Overall, our findings do not support a major role for silicone implants in inducing monoclonal gammopathies in humans and are consistent with conclusions of prior investigations of silicone implants and MGUS [13,14] or MM [29-31]. We observed higher prevalence of paraproteinemia in Arformoterol tartrate women with CTD both with and without silicone implants (8.0% and 4.5%, respectively) than those reported PIK3CB for similarly aged women with any type of breast implants (1.4C1.7%) in one study [14]. -globulin, -globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51C6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent populace of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation. Introduction Local adverse effects from silicone implants, which include surgically placed devices as well as injections of liquid silicone, are well recognized [1,2], but systemic effects are not supported by current studies. Systematic reviews [3,4] and four meta-analyses including data from up to 20 retrospective cohort, caseCcontrol, and cross-sectional studies [5-8] have failed to find significantly increased risks of any CTD after receiving silicone implants. Few studies, however, have evaluated serum proteins and paraproteins in women with silicone implants. Plasmacytomas have been induced with silicone gel from breast implants in susceptible mouse strains [9], and several uncontrolled clinical reports suggested that silicone implants might be associated with multiple myeloma (MM) and its possible precursor, monoclonal gammopathy of undetermined significance (MGUS) [10-12]. One investigation evaluated the risk for MGUS in a retrospective caseCcontrol study of women with and without silicone implants, and found a nonsignificant increase (odds ratio, 1.25; 95% confidence interval, 0.27C6.39) [13]. Another caseCcontrol study found no increase in immunoglobulin levels or other immunologic parameters, with the exception of anti-single-stranded DNA autoantibodies, in women with silicone implants [14]. None of these studies, however, assessed the role of concomitant CTD, which has been reported to be a risk factor for monoclonal immunoglobulins (paraproteins) and is associated with MGUS in 3C6% of cases [15]. The possible increased risk of paraproteins in women with silicone implants and CTD, as well as the limited information on other serum proteins in this populace, prompted us to assess whether silicone implants in women who subsequently developed CTD are associated with altered serum protein profiles and/or a higher prevalence of serum paraproteins. Materials and methods Patients and study design All patients were enrolled prospectively in studies of the pathogenesis of the diseases described, and extensive clinical information was collected at enrollment to ensure subjects met the diagnostic criteria. The current study was retrospective in that subjects enrolled in the prior studies were identified based on the presence of a stored serum sample. The primary study populace (Group 1) Arformoterol tartrate included 74 women who designed CTD after receiving silicone implants. Group 1 were enrolled in studies of the pathogenesis of CTD developing after receiving silicone implants at the US Food and Drug Administration (FDA) and the National Institutes of Health (NIH) from 1993 to 2000. These subjects were matched to 74 age-matched and CTD-matched women without silicone implants (Group 2) enrolled in other protocols at the FDA and NIH between 1993 and 2000, and subjects from a study of the underlying mechanisms of major fibromyalgia (fibromyalgia symptoms (FMS)) from 1986 to 1989 and from the first Undifferentiated Connective Cells Disease research within the Cooperative Organized Studies from the Rheumatic Illnesses enrolled between 1982 and 1987. We also matched up 14 ladies with silicon implants but no CTD (Group 3) to 14 ladies without silicon implants or CTD (Group 4) for exploratory assessments of the consequences of silicon implants without CTD. In additional exploratory analyses, instances from Group 2 which were discovered to possess paraproteins were weighed against those paraprotein instances Arformoterol tartrate in independent sets of 28 ladies with CTD but without silicon implants (Group 5), and had been weighed against 10 ladies with.