Ann Arthritis Clin Rheumatol | Volume 2, Issue 2 | Research Article | Open Access

Autoantibodies against Autonomic Nerve Receptors in Adolescent Japanese Girls after Immunization with Human Papillomavirus Vaccine

Akiyo Hineno1,2, Shu-ichi Ikeda1*, Carmen Scheibenbogen3,4, Harald Heidecke5, Kai Schulze- Forster5, Juliane Junker5, Gabriela Riemekasten6, Ralf Dechend8, Duska Dragun9 and Yehuda Shoenfeld10

1Intractable Disease Care Center, Shinshu University Hospital, Japan
2Department of Medicine (Neurology and Rheumatology), Shinshu University School of Medicine, Japan
3Department of Medicine, Institute for Medical Immunology, Germany
4Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Germany
5Cell Trend GmbH, Germany
6Department of Rheumatology, Universitätsklinikum Schleswig-Holstein, Germany
7Experimental and Clinical Research Center, Charité-Universitätsmedizin Berlin Germany
8Department of Cardiology and Nephrology, HELIOS-Klinikum, Germany
9Department of Nephrology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Germany
10Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel

*Correspondance to: Shu-ichi Ikeda 

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In Japan a significant number of adolescent girls complain of unusual symptoms after human papillomavirus (HPV) vaccination, and these symptoms, composed of orthostatic dysregulation, chronic regional pain syndrome (CRPS) and cognitive dysfunction are considered adverse effects of HPV vaccination. However, a causal link between HPV vaccination and these adverse effects has not been demonstrated. In the present study, we investigated autoantibodies against diverse Gprotein coupled receptors in the serum of girls who complained of possible adverse effects after HPV vaccination. Fifty five girls with HPV vaccination and 57 girls without HPV immunization were enrolled in the study. The serum levels of autoantibodies against the adrenergic receptors α1, α2, β1and β2, muscarinic acetylcholine receptors 1, 2, 3, 4, 5; and endothelin receptor A was significantly elevated in girls with HPV vaccination, compared with those in the controls. The serum levels of these autoantibodies tended to decrease with the time course of the illness, but there was no statistically meaningful association between the clinical symptoms and elevated serum levels of these autoantibodies. This preliminary study provides evidence that post-vaccination abnormal autoimmunity plays an important role in the development of unique symptoms after HPV vaccination.


Autonomic nerve dysfunction; Autoantibody; Autoimmune disorder; Chronic regional pain syndrome; HPV; Human papilloma vaccination; Chronic regional pain syndrome


Hineno A, Shu-ichi Ikeda, Scheibenbogen C, Heidecke H, Schulze- Forster K, Junker, et al. Autoantibodies against Autonomic Nerve Receptors in Adolescent Japanese Girls after Immunization with Human Papillomavirus Vaccine. Ann Arthritis Clin Rheumatol. 2019; 2(2): 1014.

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