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2015 ; 13
(ä): 333
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Anti-cytokine autoantibodies in postherpetic neuralgia
#MMPMID26482341
Bayat A
; Burbelo PD
; Browne SK
; Quinlivan M
; Martinez B
; Holland SM
; Buvanendran A
; Kroin JS
; Mannes AJ
; Breuer J
; Cohen JI
; Iadarola MJ
J Transl Med
2015[Oct]; 13
(ä): 333
PMID26482341
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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-?, interferon-?, 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-?, 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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