Sunday, July 29, 2012
Beta Glucans Experience Increased Immune Function Naturally.
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7:43 AM
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betablucans,
betaglucan,
betaglucan immune,
glucan,
glucans,
immune
History of (103)-b-D-glucans testing
Lehmann and Reiss were the first to report the
measurement of circulatingAspergillus fumigatusanti-gen in rabbits and humans with IA in 1978 [16].
Theirstrategy involved the development of an antiserum
against serum from rabbits experimentally infected with
A. fumigatus. They detected a single antigenic moiety
that circulated in the blood of infected rabbits and
humans with proven IA [16]. They later determined
that galactomannan was the molecule being detected
by the rabbit antiserum [17].
During these experiments,
Betaglucans was isolated and characterized fromA. fumigatus
cell walls, but found to be non-antigenic [17].
In 1968, Levin and Bang developed an assay for
bacterial endotoxin using the amebocytes ofLimulus
polyphemus[the American horseshoe crab] [18]. During
pyrogenicity testing of carboxy-methylated Betaglucans that was
being studied as an anti-tumor agent, Kakinuma and
colleagues noted that Betaglucans consistently turned theLimu-lus test positive
, despite confirmation of non-pyrogeni-city in inoculated animals [19].
Morita and colleagues, by
studying Tachypleus tridentatus [Japanese horseshoe
crab] amebocyte lysate fractions, demonstrated that
Betaglucans triggered theLimulustest coagulation cascade via
a separate proenzyme, which was termed Factor G (Fig.
1) [20].
Obayashi and colleagues developed a chromo-genic test based on the recombination of the different
amebocyte lysate fractions and proposed that use of
recombined fractions containing Factor G, but not
Factor C, which recognizes endotoxin, could be used
for non-invasive testing for the diagnosis of invasive
fungal diseases (IFD) [21].
Following proof of principle
studies [22] and after confirmation that Betaglucans was indeed
the substrate that bound to Factor G to trigger the
reaction cascade of their chromogenic test [23], Obayashi
and colleagues published the first multicenter validation
study in 1995 [11].
A similar Betaglucans test was developed using
amebocyte lysate fractions of the American horseshoe
crab and approved by the FDA in 2004 as an aid in the
diagnosis of fungemia and deep-seated mycoses [24]
following a prospective validation study [12]
Role of (103)-b-D-glucan in the diagnosis of invasive aspergillosis
Measurement of serum (103)-b-D-Glucan (Betaglucans) is an aid in the diagnosis of
fungemia and deep-seated mycoses, including invasive aspergillosis (IA). Betaglucans is
present in the cell wall of most pathogenic fungi (includingPneumocystis jiroveci)
in significant amounts with some notable exceptions such as Cryptococcus
neoformans and Zygomycetes.
Commercially available assays can detect serum
Betaglucans concentrations as low as 1 pg/mL. Published validation studies have included
patients with IA and other invasive fungal diseases (IFD). Betaglucans detection appears to
be more sensitive than galactomannan detection in patients with IA, but Betaglucans’s
intrinsic lack of mycological specificity requires the integration of clinical,
radiological, and microbiological data for proper interpretation. Betaglucans assay test
characteristics can be used, for example, to exclude IA in some clinical scenarios
, to increase the certainty of IA in the presence of an isolated positive galactomannan
result or when testing follows initiation of antifungal treatment. Betaglucans may be falsely
elevated in the serum in the absence of IFD in patients undergoing hemodialysis
with cellulose membranes, in patients treated with immunoglobulin, albumin, or
other blood products filtered through cellulose filters containing Betaglucans, and in
patients with serosal exposure to glucan-containing gauze or to certain intravenous
antimicrobials.
These potential sources of false positivity should be considered
when interpreting Betaglucans results. Betaglucans may be useful as a sensitive screening tool for
surveillance of IA and other IFD in populations at risk. Stratified IFD screening
and diagnostic strategies using both galactomannan and Betaglucans should be explored.
Factors affecting the production and clearance of Betaglucans during IA and other IFD
need additional study to further refine its diagnostic utility.
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