Publications & Reports

Ex vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-associated sensory neuropathy.

Mountford J, Octaviana F, Estiasari R, Setiawan DD, Ariyanto I, Lee S, Gaff J, Chew C, Jackaman C, Kamerman P, Cherry C, Price P
School of Biomedical Sciences, Curtin University, Bentley, Australia.


OBJECTIVE: HIV-associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving anti-retroviral therapy (ART), even though neurotoxic anti-retroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesise that chemokines produced locally in the skin promote migration of macrophages and T-cells into the tissue, damaging cutaneous nerves causing HIV-SN. DESIGN: We assessed chemokine receptor expression on infiltrating CD14 and CD3 cells around cutaneous nerves in standardised skin biopsies from HIV-SN+ patients (n = 5), HIV-SN- patients (n = 9) and healthy controls (n = 4). METHODS: The AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen was used to assess Indonesian HIV+ patients receiving ART without stavudine (case definition: bilateral presence of at least one symptom and at least one sign of neuropathy). Distal leg skin biopsies were stained to visualise chemokine receptors; CCR2, CCR5, CXCR3, CXCR4, CX3CR1, infiltrating CD3 and CD14 cells and protein-gene-product 9.5 on nerves, using immunohistochemistry and 4-colour confocal microscopy. RESULTS: Intraepidermal nerve fibre density was variable in patients without HIV-SN and generally lower in those with HIV-SN. CX3CR1 was more evident on CD14 cells whereas CCR2, CCR5, CXCR3 and CXCR4 were more common on CD3 cells. Expression of CX3CR1, CCR2 and CCR5 was more common in HIV-SN+ patients than those without HIV-SN. CXCR3 and CXCR4 were upregulated in all HIV+ patients, compared with healthy controls. CONCLUSION: Inflammatory macrophages expressing CX3CR1 and T-cells expressing CCR2 and CCR5 may participate in peripheral nerve damage leading to HIV-SN in HIV+ patients treated without stavudine. Further characterisation of these cells is warranted.


  • Journal: AIDS
  • Published: 01/02/2018
  • Volume: 32
  • Issue: 4
  • Pagination: 431-441