The diagnostic utility of elevation in cerebrospinal fluid β₂–microglobulin in HIV–1 dementia

We measured serum and CSF β2-microglobulin (β2M) levels in HIV-1 seropositive individuals with and without dementia to determine the frequency and diagnostic utility of elevation of CSF β32M. We compared 34 samples from 27 patients with HIV-1 dementia with 110 samples from 54 HIV-1 seropositive participants in the Multicenter AIDS Cohort Study, none of whom had progressive dementia. Neurosyphilis and CNS opportunistic processes were excluded in all subjects. We stratified the nondemented subjects by duration of HIV seropositivity and peripheral blood CD4 count. Compared with the nondemented group, demented subjects had significantly higher CSF total protein, IgG%, and CSF albumin/serum albumin ratios. A highly significant association was found between elevated CSF β2M and reduced CD4 count (p< 0.0001). No significant differences were noted between the demented and nondemented groups in CSF WBC count or in the frequency of CSF HIV-1 isolation. The mean CSF β2M was 1.9 mg/l in the nondemented subjects compared with 4.2 mg/l in those with dementia (p< 0.0001). We derived a cutoff of 3.8 mg/l from the distribution of CSF β2M in the nondemented group. The determination of CSF β2M had a sensitivity of 44%, specificity of 90%, and a positive predictive value of 88% for diagnosis of HIV dementia when compared with nondemented subjects with CD4 counts<200. In those without dementia, there was a strong correlation between serum and CSF β2M (r = 0.50, p< 0.0001), but in demented subjects CSF β2M was elevated independently of serum levels, suggesting that CSF β2M is produced within the brain in HIV dementia. In the absence of CNS opportunistic processes, elevated CSF β2M >3.8 mg/l is a clinically useful marker for HIV dementia.