Gilad Halpert1, Abdulla Watad2, Avishai M Tsur3, Arad Dotan4, Hector Enrique Quiros-Lim5, Harald Heidecke6, Boris Gilburd7, Josef Haik8, Yair Levy9, Miri Blank7, Howard Amital2, Yehuda Shoenfeld7. 1. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat- Gan, 52621, Israel; Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. Electronic address: Gilad.Halpert@sheba.health.gov.il. 2. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat- Gan, 52621, Israel; Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine 'B' and Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Israel. 3. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat- Gan, 52621, Israel; Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan, Israel; Department of Military Medicine, Hebrew University of Jerusalem Faculty of Medicine, Jerusalem, Israel. 4. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat- Gan, 52621, Israel. 5. Department of Plastic and Reconstructive Surgery. The Chaim Sheba Medical Center at Tel Hashomer. Ramat Gan. Israel. 6. CellTrend GmbH, Luckenwalde, Germany. 7. Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer, Ramat- Gan, 52621, Israel; Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel. 8. Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Plastic and Reconstructive Surgery. The Chaim Sheba Medical Center at Tel Hashomer. Ramat Gan. Israel; College of Health and Medicine. University of Tasmania, Sydney, NSW, Australia; Institute for Health Research. University of Notre Dame, Fremantle, Australia. 9. Affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Medicine E, Meir Medical Center, Kfar Saba, Israel.
Abstract
IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method. These women with SBIs addressed our clinic due to various subjective and autonomic-related manifestations such as chronic severe fatigue, cognitive impairment, widespread pain, memory loss, sleep disorders, palpitations, depression, hearing abnormalities etc. We report for the first time, a significant reduction in the sera level of anti-β1 adrenergic receptor (p < 0.001), anti-angiotensin II type 1 receptor (p < 0.001) and anti-endothelin receptor type A (p = 0.001) autoantibodies in women with SBIs (n = 93) as compared with aged matched healthy women (n = 36). Importantly, anti-β1 adrenergic receptor autoantibody was found to significantly correlate with autonomic-related manifestations such as: sleep disorders and depression in women with SBIs. CONCLUSIONS: Chronic immune stimulation by silicone material may lead to an autoimmune dysautonomia in a subgroup of potentially genetically susceptible women with SBIs. The appearance of autoantibodies against GPCRs of the autonomic nervous system serve as an explanation for the subjective autonomic-related manifestations reported in women with SBIs.
IMPORTANCE AND OBJECTIVES: There is unmet medical need to understand the pathogenic mechanism of the panoply of clinical manifestations associated with silicone breast implants (SBIs) such as severe fatigue, widespread pain, palpitations, dry mouth and eyes, depression, hearing loss etc. We aimed to determine whether autoantibodies against the autonomic nervous system receptors can explain the enigmatic and subjective clinical manifestation reported by women with SBIs. RESULTS: Circulating level of autoantibodies against G protein-coupled receptors (GPCRs) of the autonomic nervous system (adrenergic, muscarinic, endothelin and angiotensin receptors) have been evaluated in symptomatic women with SBIs using an ELISA method. These women with SBIs addressed our clinic due to various subjective and autonomic-related manifestations such as chronic severe fatigue, cognitive impairment, widespread pain, memory loss, sleep disorders, palpitations, depression, hearing abnormalities etc. We report for the first time, a significant reduction in the sera level of anti-β1 adrenergic receptor (p < 0.001), anti-angiotensin II type 1 receptor (p < 0.001) and anti-endothelin receptor type A (p = 0.001) autoantibodies in women with SBIs (n = 93) as compared with aged matched healthy women (n = 36). Importantly, anti-β1 adrenergic receptor autoantibody was found to significantly correlate with autonomic-related manifestations such as: sleep disorders and depression in women with SBIs. CONCLUSIONS: Chronic immune stimulation by silicone material may lead to an autoimmune dysautonomia in a subgroup of potentially genetically susceptible women with SBIs. The appearance of autoantibodies against GPCRs of the autonomic nervous system serve as an explanation for the subjective autonomic-related manifestations reported in women with SBIs.