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Expression of CCR-5/CXCR-4 in spinal cord of patients with AIDS
S F An1, O Osuntokun, M Groves
1Department of Neuropathology, Institute of Neurology, University College London, UK. S.An@ion.ucl.ac.uk
Abstract:
The discovery that chemokines and their receptors (in particular CXCR-4 and CCR-5) play a role in HIV infection challenges traditional views on the pathogenesis of HIV infection in man and identifies new potential targets for therapeutic intervention. Several groups as well as our pilot study have found that increased numbers of CCR-5 positive macrophage/microglia correlate with disease severity in brains of patients with AIDS. Among HIV-related disorders, vacuolar myelopathy (VM) is the most common spinal cord disorder in patients with AIDS. The purpose of this study was to investigate the possible relationship between the expression of CCR-5/CXCR-4 and spinal cord pathology in patients with AIDS. Thirty-four spinal cords (forming two groups: without and with VM) of patients with AIDS and 6 HIV-1-negative controls were investigated by routine histological examination and immunohistochemistry. Elevated expression of CXCR-4 was found in most AIDS cases with/without neuropathological disorders (8/17 and 13/16, respectively). No CCR-5 expression was detected in HIV-1-negative controls. Among 34 cases with AIDS, expression of CCR-5 was detected in 1/16 HIV-1-positive normal spinal cords and 5/18 with VM. Despite the lack of statistical significance between the two groups (P=0.1019), our results suggest that CCR-5/CXCR-4 are present in spinal cord of patients with AIDS and that CCR-5 is more frequently found in association with VM.
Insights
Chemokine receptors CXCR-4 and CCR-5 are present in the spinal cords of patients with AIDS. CCR-5 expression showed a potential association with vacuolar myelopathy (VM), a common spinal cord disorder in AIDS patients.
Area of Science:
- Neuroscience
- Immunology
- Virology
Background:
- Chemokines and their receptors, notably CXCR-4 and CCR-5, are implicated in HIV pathogenesis.
- Increased CCR-5 positive macrophage/microglia correlate with disease severity in the brain of AIDS patients.
- Vacuolar myelopathy (VM) is a prevalent spinal cord disorder in individuals with AIDS.
Purpose of the Study:
- To investigate the relationship between CCR-5/CXCR-4 expression and spinal cord pathology in AIDS patients.
- To determine if CCR-5/CXCR-4 expression differs in spinal cords with and without VM.
Main Methods:
- Histological examination and immunohistochemistry were performed on 34 spinal cords from AIDS patients (with and without VM) and 6 HIV-1-negative controls.
- Analysis focused on the expression of chemokine receptors CCR-5 and CXCR-4.
Main Results:
- Elevated CXCR-4 expression was observed in most AIDS cases, irrespective of neuropathological disorders.
- CCR-5 expression was not detected in HIV-1-negative controls.
- CCR-5 was detected in one normal spinal cord and five spinal cords with VM among AIDS patients, suggesting a potential association with VM (P=0.1019).
Conclusions:
- CXCR-4 and CCR-5 are present in the spinal cords of patients with AIDS.
- CCR-5 expression may be more frequently associated with vacuolar myelopathy in AIDS patients.
- These findings highlight potential therapeutic targets for HIV-related spinal cord pathologies.