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

Jenjira Mountford, Fitri Octaviana, Riwanti Estiasari, Denise Dewanto Setiawan, Ibnu Ariyanto, Silvia Lee, Jessica Gaff, Constance Chew, Connie Jackaman, Peter Kamerman, Catherine Cherry, Patricia Price

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Objective: HIV-Associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving antiretroviral therapy (ART), even though neurotoxic antiretroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesize 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 standardized 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 visualize 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 characterization of these cells is warranted.

Original languageEnglish
Pages (from-to)431-441
Number of pages11
JournalAIDS
Volume32
Issue number4
DOIs
Publication statusPublished - 20 Feb 2018

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Chemokine Receptors
HIV
Skin
Stavudine
Macrophages
T-Lymphocytes
Biopsy
Peripheral Nervous System Diseases
Peripheral Nerves
Nerve Fibers
Chemokines
Confocal Microscopy
Leg
Acquired Immunodeficiency Syndrome
Color
Immunohistochemistry

Cite this

Mountford, Jenjira ; Octaviana, Fitri ; Estiasari, Riwanti ; Setiawan, Denise Dewanto ; Ariyanto, Ibnu ; Lee, Silvia ; Gaff, Jessica ; Chew, Constance ; Jackaman, Connie ; Kamerman, Peter ; Cherry, Catherine ; Price, Patricia. / Ex-vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-Associated sensory neuropathy. In: AIDS. 2018 ; Vol. 32, No. 4. pp. 431-441.
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title = "Ex-vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-Associated sensory neuropathy",
abstract = "Objective: HIV-Associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving antiretroviral therapy (ART), even though neurotoxic antiretroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesize 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 standardized 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 visualize 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 characterization of these cells is warranted.",
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author = "Jenjira Mountford and Fitri Octaviana and Riwanti Estiasari and Setiawan, {Denise Dewanto} and Ibnu Ariyanto and Silvia Lee and Jessica Gaff and Constance Chew and Connie Jackaman and Peter Kamerman and Catherine Cherry and Patricia Price",
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Mountford, J, Octaviana, F, Estiasari, R, Setiawan, DD, Ariyanto, I, Lee, S, Gaff, J, Chew, C, Jackaman, C, Kamerman, P, Cherry, C & Price, P 2018, 'Ex-vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-Associated sensory neuropathy' AIDS, vol. 32, no. 4, pp. 431-441. https://doi.org/10.1097/QAD.0000000000001714

Ex-vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-Associated sensory neuropathy. / Mountford, Jenjira; Octaviana, Fitri; Estiasari, Riwanti; Setiawan, Denise Dewanto; Ariyanto, Ibnu; Lee, Silvia; Gaff, Jessica; Chew, Constance; Jackaman, Connie; Kamerman, Peter; Cherry, Catherine; Price, Patricia.

In: AIDS, Vol. 32, No. 4, 20.02.2018, p. 431-441.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Ex-vivo expression of chemokine receptors on cells surrounding cutaneous nerves in patients with HIV-Associated sensory neuropathy

AU - Mountford, Jenjira

AU - Octaviana, Fitri

AU - Estiasari, Riwanti

AU - Setiawan, Denise Dewanto

AU - Ariyanto, Ibnu

AU - Lee, Silvia

AU - Gaff, Jessica

AU - Chew, Constance

AU - Jackaman, Connie

AU - Kamerman, Peter

AU - Cherry, Catherine

AU - Price, Patricia

PY - 2018/2/20

Y1 - 2018/2/20

N2 - Objective: HIV-Associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving antiretroviral therapy (ART), even though neurotoxic antiretroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesize 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 standardized 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 visualize 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 characterization of these cells is warranted.

AB - Objective: HIV-Associated sensory neuropathy (HIV-SN) remains common in HIV+ individuals receiving antiretroviral therapy (ART), even though neurotoxic antiretroviral drugs (e.g. stavudine) have been phased out of use. Accumulating evidence indicates that the neuropathy is immune-mediated. We hypothesize 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 standardized 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 visualize 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 characterization of these cells is warranted.

KW - CD14 + cells

KW - CD3 + cells

KW - chemokine receptors

KW - HIV-sensory neuropathy

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U2 - 10.1097/QAD.0000000000001714

DO - 10.1097/QAD.0000000000001714

M3 - Article

VL - 32

SP - 431

EP - 441

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 4

ER -