692 OTK18: A Surrogate Marker for HIV-1 Associated Dementia K. Carlson*, I. Kadiu, G. Pohlman, T. Biskup, H. Gendelman, J. Limoges Univ of Nebraska Med Ctr, Omaha
Background:OTK18 was revealed utilizing differential display of RNA from HIV-1-infected monocyte derived macrophages. This was done to assess macrophage secretory factors that influence the neuro destructive processes of HIV-1-associated dementia (HAD). Previously, OTK18 was found to be a transcriptional suppressor with anti-retroviral properties. It is expressed at high levels during HIV-1 encephalitis. Based on this, we hypothesized that OTK18 may serve as a predictive biomarker of neurologic disease associated with progressive HIV-1 infection.
Methods: To assess the relationship of OTK18 with HAD, archived plasma was obtained from the Univ of Nebraska Med Ctr from HIV-1-infected patients (pts) with/out HAD and uninfected controls. To correlate OTK18 with HAD prognosis, CD4 and viral load matched archived plasma samples were obtained from the California NeuroAIDS Tissue Consortium (CNTN) from HAD pts with/out neurologic improvement on study and HIV-1-infected non-demented controls. Total protein was prepared from each sample (n = 3/group), depleted of serum albumin and levels of peripheral OTK18 measured by antibody-capture utilizing an OTK18 polyclonal antibody and ProteinChip Technology. To calculate OTK18 concentration, a standard curve was generated using a 14.4 kDa synthetic OTK18 peptide. All data was tested for significance by student’s t-tests.
Results:OTK18 expression was higher in HIV-1 infected pts vs uninfected controls and highest from pts with HAD. In the CNTN group, we found that levels of OTK18 were significantly higher (p = 0.04) in the HAD stable/worse group compared to the HAD improved or non-demented control groups. There was no significant difference in OTK18 levels between the HAD improved or control patient samples. Notably, the CNTN samples were baseline study samples, prior to neurologic improvement or decline.
Conclusions:OTK18 levels were found to be highest in plasma from the most neurologically impaired pts. Interestingly, the baseline levels of OTK18 in HAD pts with neurologic improvement were the same as non-demented controls. Based on these findings, we preliminarily conclude that OTK18 may serve as a putative biomarker for either stage of disease or for disease susceptibility.
