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Anti-cytokine autoantibodies in postherpetic neuralgia

BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportuni...

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Autores principales: Bayat, Ahmad, Burbelo, Peter D., Browne, Sarah K., Quinlivan, Mark, Martinez, Bianca, Holland, Steven M., Buvanendran, Asokumar, Kroin, Jeffrey S., Mannes, Andrew J., Breuer, Judith, Cohen, Jeffrey I., Iadarola, Michael J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617715/
https://www.ncbi.nlm.nih.gov/pubmed/26482341
http://dx.doi.org/10.1186/s12967-015-0695-6
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author Bayat, Ahmad
Burbelo, Peter D.
Browne, Sarah K.
Quinlivan, Mark
Martinez, Bianca
Holland, Steven M.
Buvanendran, Asokumar
Kroin, Jeffrey S.
Mannes, Andrew J.
Breuer, Judith
Cohen, Jeffrey I.
Iadarola, Michael J.
author_facet Bayat, Ahmad
Burbelo, Peter D.
Browne, Sarah K.
Quinlivan, Mark
Martinez, Bianca
Holland, Steven M.
Buvanendran, Asokumar
Kroin, Jeffrey S.
Mannes, Andrew J.
Breuer, Judith
Cohen, Jeffrey I.
Iadarola, Michael J.
author_sort Bayat, Ahmad
collection PubMed
description BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN.
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spelling pubmed-46177152015-10-25 Anti-cytokine autoantibodies in postherpetic neuralgia Bayat, Ahmad Burbelo, Peter D. Browne, Sarah K. Quinlivan, Mark Martinez, Bianca Holland, Steven M. Buvanendran, Asokumar Kroin, Jeffrey S. Mannes, Andrew J. Breuer, Judith Cohen, Jeffrey I. Iadarola, Michael J. J Transl Med Research BACKGROUND: The mechanisms by which varicella zoster virus (VZV) reactivation causes postherpetic neuralgia (PHN), a debilitating chronic pain condition, have not been fully elucidated. Based on previous studies identifying a causative role for anti-cytokine autoantibodies in patients with opportunistic infections, we explored this possibility in PHN. METHODS: Sera from herpes zoster (HZ) patients without and with PHN (N = 115 and 83, respectively) were examined for the presence of autoantibodies against multiple cytokines, and other known autoantigens. In addition, a cohort of patients with complex regional pain syndrome or neuropathic pain was tested for autoantibodies against selected cytokines. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also measured in the HZ and PHN patients. Patient sera with high levels of anti-cytokine autoantibodies were functionally tested for in vitro neutralizing activity. RESULTS: Six PHN subjects demonstrated markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6. In contrast, the HZ and the pain control group showed low or no autoantibodies, respectively, against these four cytokines. Further analysis revealed that one PHN patient with high levels of anti-interleukin-6 autoantibodies had a markedly depressed antibody level to VZV, potentially reflecting poor T cell immunity against VZV. In vitro functional testing revealed that three of the five anti-cytokine autoantibody positive PHN subjects had neutralizing autoantibodies against interferon-α, GM-CSF or interleukin-6. In contrast, none of the HZ patients without PHN had neutralizing autoantibodies. CONCLUSIONS: These results suggest the possibility that sporadic anti-cytokine autoantibodies in some subjects may cause an autoimmune immunodeficiency syndrome leading to uncontrolled VZV reactivation, nerve damage and subsequent PHN. BioMed Central 2015-10-20 /pmc/articles/PMC4617715/ /pubmed/26482341 http://dx.doi.org/10.1186/s12967-015-0695-6 Text en © Bayat et al. 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Bayat, Ahmad
Burbelo, Peter D.
Browne, Sarah K.
Quinlivan, Mark
Martinez, Bianca
Holland, Steven M.
Buvanendran, Asokumar
Kroin, Jeffrey S.
Mannes, Andrew J.
Breuer, Judith
Cohen, Jeffrey I.
Iadarola, Michael J.
Anti-cytokine autoantibodies in postherpetic neuralgia
title Anti-cytokine autoantibodies in postherpetic neuralgia
title_full Anti-cytokine autoantibodies in postherpetic neuralgia
title_fullStr Anti-cytokine autoantibodies in postherpetic neuralgia
title_full_unstemmed Anti-cytokine autoantibodies in postherpetic neuralgia
title_short Anti-cytokine autoantibodies in postherpetic neuralgia
title_sort anti-cytokine autoantibodies in postherpetic neuralgia
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4617715/
https://www.ncbi.nlm.nih.gov/pubmed/26482341
http://dx.doi.org/10.1186/s12967-015-0695-6
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