
laboratory,
were neces-
to disprove
monoclonality.
mdi-
Because the finding
of paraproteins
in HIVinfected
viduals
is not infrequent,
we recommend
that
laboratory
evaluation
of
is seen
clinical
and
laboratory
nancy
is not
a
hypercalcemia,
bone
marrow)
for
However,
pathologic
the
full
be stratified-if
patients
evaluation
necessary.
of
such
in the setting
of a polyclonal
in an HIV-infected
patient,
paraprotein
maglobulinemia
suggestive
41-
popula-
B cell activa-
immunoregulation
Hypergammaglobulinemia
antibody
titers is an early
infection,’
been
clone.
multi-
anti-HIV
antibody
response
was still present,
but was atypical in that the majority
of his anti-HIV
antibodies
were of a
similar
charge,
such that they migrated
in a tight band on
that
paraprotein
“gag”
and
alone accounted
reactivity
observation
paraprotein
rules
shown to be of one class (usually
presented
in this study showed,
of a paraprotein
individual
with ARC.
that this particular
demonstrated
contained
anti-HIV
gene products,
and
most
specificity,
an HIV-infected
in
derived
studies
immune
conclude
in
not have
The restricted
expression
of the immunoglobulin
led to the prevailing
concept
that
paraproteins
products
of single
clones
of B cells. Paraproteins
DISCUSSION
in
monoclonal
may
determinants
chains
defective
infection.8’22’24
high anti-HIV
SPEP,
the
not
presence
of a minor
B cell
this paraprotein
recognized
antigenic
light
two
was
and
HIV
epitope
shared
v the paraprotein
HIV
of
was
sensitivity
of hybridization
discrete
presence
tion
paraprotein
we did not detect
a clonal
B cell population
bone marrow
by immunoglobulin
gene analy-
to rule out the
the finding
that
able DNA
fragments
present at I .8 kb. The DNA
extracted
from RM’s
bone marrow
showed
a germline
configuration
However,
this
origin.
Although
in the patient’s
a plasma
if
other
monoclonal
lytic bone lesions,
atypical
are present,
then a full
a
hypergamthen further
cell
malig-
clinical
signs
(ie,
gammopathy
plasma
evaluation
cells
in the
is war-
ranted.
24-
In other
a
ciation
transiently
with
disappeared
infection
AB
Fig 4.
Affinity
purification
of anti-p24
antibodies
and
Western
blot analysis
of antibody
reactivity.
Affinity
purification
was performed
as described
in Materials
and Methods.
Lane A, Peak HPLC
fraction
#24 reactivity
(input);
lane B. Affinity
purified
antibody
from peak HPLC fraction
#24.
Molecular
weights.
expressed
in
kilodaltons.
are indicated
on the ordinate.
with
is
this
expect
various
expressed
resolution
a chronic
patient’s
of the
life-long
paraprotein
for the remainder
of his lifetime.
the continued
expression
of this
years after the
infection
would
oligoclonal
AIDS
and
patients.2’7
paraproteins
diseases,
infectious
initial
also
disease.
In fact,
paraprotein
in asso-
paraproteins
However,
infection;
thus,
to be continually
observation.
explain
the
monoclonal
seen
the
HIV
we would
expressed
we have observed
for at least 1.5
The chronicity
of HIV
continued
observance
of
paraproteins
in other
ARC
and
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
PARAPROTEIN-ASSOCIATED
HIGH-TITER
ANII-HIV
ANTIBODIES
1401
It is intriguing
to speculate
on the origin
of high grade
B
cell lymphomas
in the AIDS
population
in light of this study.
One study2’
demonstrated
the presence
of multiple
mono-
already
at the stage of expanded
multiple
B cell clones,
and
that another
event will trigger
the selective
expansion
of one
of these clones
to result
in lymphoma.
We are currently
clonal B cell populations
syndrome
(LAS)
and
following
patients
with
present.
This
B cell
sary
lymphoma
suggested
instrumental
in
event
another
the
one
Perhaps
of
although
expansion
of
in c-myc
the
expanded
infection
multiple
B cell
B cell
clones
who
have
up
our
patient
and
with paraproteins
of B cell lymphomas
other
similarly
HIV
infected
to see if there
is an increased
within
this population.
was
ACKNOWLEDGMENT
We gratefully
presumably
already
patients
incidence
clones,
was neces-
of lymphoma,
patients
gene
c-myc
HIV
rearrangement)
development
HIV-infected
lymphadenopathy
only
in AIDS
was a rearranged
that
(resulting
for the ultimate
from
in patients
with
AIDS.
However,
present.
paraproteins
are
acknowledge
the helpful suggestions
and Dan Stites; the technical assistance of Katherine
Kane,
Marilyn
Weeks,
Jane Marsh,
and Peter
secretarial
assistance
of Sandra Gumpert.
ofC.S. Chiang
Chen, Debora
Ryan;
and the
REFERENCES
1 . Nath N, Wunderlich
C, Darr FW III, Douglas DK, Dodd
Immunoglobulin
level in donor blood reactive
for antibodies
human immunodeficiency
virus. J Clin Microbiol
25:364, 1987
2. Heniot
K, Hallquist
AE, Tomar
RH: Panaproteinemia
patients
with
acquired
immunodeficiency
syndrome
RY:
to
in
(AIDS)
or
lymphadenopathy
syndrome
(LAS). Clin Chem 31:1224,
1985
3. Papadopoulos
NM, Lane HC, Costello R, Moutsopoulos
HM,
Masur H, Gelmann EP, Fauci AS: Oligoclonal
immunoglobulins
in
patients
with the acquired
immunodeficiency
syndrome.
Clin
Immunol
Immunopathol
35:43, 1985
4. Costello
R, Papadopoulos
NM: Oligoclonal
banding
in hypergammaglobulinemia.
Clin Chem 33:905, 1987 (abstr)
5. Papadopoulos
in healthy
immunodeficiency
6. Deutsch
Costello
and
R: Oligoclonal
heterosexual
Brown
immunoglobulins
exposed to human
1987 (abstr)
couples
virus. Clin Chem 33:905,
M,
characterization
with HIV
Washington,
NM,
homosexual
MA,
of oligoclonal
antibodies.
Third
DC, 1987 (abstn
Repetti
CF: The frequency
and
protein (OCP)
bands in individuals
International
Conference
on AIDS,
MP.l 14)
Bnatt G, Waldenlind
L, von Knogh G, Karlsson
A, Mobeng L,
Sandstrom
E: Oligoclonal
IgG bands on serum-electrophoresis
in a
cohort of homosexual
men in Stockholm,
Sweden.
Third Intennational
Conference
on AIDS,
Washington,
DC,
1987 (abstr
THP. 130)
7.
8. Lane HC, Masur H, Edgar LC, Whalen G, Rook AH, Fauci
AS: Abnormalities
of B cell activation
and immunoregulation
in
patients with the acquired immunodeficiency
syndrome.
N Engl J
Med 309:453, 1983
9. Ritzmann SE: Immunoglobulin
abnormalities,
in Ritzmann
Daniel JC (eds): Serum
Protein
Abnormalities,
Diagnostic
Clinical
Aspects.
Boston, Little, Brown and Co. 1975, p 463
10. Seligmann
myeloma
globulins.
1 1 . Weinberg
Monoclonal
Pediatrics
12.
AG,
McCracken
macroglobulinemia
51:518,
Griscelli
toxoplasmosis.
M, Brouet
JC:
Semin Hematol
Antibody
activity
10:163, 1973
of
5,
and
human
GH, LoSpalluto
J, Luby GP:
and cytomegalic
inclusion
disease.
1973
C, Desmonts
G, Gny
J Pediatr 83:20, 1973
B, Frommel
D: Congenital
13. Potter M: Myeloma
proteins (M-components)
with antibodylike activity. N Engl J Med 284:831,
1971
I 4. Seligmann
M, Clauvel J-P: Current views on immunoglobulin
abnormalities
and B cell prolifenations.
Adv Nephrol
7:237, 1978
15. Gerard
5K, Chen
KH,
Khayam-Bashi
H: 1gM-kappalambda biclonal gammopathy
elucidated
by immunofixation
dcctrophonesis.
Diag Immunol
4:155, 1986
16. Tsang VCW, Hancock
K, Wilson M, Palmer DF, Whaley 5,
McDougal
JS, Kennedy
5: Enzyme-linked
immunoelectnophoresis
blot technique
(EITB) (Western
Blot) for HTLV-IIl/LAV
antibodies. Immunology
series No. 1 15, US Department
of Health
and
Human Services,
1986
I 7. McGrath
MS, Witte
0, Pincus T, Weissman
IL: Retrovirus
purification:
Method
which conserves envelope glycoprotein
and
maximizes
infectivity.
J Vinol 25:923, 1978
18. Stanker
LH, Vanderlaan
M, Juarez-Salinas
H: One step
purification
of mouse monoclonal
antibodies
from ascites fluid by
hydroxylapatite
chromatography.
J Immunol
Methods
76:157,
1985
19. Laemmli
UK: Cleavage of structural
proteins
during
the
assembly
of the head of bacteriophage
T4. Nature 277:680,
1970
20. Maniatis
T, Fnitsch E, Sambrook
I: Molecular
Cloning.
Cold
Spring Harbor,
NY, Cold Spring Harbor
Laboratory,
1982
21. Pelicci P-G, Knowles
DM II, Arlin ZA, Wieczorek
R, Luciw
P, Dma D, Basilico
C, Dalla-Favera
R: Multiple
monoclonal
B cell
expansions
and c-myc oncogene
rearrangements
in acquired
immune
deficiency
syndrome-related
lymphoproliferative
disorders.
J Exp
Med 164:2049, 1986
22. Yarchoan
R, Redfield
RR, Broder 5: Mechanisms
of B cell
activation
in patients
with acquired
immunodeficiency
syndrome
and related disorders. J Clin Invest 78:439, 1986
23. Binx DL, Redfield
RR, Tosato
G: Defective
regulation
of
Epstein-Barr
virus infection
in patients
with acquired
immunodeficiency syndrome
(AIDS)
on AIDS-related
disorders.
N EngI J Med
314:874,
1986
Pahwa 5G. Quilop MTJ, Lange M, Pahwa RN, Gnieco MH:
Defective
B-lymphocyte
function
in homosexual
men in relation
to
the acquired
immunodeficiency
syndrome.
Ann
Intern
Med
24.
101:757,
1984
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1988 71: 1397-1401
High titer anti-HIV antibody reactivity associated with a paraprotein spike in
a homosexual male with AIDS related complex
VL Ng, KM Hwang, GR Reyes, LD Kaplan, H Khayam-Bashi, WK Hadley and MS McGrath
Updated information and services can be found at:
http://www.bloodjournal.org/content/71/5/1397.full.html
Articles on similar topics can be found in the following Blood collections
Information about reproducing this article in parts or in its entirety may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#repub_requests
Information about ordering reprints may be found online at:
http://www.bloodjournal.org/site/misc/rights.xhtml#reprints
Information about subscriptions and ASH membership may be found online at:
http://www.bloodjournal.org/site/subscriptions/index.xhtml
Blood (print ISSN 0006-4971, online ISSN 1528-0020), is published weekly by the American Society of
Hematology, 2021 L St, NW, Suite 900, Washington DC 20036.
Copyright 2011 by The American Society of Hematology; all rights reserved.