Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study.

BACKGROUND: Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the pathogenesis of HAND. METHODS: IgG antibodies against MOG were measured by ELISA in sera and cerebrospinal fluid (CSF) of 65 HIV-positive patients with HAND (n = 14), cerebral opportunistic infections (HIVOI, n = 25), primary HIV infection (HIVM, n = 5) and asymptomatic patients (HIVasy, n = 21). As control group HIV-negative patients with bacterial or viral CNS infections (OIND, n = 18) and other neurological diseases (OND, n = 22) were included. In a subset of HAND patients MOG antibodies were determined before and during antiviral therapy. RESULTS: In serum, significantly higher MOG antibody titers were observed in HAND compared to OND patients. In CSF, significantly higher antibody titers were observed in HAND and HIVOI patients compared to HIVasy and OND patients and in OIND compared to OND patients. CSF anti-MOG antibodies showed a high sensitivity and specificity (85.7% and 76.2%) for discriminating patients with active HAND from asymptomatic HIV patients. MOG immunopositive HAND patients performed significantly worse on the HIV dementia scale and showed higher viral load in CSF. In longitudinally studied HAND patients, sustained antibody response was noted despite successful clearance of viral RNA. CONCLUSIONS: Persistence of MOG antibodies despite viral clearance in a high percentage of HAND patients suggests ongoing neuroinflammation, possibly preventing recovery from HAND.

Methylation changes in faecal DNA: a marker for colorectal cancer screening?

DNA methylation is a common molecular alteration in colorectal cancer cells. We report an assessment of faecal DNA from patients with colorectal cancer and controls to determine the feasibility, sensitivity, and specificity of this approach. By use of MethyLight analysis of faecal DNA from three independent sets of patients, we identified SFRP2 methylation as a sensitive single DNA-based marker for identification of colorectal cancer in stool samples (sensitivity 90% [CI 56-100] and specificity 77% [46-95] in the training set [n=23]; sensitivity 77% [46-95] and specificity 77% [46-95] in an independent test set [n=26]). Whether a combination of genetic and epigenetic markers will identify colorectal cancer at an early stage remains to be shown.