Objective: To investigate the clinical manifestations of neuropsychiatric side effects after the Human papillomavirus (HPV) vaccine, and to investigate the immunological actions and epigenetic modification.

Background: Human papillomavirus (HPV) typically causes chronic infections, which can be isolated from skin swabs and hair from normal immunocompetent individuals. HPV- associated cancer, such as cervical cancer, can result from persistent infection with the high risk type of HPV 16 and 18, with the characteristic immuonological escape from cell-mediated immunity of the host. Prophylactic vaccine of HPV for cervical cancer was discovered with recombinant gene technology in 1990, and it was adopted in preventive vaccination law in 2013 in Japan. Vaccine adjuvanthas been incorporated, which strongly induces the CD8+ T cell-dominate Th2 responses.

Methods: The cohort comprised 7 patients (mean age; 17.4±１years) and their 3 sisters who had not been received HPVs vaccinations as controls, we followed them from 2013 to 2018 for 6 years. Immunological and epigenetic biomarkers with their blood and CSF samples were evaluated. Molecular analysis were conducted with illumine multiplexed sequencing.

Results: Their clinical manifestations were variable: chronic headache, 5/7 (71%); depressive state, 4/7 (57%); cognitive impairment, 3/7 (43%); myoclonic epilepsy, 2/7 (29%); functional conversion reaction, 1/7 (14%); motor sensory neuritis, 3/7 (57%); neuralgic pain, 1/7 (14%). Their immunological and epigenetic biomarkers were as followed: atopic predisposition with serum IgE elevation, 5/7 (71%); IL-6/IL-17 elevation, 1/7 (71%); positive for anti NMDA-type Glutamine receptor antibody, 4/7 (57%); positive for anti GM1-IgM antibody, 2/7 (33%). decreased DNA methylations on IL-17 cording gene(Chr6p12) and IL-17 receptor cording gene (Chr22 q11), 5/7 (71%). After six years of follow-up, 5/7 (71%) patients were improved slightly but 2/7 (33%) patients had severe sequelaes.

Conclusions: We suggest that the shift to Th2 responses under the condition of immature epigenetic gene regulation may be triggered by HPV vaccination, which may introduce the diverse anti-neural antibodies, then disturb the central and peripheral nervous system insidiously.

References: 1) Y Takahashi, et al. Immunological studied of cerebrospinal fluid from patients with CNS symptoms after human papillomavirus vaccination. J of Neuroimmunology 2016, 298, 71-78.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/molecular-immunological-action-and-epigenetic-modification-of-the-human-papillomavirus-vaccination-and-associated-neuropsychiatric-side-effects/