Some patients who develop painful postherpetic neuralgia (PHN) following varicella zoster virus (VZV)reactivation may have several sporadic anti-cytokine autoantibodies present, creating a deficit in immunesignaling.

The immunodeficiency syndrome in these patients may increase susceptibility to PHN, according to findings by Ahmad Bayat, MD, of the National Institutes of Health, and colleagues.

The study, published in the Journal of Translational Medicine, documents the presence of autoantibodies againstseveral cytokines and other autoantigens in patients with herpes zoster (HZ) who have or don’t have PHN.

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Dr Bayat and colleagues collected sera samples from 115 HZ patients with PHN and 83 without PHN. A cohort ofpatients with complex regional pain syndrome or neuropathic pain was also tested against the selected cytokinesas controls. Antibody levels against VZV, Epstein Barr virus, and herpes simplex virus-2 were also tested inpatients with HZ and PHN.

Six patients with PHN showed markedly elevated levels of single, autoantibodies against interferon-α, interferon-γ, GM-CSF, or interleukin-6, while those with HZ without PHN and the pain control group showed low or noautoantibodies against the four cytokines. One PHN patient with high levels of anti-interleukin-6 autoantibodieshad a significantly depressed antibody level to VZV, which possibly reflects poor T-cell immunity against VZV.Further, in vitro functional testing showed that 3 of the 5 PHN patients who tested positive for anti-cytokineautoantibody had neutralizing autoantibodies against interferon-α, GM-CSF, or interleukin-6, compared to none ofthe HZ patients without PHN. This finding suggests that anti-cytokine immunodeficiency may contribute todevelopment of PHN.

“It is likely that the development of PHN is a highly complex, multifactorial process driven by many subtlegenetic, environmental, and acquired factors,” the authors wrote. “Since autoantibodies and decline in immunesystem function are known to occur more commonly in older subjects the present observations suggestthe likelihood that there may be additional, unrecognized pathogenic autoantibodies against other immunecomponents in older subjects that may increase susceptibility to PHN.”


1. Bayat A, Burbelo PD, Browne SK, et al. Anti-cytokine autoantibodies in postherpetic neuralgia. J Transl Med. 2015; doi:10.1186/s12967-015-0695-6.

This article originally appeared on Neurology Advisor