| 1. |
- Jiang, Wei, et al.
(författare)
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Cerebrospinal fluid and plasma lipopolysaccharide (LPS) levels in HIV-1 infection and associations with inflammation, blood-brain barrier permeability and neuronal injury.
- 2021
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Ingår i: The Journal of infectious diseases. - : Oxford University Press (OUP). - 1537-6613 .- 0022-1899. ; 223:9, s. 1612-1620
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Tidskriftsartikel (refereegranskat)abstract
- HIV infection is associated with increased systemic microbial translocation, neuro-inflammation and occasionally neuronal injury. Whether systemic LPS penetrates into the brain and contributes to neuro-inflammation remain unknown in HIV. Here, we measured plasma and cerebrospinal fluid (CSF) LPS levels along with biomarkers of neuro-inflammation (white blood cell counts and 40 soluble markers) and neurofilament light chain (NfL). Notably, CSF LPS was undetectable in all samples, including three HIV-infected individuals with dementia. Increased plasma LPS, neuro-inflammation, and blood-brain barrier (BBB) dysfunction were found in untreated HIV-infected individuals, but not in healthy or treated HIV-infected individuals. Plasma LPS levels were directly correlated with various markers of inflammation in both plasma and CSF, as well as with degree of BBB permeability but not with CSF NfL in HIV-infected subjects. These results suggest that the magnitude of microbial translocation associates with neuro-inflammation and BBB permeability in HIV without direct penetration into the central nervous system (CNS).
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| 2. |
- Peluso, Michael J, et al.
(författare)
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Cerebrospinal fluid soluble CD30 elevation despite suppressive antiretroviral therapy in individuals living with HIV-1.
- 2020
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Ingår i: Journal of virus eradication. - 2055-6640. ; 6:1, s. 19-26
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Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to assess soluble CD30 (sCD30), a protein that colocalises with HIV-1 RNA and DNA in lymphoid cells and tissues, in cerebrospinal fluid (CSF) as a marker of HIV-1 infection in the central nervous system (CNS).This was a cross-sectional study using archived samples from two clinical cohorts. Soluble CD30 concentrations were measured in paired CSF and plasma from untreated viraemic individuals (n=52), individuals on suppressive antiretroviral therapy (ART) (n=33), HIV-1 controllers (n=10), participants with CSF HIV-1 'escape' (n=11) and controls without HIV-1 infection (n=16). Nonparametric tests were used to compare levels across groups and evaluate correlations with HIV-1 RNA, CSF neurofilament light chain protein (NFL) and neopterin.Compared with controls (median 30ng/mL, interquartile range [IRQ] 23-50), plasma sCD30 levels were elevated in viraemic participants (75ng/mL, 52-116; P<0.001), but not in those on suppressive ART (38ng/mL, 32-62). In contrast, CSF sCD30 levels were elevated in ART-suppressed individuals (34ng/mL, 19-46; P=0.001) and in those with CSF 'escape' (33ng/mL, 27-40; P=0.004) compared with controls (18ng/mL, 11-23), but not in untreated viraemic individuals. No association was observed between CSF sCD30 and plasma HIV-1 RNA, concurrent or nadir CD4+ T cell count, duration of infection or plasma sCD30. CSF sCD30 correlated with CSF NFL (r=0.34, P=0.001).In contrast to plasma, sCD30 levels are elevated in the CSF of individuals with HIV-1 infection who are on suppressive ART. Elevated levels of sCD30 in the CSF may be an indicator of persistent CNS HIV-1 infection, although the mechanism underlying this elevation warrants further investigation.
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