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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
"fever"
symptom
22q11.2 deletion syndrome
acute rheumatic fever
alexander disease
allergic bronchopulmonary aspergillosis
canavan disease
carcinoma of the gallbladder
child syndrome
congenital toxoplasmosis
cushing syndrome
cystinuria
dracunculiasis
erdheim-chester disease
esophageal adenocarcinoma
esophageal carcinoma
familial mediterranean fever
focal myositis
hodgkin lymphoma, classical
lamellar ichthyosis
legionellosis
locked-in syndrome
malignant atrophic papulosis
neonatal adrenoleukodystrophy
neuralgic amyotrophy
oculocutaneous albinism
papillon-lefèvre syndrome
pyomyositis
pyruvate dehydrogenase deficiency
scrub typhus
severe combined immunodeficiency
sneddon syndrome
systemic capillary leak syndrome
triple a syndrome
typhoid
waldenström macroglobulinemia
wolf-hirschhorn syndrome
This symptom has already been validated