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2015 ; 2
(ä): ä Nephropedia Template TP
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English Wikipedia
Post-infectious inflammatory response syndrome (PIIRS): Dissociation of
T-cell-macrophage signaling in previously healthy individuals with cryptococcal
fungal meningoencephalitis
#MMPMID27064474
Williamson PR
Macrophage (Houst)
2015[]; 2
(ä): ä PMID27064474
show ga
Cryptococcus is an important cause of central nervous system infections in both
immunocompromised patients such as those with HIV/AIDS as well as previously
healthy individuals. Deficiencies in T-cell activation are well-known to be
highly associated with host susceptibility in HIV/AIDS as well in animal modeling
studies, resulting in poor microbiological control and little host inflammation.
However, recent studies conducted in human patients have demonstrated roles for
macrophage signaling defects as an important association with disease
susceptibility. For example, an autoantibody to granulocyte monocyte stimulating
factor (GMCSF) resulted in defective STAT5 signaling and susceptibility to
cryptococcosis. In addition, severe cases of cryptococcal meningo-encephalitis in
previously healthy patients, with or without anti-GMCSF autoantibody, developed a
highly activated intrathecal T-cell population but had defects in effective
macrophage polarization. Intrathecal inflammation correlated with neurological
damage, measured by the axonal damage protein, neurofilament light chain 1. Based
on these studies, we propose a new syndrome of cryptococcal post-infectious
inflammatory response syndrome (PIIRS) defined in previously healthy patients
with cryptococcal meningo-encephalitis as the presence of a poor clinical
response in the setting of at least 1 month of amphotericin-based fungicidal
therapy and sterile cerebrospinal cultures. These findings are discussed in light
of the potential for improving therapy.