Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination

Yukitoshi Takahashi; Takashi Matsudaira; Hitoshi Nakano; Hirosato Nasu; Hitoshi Ikeda; Kentaro Nakaoka; Rumiko Takayama; Masayasu Oota

doi:10.1016/j.jneuroim.2016.07.003

Immunological studies of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination

J Neuroimmunol. 2016 Sep 15:298:71-8. doi: 10.1016/j.jneuroim.2016.07.003. Epub 2016 Jul 7.

Authors

Yukitoshi Takahashi¹, Takashi Matsudaira², Hitoshi Nakano³, Hirosato Nasu⁴, Hitoshi Ikeda⁵, Kentaro Nakaoka⁶, Rumiko Takayama⁷, Masayasu Oota⁸

Affiliations

¹ National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan; Department of Pediatrics, Gifu University School of Medicine, Yanagido, Gifu, Japan. Electronic address: takahashi-ped@umin.ac.jp.
² National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan. Electronic address: taka-m56@shizuokamind.org.
³ National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan. Electronic address: hinakano@shizuokamind.org.
⁴ National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan. Electronic address: evo10bibi@gmail.com.
⁵ National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan. Electronic address: h-ikeda@shizuokamind.org.
⁶ National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, NHO, 886 Urushiyama, Aoi-ward, Shizuoka, Japan. Electronic address: k-naka@shizuokamind.org.
⁷ Department of Pediatrics, Hokkaido Medical Center for Child Health and Rehabilitation, 1-1-240 Kanayama, Teine-ward, Sapporo, Japan. Electronic address: takayama921@gmail.com.
⁸ Department of Pediatrics, JA Toride Medical Center, 2-1-1, Hongo, Toride, Japan. Electronic address: fuemiyasu@k7.dion.ne.jp.

PMID: 27609278
DOI: 10.1016/j.jneuroim.2016.07.003

Abstract

In 32 patients with prolonged central nervous system symptoms after human papillomavirus (HPV) vaccination, we measured conventional and immunological markers in cerebrospinal fluid (CSF) and compared with the levels in disease controls. Our studies revealed significantly decreased chloride and neuron-specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells increased significantly in patients, and IL-17 increased significantly from 12 to 24months after symptom onset. Chemokines (IL-8 and MCP-1) were also elevated, but CD8(+) T cells, PDGF-bb and IL-12 were reduced. Antibodies to GluN2B-NT2, GluN2B-CT and GluN1-NT increased significantly. These results suggest biological, mainly immunological, changes in the CSF of patients after HPV vaccination.

Keywords: Autonomic disorder; Cognitive disorder; Human papillomavirus vaccine; Motor disorder; Sensory disorder.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Autoantibodies / cerebrospinal fluid
CD4-Positive T-Lymphocytes / pathology
Central Nervous System Diseases / cerebrospinal fluid*
Central Nervous System Diseases / etiology*
Central Nervous System Diseases / immunology
Central Nervous System Diseases / pathology
Child
Cytokines / cerebrospinal fluid*
Female
Granzymes / cerebrospinal fluid
Humans
Intercellular Signaling Peptides and Proteins / cerebrospinal fluid
Papillomavirus Vaccines / adverse effects*
Phosphopyruvate Hydratase / cerebrospinal fluid
Receptors, N-Methyl-D-Aspartate / immunology
Statistics, Nonparametric
Vaccination / adverse effects*
Young Adult

Substances

Autoantibodies
Cytokines
Intercellular Signaling Peptides and Proteins
NR2B NMDA receptor
Papillomavirus Vaccines
Receptors, N-Methyl-D-Aspartate
Granzymes
Phosphopyruvate Hydratase