Abstract Body

A clear association between the clinical picture of symptomatic women with silicone breast implants and dysregulated immunity was in dispute for decades. Recently, our group found, in a large-population based study, that women with silicone breast implant (SBI) have a significant increased risk to develop autoimmune diseases. Moreover, we reported a significant change in the titters of circulating IgG autoantibodies directed against G-protein coupled receptors (GPCRs) of the autonomic nervous system in symptomatic women with SBI, which might explain some of their subjective and autonomic-related manifestations. So far, the potential pathogenic functional effects of autoantibodies derived from symptomatic women with SBI have not been explored. In the current study, we describe for the first time, the in vitro and in-vivo functional activity of purified IgG antibodies derived from symptomatic women with SBI. Our in vitro studies shows that while healthy-derived IgG reduces the secretion of pro-inflammatory cytokines (TNFα and IL-6) by human monocytes in response to bacterial lipopolysaccharide (LPS), IgG derived from SBI women increases the production of these cytokines. Importantly, we directly injected IgGs derived from symptomatic women with SBI (suffering from autonomic-related manifestations such as cognitive impairment and depression) into mice brains. Behavioral studies demonstrated a specific and transient significant increment (about 60%) in the time spent at the center of the open field arena as compared with mice injected with IgG from healthy women (without SBI), apparently indicating anxiolytic outcome of SBI-IgG. This effect was accompanied with a strong trend of reduction of the locomotor activity of the SBI-IgG treated mice, indicating an apathic behavior masked by an anxiolytic-like behavior. Our study is the first to show the pathogenic functional activity of IgG autoantibodies in symptomatic women with SBI, emphasizing the importance of these antibodies as potential targets for antibody-depleting therapies in silicone breast implant related illness.