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.
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.
J Autoimmun. 2021 Jun;120:102631. doi: 10.1016/j.jaut.2021.102631. Epub 2021 Mar 31.
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.
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.
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.
了解与硅胶乳房植入物(SBIs)相关的各种临床表现(如严重疲劳、广泛疼痛、心悸、口干眼干、抑郁、听力损失等)的致病机制存在未满足的医学需求。我们旨在确定针对自主神经系统受体的自身抗体是否可以解释 SBIs 女性报告的神秘和主观的临床症状。
使用 ELISA 方法评估了有症状的 SBIs 女性中自主神经系统(肾上腺素能、毒蕈碱能、内皮素和血管紧张素受体)G 蛋白偶联受体(GPCR)的循环自身抗体水平。这些 SBIs 女性因各种主观和自主相关的表现而到我们的诊所就诊,如慢性严重疲劳、认知障碍、广泛疼痛、记忆力减退、睡眠障碍、心悸、抑郁、听力异常等。我们首次报告,SBIs 女性(n=93)的血清中抗β1 肾上腺素能受体(p<0.001)、抗血管紧张素 II 型 1 受体(p<0.001)和抗内皮素受体 A(p=0.001)自身抗体水平显著降低与年龄匹配的健康女性(n=36)相比。重要的是,抗β1 肾上腺素能受体自身抗体与 SBIs 女性的自主相关表现(如睡眠障碍和抑郁)显著相关。
硅胶材料的慢性免疫刺激可能导致 SBIs 中潜在遗传易感女性亚群发生自身免疫性自主神经功能障碍。针对自主神经系统 GPCR 的自身抗体的出现为 SBIs 女性报告的主观自主相关表现提供了一种解释。