DNA breaks detected by in situ end-labelling in dorsal root ganglia of patients with AIDS.
Distal sensory axonal polyneuropathy (DSP) is the most frequent HIV-associated 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 situ 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 observed in 9/19 patients with AIDS, 0/3 patients with pre-AIDS, and 1/11 controls. The prevalence of DNA breaks in neurons was higher in AIDS patients 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 axonopathy and consequently play a role in the pathogenesis of DSP. It cannot be excluded, however, that DNA breaks could represent the result rather than the cause of axonopathy. We suggest that ISEL may detect neurons 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 steps of the apoptotic process. This hypothesis could explain why most ISEL-positive neurons lack typical apoptotic morphology and why normal controls do not show ISEL positive cells.
Adle-Biassette
H
H
Département de Pathologie (Neuropathologie), CHU Henri Mondor, Créteil, France.
Bell
J E
JE
Creange
A
A
Sazdovitch
V
V
Authier
F J
FJ
Gray
F
F
Hauw
J J
JJ
Gherardi
R
R
D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology*; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D053938:DNA Fragmentation; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology / Q000821:virology*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000166:cytology* / Q000821:virology*; D011115:Polyneuropathies / Q000473:pathology / Q000821:virology