DNA BREAKS DETECTED BY IN-SITU END-LABELING IN DORSAL-ROOT GANGLIA OFPATIENTS WITH AIDS

Distal sensory axonal polyneuropathy (DSP) is the most frequent HIV-as sociated peripheral neuropathy. DSPs tend to occur in full-blown AIDS and worsen as CD4 cell counts decrease in blood. To assess a possible role for apoptosis in the pathogenesis of the neuropathy, we used in s itu end-labelling (ISEL) detecting DNA strand breaks in DRG neurons of 19 HIV-infected patients, of whom nine had axonal polyneuropathy, and 11 controls. Sensory neurons with ISEL-assessed DNA breaks were obser ved in 9/19 patients with AIDS, 0/3 patients with pre-AIDS, and 1/11 c ontrols. The prevalence of DNA breaks in neurons was higher in AIDS pa tients than in controls (P < 0.05). Among AIDS patients, DNA breaks in neurons were more abundant in patients with peripheral neuropathy (P < 0.04). It is possible that DNA breaks of DRG neurons induce the axon opathy and consequently play a role in the pathogenesis of DSP. It can not be excluded, however, that DNA breaks could represent the result r ather than the cause of axonopathy. We suggest that ISEL may detect ne urons that were primed to apoptosis before death in relation with the HIV infection, and undergo DNA fragmentation at time of death, rather than neurons that underwent premortem both priming and triggering step s of the apoptotic process. This hypothesis could explain why most ISE L-positive neurons lack typical apoptotic morphology and why normal co ntrols do not show ISEL positive cells.