al., 2001; Ablij and Meinders, 2002; Volanakis, 1982).
Human C-Reactive Protein (hCRP) is a highly
conserved acute phase protein that is synthesised
in the liver as a response to infection, inflammation
and tissue damage (Volanakis and Kaplan, 1971).
It is a part of the pentraxin protein family, making
up the short pentraxin sub group along with serum
amyloid P (SAP). Pentraxins has an important role in
the innate immune system that involves recognising
the foreign molecules and activating the immune
system (Martinez de la Torre et al., 2010). In body, in
addition to activating the complement system, hCRP
is responsible for recognising pathogens, and clearing
the apoptotic and necrotic cells. Therefore, it is said
to be restoring the function and structure of tissues
(Gershov, et al., 2000; Volanakis, 2001). Meanwhile, in
clinical settings, the amount of infection in the body
is quantified by the level hCRP of found in the blood
(Pepys and Hirschfield, 2003).
hCRP in Clinical Settings and the Synthesis of CRP
CRP was initially discovered by Tillet and Francis
in 1930 where they initially named the protein as
‘Fragment C’ since it was the third fraction that was
derived from the pneumococci (Tillett and Francis,
1930). Although Tillett and Francis (1930) recognised
that hCRP is not limited to pneumococcal infections,
it was only later found that it is synthesised in the
liver in response to inflammatory stimuli, where the
synthesis is induced by interleukin-1 and interleukin-6
(Hurlimann et al., 1966; Kushner, et al., 1995).
The production of hCRP is highly dependent on the
amount of infection in the body since it can rapidly
increase depending on the severity of the infection
and inflammation in the body, hence making it an
acute-phase protein (Pepys and Hirschfield, 2003). A
healthy young adult would normally have 0.8mg of
hCRP in per litre of their blood (Shine et al., 1981).
However, it is known to increase up to 500mg per
litre as a result of acute-phase stimulus (Pepys and
Hirschfield, 2003). Rapid increase of circulating hCRP
concentration in response to acute-phase stimuli
and short plasma half-life, makes hCRP an excellent
non-specific biomarker in clinical settings (ibid).
Furthermore, recent studies suggest that, with the use
of high sensitivity immune-assays, it can also be used
as an early indicator of cardiovascular heart disease
(ibid). Meanwhile, Ridker et al., (2002) suggests that
using hCRP levels in combination with low density
lipoprotein levels in blood will show a more precise
prediction of cardiovascular diseases. Furthermore,
Lau et al., (2006) suggests a correlation between
CRP levels and Human immunodeficiency virus (HIV)
progression on top of associations with developing
cardiovascular diseases in HIV patients.
Pentraxin Protein Family and Conservation of CRP
C-Reactive Protein is a part of the Pentraxin protein
family (Gewurz et al., 1995). As it was mentioned
earlier, pentraxins play an important role in the
immune system where they recognise pathogens
in order to tag them which in turn activates the
complement system (Du Clos, 2013). Pentraxins
have sub-categories as short and long pentraxins;
Long pentraxins include proteins such as Pentraxin
3 (PTX3) and Pentraxin 4 (PTX4), while short
pentraxins involve ‘serum amyloid P’ (SAP) along
with CRP (Martinez de la Torre et al., 2010).
Structurally, pentraxins are made up of 5 to 10 sub
units arranged in a pentameric radial symmetry in
order to accommodate binding interactions with
various ligands such as polysaccharides in a calcium
dependent process (Gewurz et al., 1995)
Short pentraxins, have shorter amino acid sequence
compared to long pentraxins, while as shown in
figure 1, they are also less conserved. On the other
hand, CRP is known to be conserved throughout
evolution, from invertebrates to vertebrates, which
suggests the importance of the protein in innate
immune system. Long pentraxins, which have longer
amino acid sequences, can be categorised to have
a C-terminal and N-terminal in their amino acid
sequence. C-terminal is shown to have homology
with short pentraxins while the N-terminal needs
further investigation (Du Clos, 2013).
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