Anti-cytokine autoantibodies in postherpetic neuralgia

作者：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

来源：Journal of Translational Medicine, 2015, 13(1): 333.

DOI：10.1186/s12967-015-0695-6

• Anti-cytokine autoantibodies
• Herpes zoster (HZ)
• Opportunistic infection
• Pain
• PHN
• Shingles
• Varicella zoster virus (VZV)

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-a, interferon-gamma, 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-a, 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.

• 出版日期2015-10-20