Alzheimer s & Dementia,
Год журнала:
2024,
Номер
20(3), С. 2128 - 2142
Опубликована: Янв. 22, 2024
Abstract
INTRODUCTION
We
aimed
to
investigate
associations
between
common
infections
and
neuroimaging
markers
of
dementia
risk
(brain
volume,
hippocampal
white
matter
lesions)
across
three
population‐based
studies.
METHODS
tested
serology
measures
(pathogen
serostatus,
cumulative
burden,
continuous
antibody
responses)
outcomes
using
linear
regression,
including
adjustments
for
total
intracranial
volume
scanner/clinic
information
(basic
model),
age,
sex,
ethnicity,
education,
socioeconomic
position,
alcohol,
body
mass
index,
smoking
(fully
adjusted
model).
Interactions
apolipoprotein
E
(
APOE
)
genotype
were
tested.
Findings
meta‐analyzed
cohorts
N
main
=
2632;
APOE‐interaction
1810).
RESULTS
Seropositivity
John
Cunningham
virus
associated
with
smaller
brain
volumes
in
basic
models
(β
−3.89
mL
[−5.81,
−1.97],
P
<
0.05);
these
largely
attenuated
fully
−1.59
[−3.55,
0.36],
0.11).
No
other
relationships
robust
multiple
testing
corrections
sensitivity
analyses,
but
several
suggestive
observed.
DISCUSSION
did
not
find
clear
evidence
risk.
Some
findings
warrant
replication.
Cell Reports Medicine,
Год журнала:
2025,
Номер
unknown, С. 101946 - 101946
Опубликована: Фев. 1, 2025
Highlights•Sex
and
CMV
status
affect
baseline
immune
variation
but
not
YF17D
vaccine
outcomes•High
numbers
of
activated
CD4+
T
cells
at
link
to
stronger
responses•Elevated
CXCL10
levels
are
negatively
associated
with
responses•Environmental
factors
contribute
the
tied
responseSummaryThe
live-attenuated
yellow
fever
17D
(YF17D)
is
a
model
acute
viral
infection
that
induces
long-lasting
protective
immunity.
Among
immunocompetent
adults,
responses
vary
significantly.
To
understand
sources
this
variability,
we
investigate
influence
sex,
age,
human
leukocyte
antigen
(HLA)
type,
20
prior
infections
on
basal
parameters
cellular
antibody
response
in
250
healthy
young
individuals.
Multivariate
regression
found
sex
cytomegalovirus
(CMV)
significantly
do
except
for
reduced
YF17D-specific
CD8+
frequencies
CMV-infected
males.
However,
abundance
non-specific
cytokine-expressing
helper
circulation
responses,
state
smoking
favors.
Additionally,
an
elevated
level
interferon-stimulated
linked
poorer
vaccination
outcomes.
Altogether,
reactivity
conditioned
by
independent
CMV-related
variations.Graphical
abstract
ABSTRACT
The
dengue
viruses
(DENV)
envelope
(E)
protein
is
the
main
target
of
antibody
(Ab)
response.
Abs
different
epitopes
on
E-protein,
including
sE-dimer,
E
domain
III
(EDIII),
and
fusion
loop
(FL).
Anti-EDIII
are
mainly
serotype-specific,
whereas
anti-FL
can
induce
antibody-dependent
enhancement
(ADE)
in
vitro
.
targeting
sE-dimer
cross-neutralize
DENV
serotypes.
However,
involvement
each
Ab
subset
disease
pathogenicity
and/or
protection
remains
unclear.
We
aimed
to
optimize
quantification
purification
E-protein
epitope-specific
from
human
samples.
C-terminal
biotinylated
DENV2
recombinant
proteins
(EDIII,
soluble
[sE],
sE-dimer)
were
coupled
color-coded
magnetic
microspheres
for
a
multiplex
immunoassay
(MIA),
testing
antigen
concentrations.
Assay
performance
was
evaluated
using
well-characterized
anti-DENV
monoclonal
antibodies
(mAbs)
total
IgG
seronegative
seropositive
plasma.
Specific
FL
blocked
with
mouse
mAb
clone
4G2
quantify
anti-FL-
sE-dimer-specific
Abs,
measuring
antigen-antibody
reactions
as
median
fluorescence
intensity
(MFI).
For
isolation
antibodies,
sE-proteins
conjugated
streptavidin
resin
beads.
Total
plasma
incubated
immobilized
EDIII
elute
anti-EDIII
Abs.
flow-through
beads
specific
enriched
fraction,
applied
sE
In
conclusion,
we
have
developed
serological
assay
detect
DENV-infected
humans.
Additionally,
successfully
isolated
anti-EDIII,
anti-FL,
an
fraction
IMPORTANCE
development
effective
virus
vaccines
has
been
hampered
by
limited
insights
into
immunological
mechanisms
protection.
Our
study
addresses
this
gap
introducing
refined
microsphere-based
(MIA)
isolate
(Abs)
epitopes,
such
(FL),
This
method
provides
detailed
profiling
high
sensitivity
requires
minimal
sample
volumes.
ability
subsets
also
enables
investigations
their
roles
or
pathogenesis,
paving
way
more
interventions.
Human
papilloma
virus
infection
is
known
to
influence
oropharyngeal
cancer
(OPC)
risk,
likely
via
sexual
transmission.
However,
behaviour
has
been
correlated
with
other
risk
factors
including
smoking
and
alcohol,
meaning
independent
effects
are
difficult
establish.
We
aimed
evaluate
the
causal
effect
of
on
OPC
using
Mendelian
randomization
(MR).
Cells,
Год журнала:
2022,
Номер
11(22), С. 3619 - 3619
Опубликована: Ноя. 15, 2022
The
immune
pathogenesis
of
multiple
sclerosis
(MS)
is
thought
to
be
triggered
by
environmental
factors
in
individuals
with
an
unfavorable
genetic
predisposition.
Epstein-Barr
virus
(EBV)
infection
a
major
risk
factor
for
subsequent
development
MS.
Human
endogenous
retroviruses
(HERVs)
can
activated
EBV,
and
might
missing
link
between
initial
EBV
the
later
onset
In
this
study,
we
investigated
differential
gene
expression
patterns
EBV-immortalized
lymphoblastoid
B
cell
lines
(LCL)
from
MS-affected
(MSLCL)
controls
using
RNAseq
qRT-PCR.
data
LCL
mapped
human
genome
virtual
metagenome
were
used
identify
possible
biomarkers
MS
or
disease-relevant
factors,
e.g.,
relapse
rate.
We
observed
that
lytic
EBNA-1
transcripts
seemed
negatively
correlated
age
leading
increased
younger
PBMC
donors.
Further,
HERV-K
(HML-2)
GAG
was
upon
EBV-triggered
immortalization.
Besides
well-known
transactivation
HERV-K18,
our
results
suggest
another
six
HERV
loci
are
up-regulated
stimulation
EBV.
identified
differentially
expressed
genes
MSLCL,
several
loci,
ERVMER61-1
ERV3-1,
as
well
associated
relapses.
summary,
induces
suitable
risk.
International Journal of Epidemiology,
Год журнала:
2023,
Номер
52(4), С. 1197 - 1208
Опубликована: Март 13, 2023
Abstract
Background
Helicobacter
pylori
infection
is
a
major
cause
of
non-cardia
gastric
cancer
(NCGC),
but
uncertainty
remains
about
the
associations
between
sero-positivity
to
different
H.
antigens
and
risk
NCGC
cardia
(CGC)
in
populations.
Methods
A
case-cohort
study
China
included
∼500
each
incident
CGC
cases
∼2000
subcohort
participants.
Sero-positivity
12
was
measured
baseline
plasma
samples
using
multiplex
assay.
Hazard
ratios
(HRs)
for
marker
were
estimated
Cox
regression.
These
further
meta-analysed
with
studies
same
Results
In
subcohort,
varied
from
11.4%
(HpaA)
70.8%
(CagA).
Overall,
10
showed
significant
(adjusted
HRs:
1.33
4.15),
four
(HRs:
1.50
2.34).
After
simultaneous
adjustment
other
antigens,
positive
remained
(CagA,
HP1564,
HP0305)
HyuA).
Compared
CagA
sero-positive
only
individuals,
those
who
all
three
had
an
adjusted
HR
5.59
(95%
CI
4.68–6.66)
2.17
1.54–3.05)
CGC.
meta-analysis
NCGC,
pooled
relative
2.96
2.58–3.41)
[Europeans:
5.32
4.05–6.99);
Asians:
2.41
2.05–2.83);
Pheterogeneity<0.0001].
Similar
pronounced
population
differences
also
evident
GroEL,
HcpC
HP0305.
meta-analyses
CGC,
two
HP1564)
significantly
associated
higher
Asians
not
Europeans.
Conclusions
several
increased
varying
effects
Asian
European
Frontiers in Immunology,
Год журнала:
2023,
Номер
14
Опубликована: Дек. 19, 2023
Introduction
Epstein-Barr
virus
(EBV)
infection
in
humans
is
associated
with
a
wide
range
of
diseases
including
malignancies
different
origins,
most
prominently
B
cells.
Several
EBV
latent
genes
are
thought
to
act
together
cell
immortalization,
but
minimal
set
sufficient
for
transformation
remains
be
identified.
Methods
Here,
we
addressed
this
question
by
transducing
human
peripheral
cells
from
EBV-negative
donors
retrovirus
expressing
the
encoding
Latent
Membrane
Protein
(LMP)
1
and
2A
Nuclear
Antigen
(EBNA)
2.
Results
LMP1
EBNA2,
not
alone
or
combination
LMP2A
was
able
transform
primary
LMP1/EBNA2-immortalized
lines
shared
surface
markers
EBV-transformed
lymphoblastoid
(LCLs).
They
showed
sustained
growth
more
than
60
days,
albeit
at
lower
rate
LCLs.
generated
tumors
when
transplanted
subcutaneously
into
severely
immunodeficient
NOG
mice.
Conclusion
Our
results
identify
proteins
transformation.
Brain Communications,
Год журнала:
2024,
Номер
6(2)
Опубликована: Янв. 1, 2024
Abstract
Persistent
infections,
whether
viral,
bacterial
or
parasitic,
including
Helicobacter
pylori
infection,
have
been
implicated
in
non-communicable
diseases,
dementia
and
other
neurodegenerative
diseases.
In
this
cross-sectional
study,
data
on
635
cognitively
normal
participants
from
the
UK
Biobank
study
(2006–21,
age
range:
40–70
years)
were
used
to
examine
H.
seropositivity
(e.g.
presence
of
antibodies),
serointensities
five
antigens
a
measure
total
persistent
infection
burden
associated
with
selected
brain
volumetric
structural
MRI
(total,
white,
grey
matter,
frontal
matter
(left/right),
white
hyperintensity
as
percent
intracranial
volume
bi-lateral
sub-cortical
volumes)
diffusion-weighted
measures
(global
tract-specific
fractional
anisotropy
mean
diffusivity),
after
an
average
9–10
years
lag
time.
was
calculated
cumulative
score
for
over
20
different
pathogens.
Multivariable-adjusted
linear
regression
analyses
conducted,
whereby
potential
confounders
(all
measures)
(sub-cortical
adjusted,
stratification
by
Alzheimer’s
disease
polygenic
risk
tertile
when
exposures
antigen
serointensities.
Type
I
error
adjusted
0.007.
We
report
little
evidence
association
between
various
outcomes
(P
>
0.007,
multivariable
models),
unlike
previously
reported
past
research.
However,
serointensities,
particularly
immunoglobulin
G
against
vacuolating
cytotoxin
A,
GroEL
outer
membrane
protein
antigens,
poorer
integrity
<
0.007),
serointensity
linked
worse
cognition-related
tracts
such
external
capsule,
anterior
limb
internal
capsule
cingulum,
specifically
at
low
risk.
Vacuolating
A
greater
among
individuals
mid-level
risk,
while
highest
urease
consistently
reduced
caudate
volumes
right
putamen
0.007).
Outer
larger
left
nucleus
accumbens)
middle
levels
Our
results
shed
light
relationship
seropositivity,
measures.
These
are
important
given
links
infectious
agents
disease,
can
be
development
drugs
preventive
interventions
that
would
reduce
those
