Soluble CD14 in cerebrospinal fluid in HIV sensory neuropathy.

Type: Poster
Title: Soluble CD14 in cerebrospinal fluid in HIV sensory neuropathy.
Authors: Ellis R, Gelman B, Letendre S, Clifford D, Marra C, McArthur J, McCutchan J,Simpson D, Grant I, and the CHARTER Group
Date: 03-05-2012
Abstract:Background: No reliable biomarker exists for HIV sensory neuropathy (SN), a condition associated with pain and disability that persists despite virologic suppression among individuals who are aging on long-­‐term combination antiretroviral therapy (CART). Chronic monocyte activation, particularly involving the dorsal root ganglia (DRG), may contribute to the persistence of HIV-­‐SN. Since soluble CD14 (sCD14) is shed by activated monocytes, we hypothesized that levels of sCD14 in cerebrospinal fluid (CSF) might be elevated in HIV-­‐SN. Methods: We selected 78 HIV+ virally suppressed (plasma VL<50 c/mL) individuals who had CSF sCD14 levels measured in CHARTER, a multicenter study of neurological disease and CART. HIV-­‐SN was defined by two or more of the following neuropathy signs: bilateral distal lower extremity reduced (or absent) vibration or sharp sensation or ankle reflexes. Neuropathy symptoms were bilateral, distal neuropathic pain, paresthesias or numbness. To evaluate the specificity of associations with sCD14, we also analyzed another marker of inflammation, soluble TNF receptor-­‐type 2 (sTNFR2). Both sCD14 and sTNFR2 were measured in CSF by commercially available ELISA. For parametric analysis, biomarker values were log10-­‐transformed, normalizing their distributions. Results: Subjects were 86% men, 44% non-­‐white, mean age 42 years (range 22-­‐61), median [IQR] nadir and current CD4 170 [50, 272] and 535 [349,694]. Twenty-­‐four (32%) had HIV-­‐SN, including 14 with neuropathic pain. Older age was associated with higher CSF sCD14 levels (r = 0.31; p=0.006). CSF sCD14 levels were higher in those with HIV-­‐SN (mean (±SD) log10 CSF sCD14 5.2(0.18) vs. 5.0(0.24); p=0.007; Cohen’s d = 0.71) and in those who reported neuropathic pain regardless of neuropathy signs (5.1(0.21) vs 5.0(0.24); p=0.04). Statistical adjustment for age attenuated, but did not eliminate, the relationship between HIV-­‐SN and sCD14, which remained significant after adjusting for other significant correlates of SN, including d-­‐drug use and nadir CD4. By comparison, CSF levels of sTNFR2 were not related to HIV-­‐SN. Conclusions: Elevated CSF levels of sCD14, but not sTNFR2, in aging persons with HIV-­‐SN on virally suppressive CART may reflect persistent monocyte activation, possibly producing injury to sensory neurons in DRG.