Anti-cytokine autoantibodies in postherpetic neuralgia. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Bayat, Ahmad; Burbelo, Peter; Browne, Sarah; Quinlivan, Mark; Martinez, Bianca; Holland, Steven; Buvanendran, Asokumar; Kroin, Jeffrey; Mannes, Andrew; Breuer, Judith; Cohen, Jeffrey; Iadarola, Michael
• Is Part Of: Journal of translational medicine. Volume 13:Issue 1(2015)
• Page Start: 1
• Page End: 8
• Publication Date: 2015-12
• Subjects: Anti-cytokine autoantibodies -- Herpes zoster (HZ) -- Opportunistic infection -- Pain -- PHN -- Shingles -- Varicella zoster virus (VZV); Medicine, Experimental -- Periodicals; Human experimentation in medicine -- Periodicals; Therapeutics -- Periodicals; 615.50724
• DOI: 10.1186/s12967-015-0695-6
• Languages: English
• ISSNs: 1479-5876

Abstract

Abstract 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.