P18-19. CSF levels of the glial marker YKL-40 are strongly associated with neuronal injury in HIV

Linn Hermansson [1], Aylin Yilmaz [1], Markus Axelsson [2], Kaj Blennow [3], Dietmar Fuchs [4], Lars Hagberg [1], Jan Lycke [2], Henrik Zetterberg [3,5], Magnus Gisslén [1]
Affiliates: [1] Dpt of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [2] Dpt of Neurology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [3] Dpt of Psychiatry and Neurochemistry , Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. [4] Division of Biological Chemistry, Biocenter, Innsbruck Medical University, Innsbruck, Austria. [5] Institute of Neurology, University College London, UK.

Background
HIV-1 infects the central nervous system (CNS) shortly after transmission. This leads to a chronic intrathecal immune activation. YKL-40 is a biomarker that reflects activation of astroglial cells, previously not thoroughly investigated in relation to HIV. The objective of this study was to characterize cerebrospinal fluid (CSF) YKL-40 in chronic HIV infection, with and without antiretroviral treatment (ART).

Methods
YKL-40, neopterin (marker of monocyte/macrophage activation), and the neuronal marker neurofilament light protein (NFL) were analyzed with ELISA in archived CSF samples from 120 HIV-infected (85 untreated neurological asymptomatic (NA) patients; 7 with HIV associated dementia (HAD); and 28 on effective ART), and 39 HIV-negative controls.

Results
YKL-40 was significantly higher in HAD compared to all other groups, but was also higher in untreated NA patients with CD4 350 and persons on ART did not have significantly different CSF YKL-40 levels compared to controls. Significant correlations were found between CSF YKL-40 and age (r=0.38, p<0.001), CD4 (r=-0.36, p<0.001), plasma HIV-RNA (r=0.35, p<0.001), CSF HIV-RNA (r=0.35, p<0.001), CSF neopterin (r=0.40, p<0.001), albumin ratio (r=0.44, p<0.001), and CSF NFL (r=0.71, p<0.001). Age, CD4, albumin ratio, and CSF HIV RNA were found as independent predictors of CSF YKL-40 concentrations in a multivariable analysis. CSF YKL-40 was shown to be a strong independent predictor of CSF NFL in a multivariable analysis, together with age, CSF neopterin, and CD4 cell count.

Conclusions
This study suggests that CSF YKL-40 could be a valuable marker in understanding HIV neuropathogenesis. The strong correlation between CSF YKL-40 and NFL supports a pathogenetic association between astroglial activation and neuronal injury and suggests the utility of further exploring the prognostic value of YKL-40.