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Göteborgs universitets publikationer

Soluble CD14 in cerebrospinal fluid is associated with markers of inflammation and axonal damage in untreated HIV-infected patients: a retrospective cross-sectional study

Författare och institution:
S. Jespersen (-); K. K. Pedersen (-); Birgitta Anesten (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Henrik Zetterberg (Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi); D. Fuchs (-); Magnus Gisslén (Institutionen för biomedicin, avdelningen för infektionssjukdomar); Lars Hagberg (Institutionen för biomedicin, avdelningen för infektionssjukdomar); M. Troseid (-); S. D. Nielsen (-)
Publicerad i:
Bmc Infectious Diseases, 16 s. Article number: 176
ISSN:
1471-2334
Publikationstyp:
Artikel, refereegranskad vetenskaplig
Publiceringsår:
2016
Språk:
engelska
Fulltextlänk:
Sammanfattning (abstract):
Background: HIV-associated cognitive impairment has declined since the introduction of combination antiretroviral treatment (cART). However, milder forms of cognitive impairment persist. Inflammation in the cerebrospinal fluid (CSF) has been associated with cognitive impairment, and CSF neurofilament light chain protein (NFL) and CSF neopterin concentrations are increased in those patients. Microbial translocation in HIV infection has been suggested to contribute to chronic inflammation, and lipopolysaccharide (LPS) and soluble CD14 (sCD14) are markers of microbial translocation and the resulting monocyte activation, respectively. We hypothesised that microbial translocation contributes to inflammation and axonal damage in the central nervous system (CNS) in untreated HIV infection. Methods: We analyzed paired samples of plasma and CSF from 62 HIV-infected, untreated patients without cognitive symptoms from Sahlgrenska University Hospital, Gothenburg, Sweden. Measurements of neopterin and NFL in CSF were available from previous studies. Plasma and CSF sCD14 was measured using ELISA (R&D, Minneapolis, MN), and plasma and CSF LPS was measured using LAL colorimetric assay (Lonza, Walkersville, MD, USA). Univariate and multivariate regression analyses were performed. Results: LPS in plasma was associated with plasma sCD14 (r = 0.31, P = 0.015), and plasma sCD14 was associated with CSF sCD14 (r = 0.32, P = 0.012). Furthermore, CSF sCD14 was associated with NFL (r = 0.32, P = 0.031) and neopterin (r = 0.32, P = 0.012) in CSF. LPS was not detectable in CSF. In a multivariate regression model CSF sCD14 remained associated with NFL and neopterin after adjusting for age, CD4+ cell count, and HIV RNA in CSF. Conclusions: In a group of untreated, HIV-infected patients LPS was associated with sCD14 in plasma, and plasma sCD14 was associated CSF sCD14. CSF sCD14 were associated with markers of CNS inflammation and axonal damage. This suggest that microbial translocation might be a driver of systemic and CNS inflammation. However, LPS was not detectable in the CSF, and since sCD14 is a marker of monocyte activation sCD14 may be increased due to other causes than microbial translocation. Further studies regarding cognitive impairment and biomarkers are warranted to fully understand causality.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
MEDICIN OCH HÄLSOVETENSKAP ->
Klinisk medicin
Nyckelord:
HIV, CNS inflammation, Microbial translocation, sCD14, NFL, Neopterin, central-nervous-system, immunodeficiency-virus-infection, t-cell, depletion, combination antiretroviral therapy, blood-brain-barrier, microbial translocation, neurocognitive disorders, monocyte activation, immune activation, plasma-levels, Infectious Diseases
Postens nummer:
237125
Posten skapad:
2016-05-31 11:18
Posten ändrad:
2016-05-31 13:48

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