Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Recombination-activating gene 1 (Rag1)-deficient mice with severe combined immunodeficiency treated with lentiviral gene therapy demonstrate autoimmune Omenn-like syndrome.
[omenn syndrome]
Recombination-activating
gene
1
(
RAG
1
)
deficiency
results
in
severe
combined
immunodeficiency
(
SCID
)
caused
by
a
complete
lack
of
T
and
B
lymphocytes
.
If
untreated
,
patients
succumb
to
recurrent
infections
.
We
sought
to
develop
lentiviral
gene
therapy
for
RAG
1
-
induced
SCID
and
to
test
its
safety
.
Constructs
containing
the
viral
spleen-focus-forming
virus
(
SF
)
,
ubiquitous
promoters
,
or
cell
type
-
restricted
promoters
driving
sequence-optimized
RAG
1
were
compared
for
efficacy
and
safety
in
sublethally
preconditioned
Rag
1
(
-
/
-
)
mice
undergoing
transplantation
with
transduced
bone
marrow
progenitors
.
Peripheral
blood
CD
3
(
+
)
T
-
cell
reconstitution
was
achieved
with
SF
,
ubiquitous
promoters
,
and
cell
type
-
restricted
promoters
but
3
-
to
18
-
fold
lower
than
that
seen
in
wild-
type
mice
,
and
with
a
compromised
CD
4
(
+
)
/
CD
8
(
+
)
ratio
.
Mitogen-mediated
T
-
cell
responses
and
T
cell-dependent
and
T
cell-independent
B-
cell
responses
were
not
restored
,
and
T
-
cell
receptor
patterns
were
skewed
.
Reconstitution
of
mature
peripheral
blood
B
cells
was
approximately
20
-
fold
less
for
the
SF
vector
than
in
wild-
type
mice
and
often
not
detectable
with
the
other
promoters
,
and
plasma
immunoglobulin
levels
were
abnormal
.
Two
months
after
transplantation
,
gene
therapy-treated
mice
had
rashes
with
cellular
tissue
infiltrates
,
activated
peripheral
blood
CD
44
(
+
)
CD
69
(
+
)
T
cells
,
high
plasma
IgE
levels
,
antibodies
against
double
-stranded
DNA
,
and
increased
B
cell-activating
factor
levels
.
Only
rather
high
SF
vector
copy
numbers
could
boost
T
-
and
B-
cell
reconstitution
,
but
mRNA
expression
levels
during
T
-
and
B-
cell
progenitor
stages
consistently
remained
less
than
wild-
type
levels
.
These
results
underline
that
further
development
is
required
for
improved
expression
to
successfully
treat
patients
with
RAG
1
-
induced
SCID
while
maintaining
low
vector
copy
numbers
and
minimizing
potential
risks
,
including
autoimmune
reactions
resembling
Omenn
syndrome
.
Diseases
Validation
Diseases presenting
"peripheral blood"
symptom
adrenomyeloneuropathy
allergic bronchopulmonary aspergillosis
aniridia
cohen syndrome
congenital toxoplasmosis
cutaneous mastocytosis
erdheim-chester disease
esophageal adenocarcinoma
esophageal squamous cell carcinoma
familial mediterranean fever
gm1 gangliosidosis
junctional epidermolysis bullosa
lamellar ichthyosis
monosomy 21
oligodontia
omenn syndrome
scrub typhus
severe combined immunodeficiency
typhoid
von hippel-lindau disease
waldenström macroglobulinemia
wiskott-aldrich syndrome
wolf-hirschhorn syndrome
x-linked adrenoleukodystrophy
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom