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Susceptibility to acute rheumatic fever based on differential expression of genes involved in cytotoxicity, chemotaxis, and apoptosis.
[acute rheumatic fever]
It
is
unknown
why
only
some
individuals
are
susceptible
to
acute
rheumatic
fever
(
ARF
)
.
We
investigated
whether
there
are
differences
in
the
immune
response
,
detectable
by
gene
expression
,
between
individuals
who
are
susceptible
to
ARF
and
those
who
are
not
.
Peripheral
blood
mononuclear
cells
(
PBMCs
)
from
15
ARF-susceptible
and
10
nonsusceptible
(
control
)
adults
were
stimulated
with
rheumatogenic
(
Rh
+
)
group
A
streptococci
(
GAS
)
or
nonrheumatogenic
(
Rh-
)
GAS
.
RNA
from
stimulated
PBMCs
from
each
subject
was
cohybridized
with
RNA
from
unstimulated
PBMCs
on
oligonucleotide
arrays
to
compare
gene
expression
.
Thirty
-
four
genes
were
significantly
differentially
expressed
between
ARF-susceptible
and
control
groups
after
stimulation
with
Rh
+
GAS
.
A
total
of
982
genes
were
differentially
expressed
between
Rh
+
GAS
-
and
Rh-
GAS
-stimulated
samples
from
ARF-susceptible
individuals
.
Thirteen
genes
were
differentially
expressed
in
the
same
direction
(
predominantly
decreased
)
between
the
two
study
groups
and
between
the
two
stimulation
conditions
,
giving
a
strong
indication
of
their
involvement
.
Seven
of
these
were
immune
response
genes
involved
in
cytotoxicity
,
chemotaxis
,
and
apoptosis
.
There
was
variability
in
the
degree
of
expression
change
between
individuals
.
The
high
proportion
of
differentially
expressed
apoptotic
and
immune
response
genes
supports
the
current
model
of
autoimmune
and
cytokine
dysregulation
in
ARF
.
This
study
also
raises
the
possibility
that
a
"
failed
"
immune
response
,
involving
decreased
expression
of
cytotoxic
and
apoptotic
genes
,
contributes
to
the
immunopathogenesis
of
ARF
.
Diseases
Validation
Diseases presenting
"peripheral blood mononuclear cells"
symptom
acute rheumatic fever
allergic bronchopulmonary aspergillosis
cohen syndrome
liposarcoma
malignant atrophic papulosis
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