The FASEB Journal,
Journal Year:
2023,
Volume and Issue:
37(11)
Published: Oct. 12, 2023
The
complement
system
is
a
complex,
tightly
regulated
protein
cascade
involved
in
pathogen
defense
and
the
pathogenesis
of
several
diseases.
Thus,
development
modulators
has
risen
as
potential
treatment
for
complement-driven
inflammatory
pathologies.
enzymatically
inactive
MAP-2
been
reported
to
inhibit
lectin
pathway
by
competing
with
its
homologous
serine
protease
MASP-2.
membrane-bound
inhibitor
CD55
acts
on
C3/C5
convertase
level.
Here,
we
fused
four
N-terminal
domains
generating
targeted
chimeric
modulate
activation
at
two
different
levels
cascade.
Its
biological
properties
were
compared
vitro
parent
molecules.
While
alone
showed
minor
inhibition
three
pathways
when
co-incubated
serum
(IC50MAP-2+CD551-4
=
60.98,
36.10,
97.01
nM
classical,
lectin,
alternative
pathways,
respectively),
MAP-2:CD551-4
demonstrated
potent
inhibitory
activity
(IC50MAP-2:CD551-4
2.94,
1.76,
12.86
nM,
respectively).
This
was
substantially
enhanced
pre-complexes
formed
recognition
molecule
mannose-binding
0.14
nM).
also
effective
protecting
sensitized
sheep
erythrocytes
classical
hemolytic
assay
(CH50
13.35
Finally,
reduced
neutrophil
full
blood
after
stimulation
Aspergillus
fumigatus
conidia,
well
phagocytosis
conidia
isolated
activated
neutrophils.
Our
results
demonstrate
that
reinforcing
idea
engineered
fusion
proteins
are
promising
design
strategy
identifying
developing
drug
candidates
treat
complement-mediated
Journal of Clinical Investigation,
Journal Year:
2024,
Volume and Issue:
134(9)
Published: April 30, 2024
Careful
regulation
of
the
complement
system
is
critical
for
enabling
proteins
to
titrate
immune
defense
while
also
preventing
collateral
tissue
damage
from
poorly
controlled
inflammation.
In
eye,
this
balance
between
activity
and
inhibition
crucial,
as
a
low
level
basal
necessary
support
ocular
privilege,
prerequisite
maintaining
vision.
Dysregulated
activation
contributes
parainflammation,
inflammation
triggered
by
cellular
that
functions
reestablish
homeostasis,
or
outright
disrupts
visual
axis.
Complement
dysregulation
has
been
implicated
in
many
diseases,
including
glaucoma,
diabetic
retinopathy,
age-related
macular
degeneration
(AMD).
last
two
decades,
focus
intense
investigation
AMD
pathogenesis,
leading
development
novel
therapeutics
treatment
atrophic
AMD.
This
Review
outlines
recent
advances
challenges,
highlighting
therapeutic
approaches
have
advanced
clinical
trials,
well
providing
general
overview
posterior
segment
eye
selected
diseases.
Respiratory Research,
Journal Year:
2024,
Volume and Issue:
25(1)
Published: Jan. 4, 2024
Abstract
Background
The
complement
system
is
an
important
arm
of
immune
defense
bringing
innate
and
adaptive
immunity.
Although
originally
regarded
as
a
major
complementary
mechanism
against
pathogens,
continuously
emerging
evidence
has
uncovered
central
role
this
complex
in
several
diseases
including
lung
pathologies.
Main
body
Complement
factors
such
anaphylatoxins
C3a
C5a,
their
receptors
C3aR,
C5aR
C5aR2
well
inhibitory
proteins
CD55,
CD46
CD59
have
been
implicated
pathologies
the
acute
respiratory
distress
syndrome,
pneumonia,
chronic
obstructive
pulmonary
disease,
asthma,
interstitial
diseases,
cancer.
However,
exact
mechanisms
by
which
induce
these
remain
unclear.
Several
complement-targeting
monoclonal
antibodies
are
reported
to
treat
diseases.
Conclusions
contributes
progression
Better
understanding
underlying
will
provide
groundwork
develop
new
strategy
target
for
treatment
Frontiers in Immunology,
Journal Year:
2023,
Volume and Issue:
14
Published: Sept. 11, 2023
The
complement
system
plays
crucial
roles
in
a
wide
breadth
of
immune
and
inflammatory
processes
is
frequently
cited
as
an
etiological
or
aggravating
factor
many
human
diseases,
from
asthma
to
cancer.
Complement
receptors
encompass
at
least
eight
proteins
four
structural
classes,
orchestrating
complement-mediated
humoral
cellular
effector
responses
coordinating
the
complex
cross-talk
between
innate
adaptive
immunity.
progressive
increase
understanding
features
main
factors,
activated
proteolytic
fragments,
their
assemblies
have
spurred
renewed
interest
deciphering
receptor
complexes.
In
this
review,
we
describe
what
currently
known
about
biology
complexes
with
natural
agonists
pharmacological
antagonists.
We
highlight
fundamental
concepts
gray
areas
where
issues
problems
been
identified,
including
current
research
gaps.
seek
offer
guidance
into
information
underlies
therapeutic
endeavors.
Finally,
also
indicate
believe
are
potential
developments
field.
European Journal of Immunology,
Journal Year:
2024,
Volume and Issue:
54(12)
Published: Sept. 12, 2024
Therapeutic
interventions
in
the
complement
system,
a
key
immune-inflammatory
mediator
and
contributor
to
broad
range
of
clinical
conditions,
have
long
been
considered
important
yet
challenging
or
even
unfeasible
achieve.
Almost
20
years
ago,
spark
was
lit
demonstrating
commercial
viability
complement-targeted
therapies.
Since
then,
field
has
experienced
an
impressive
expansion
targeted
indications
available
treatment
modalities.
Currently,
dozen
distinct
complement-specific
therapeutics
covering
several
intervention
points
are
clinic,
benefiting
patients
suffering
from
eight
disorders,
not
counting
numerous
trials
off-label
uses.
Observing
this
rapid
rise
therapy
obscurity
mainstream
with
amazement,
one
might
ask
whether
peak
development
now
reached
will
continue
marching
on
new
heights.
This
review
looks
at
milestones
drug
discovery
achieved
so
far,
surveys
currently
approved
entities
indications,
ventures
glimpse
into
future
advancements
come.
European Journal of Immunology,
Journal Year:
2024,
Volume and Issue:
54(11)
Published: Aug. 27, 2024
Abstract
Infections
are
one
of
the
most
significant
healthcare
and
economic
burdens
across
world
as
underscored
by
recent
coronavirus
pandemic.
Moreover,
with
increasing
incidence
antimicrobial
resistance,
there
is
an
urgent
need
to
better
understand
host–pathogen
interactions
design
effective
treatment
strategies.
The
complement
system
a
key
arsenal
host
defense
response
pathogens
bridges
both
innate
adaptive
immunity.
However,
in
contest
between
mechanisms,
not
always
victorious.
Pathogens
have
evolved
several
approaches,
including
co‐opting
regulators
evade
complement‐mediated
killing.
Furthermore,
deficiencies
proteins,
genetic
therapeutic,
can
lead
inefficient
pathogen
eradication,
rendering
more
susceptible
certain
infections.
On
other
hand,
overwhelming
infection
provoke
fulminant
activation
uncontrolled
inflammation
potentially
fatal
tissue
organ
damage.
This
review
presents
overview
critical
aspects
complement‐pathogen
during
discusses
perspectives
on
designing
therapies
mitigate
dysfunction
limit
injury.
World Journal of Hepatology,
Journal Year:
2025,
Volume and Issue:
17(3)
Published: March 25, 2025
The
complement
system
is
crucial
for
maintaining
immunological
homeostasis
in
the
liver,
playing
a
significant
role
both
innate
and
adaptive
immune
responses.
Dysregulation
of
this
closely
linked
to
pathogenesis
various
liver
diseases.
Modulating
can
affect
progression
these
conditions.
To
provide
insights
into
treating
injury
by
targeting
regulation
system,
we
conducted
comprehensive
search
major
biomedical
databases,
including
MEDLINE,
PubMed,
EMBASE,
Web
Science,
identify
articles
on
reviewed
functions
mechanisms
injury.
Kidney International,
Journal Year:
2023,
Volume and Issue:
105(1), P. 177 - 188
Published: Nov. 3, 2023
Activation
of
the
alternative
pathway
(AP)
complement
is
involved
in
pathogenesis
antineutrophil
cytoplasmic
antibody
(ANCA)-associated
vasculitis
(AAV),
although
underlying
molecular
mechanisms
are
unclear.
To
gain
insight
into
role
AP,
common
gene
variants
CFH/CFHR1-5,
CFB,
C3
and
MCP,
longitudinal
determinations
plasma
C3,
C4,
FH,
FHR-1,
FHR-2,
FHR-5,
FB,
properdin
sC5b-9
levels
were
analyzed
a
Spanish
AAV
cohort
consisting
102
patients;
54
with
active
(active
cohort)
48
remission
not
receiving
immunosuppressants
or
dialysis
therapy
(remission
cohort).
The
validation
consisted
100
patients
ANCA-associated
glomerulonephritis.
Here,
we
demonstrated
that
genetic
components
AP
associated
disease
susceptibility
(CFB32Q/W)
severity
kidney
damage
(CFH-H1,
CFH1H2
ΔCFHR3/1).
Plasma
significantly
different
between
cohorts.
In
observations,
high
degree
activation
at
diagnosis
was
worse
outcome,
while
basal
FHR-1
lower
FH/FHR-1
ratios
determined
severe
forms
AAV.
These
plasmatic
findings
confirmed
cohort.
Additionally,
autoantibodies
against
FH
convertase
identified
one
five
patients,
respectively.
Thus,
our
study
key
determine
susceptibility,
prognosis,
Our
data
also
suggests
balance
critical
supports
as
novel
AP-specific
therapeutic
target
