Silicone implant controversy.
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Breast Implants↗
Biomedical subjects
S S Teuber
Publications and source records attributed to S S Teuber.
Multiple autoantibodies in patients with silicone breast implants.
Diverse immunologic abnormalities have been described in women who received silicone breast implants. However, most studies have focused on either a limited number of patients or a small panel of autoantibodies. We report the analysis of 20 autoantibodies in 116 women with implants and 134 controls. The patients ranged from 26- to 66-years-old, with a mean of 45.7 +/- 8.3 years; breast prostheses were in place for a mean of 15 +/- 5.6 years, with a range of 4 to 30, the chief complaints of the 116 patients included polyarthralgias, fatigue, myalgias, morning stiffness, and decreased memory. All 250 sera were tested blindly using a panel of 20 autoantigens including SS-A, SS-B, RNP, cardiolipin (CL), collagen types I, II and IV, phosphatidylserine (PS), myeloperoxidase (MPO), sulfatides (sulf), thyroglobulin (TG), gangliosides (GDIa;GM2), proteinase-3 (PR3), Jo-1, Sm, HPRPP-ribosomal phosphate, histones (H2AH2B), Scl-70 and glomerular basement membrane (NC-1). Values from individual patients were considered positive only when greater than 3 SD above the control mean. There was a statistically significant greater frequency of autoantibodies in women with implants for 15 of the 20 autoantigens; these were particularly striking for anti-H2AH2B, HPRPP, SS-A, SS-B, Scl-70, CL, PS, GM2, and NC-1. Many patients harbored several autoantibodies; 20% had four autoantibodies; 8% had six autoantibodies. The association of autoantibodies and implants suggests an adjuvant action of silicon/silicone byproducts.
Adjuvants, Immunologic↗
Elevated serum silicon levels in women with silicone gel breast implants.
The metabolic fate of silicone gel leaked from an intact or ruptured prosthesis is unknown. In this study, serum was blindly assayed by inductively coupled plasma atomic emission spectroscopy (ICP-AES) for elemental silicon in 72 women with silicone gel breast implants and 55 control women (mean age 48 yr, both groups). Blood was drawn and processed using silicon-free materials. The mean silicon level in controls was 0.13 +/- 0.07 mg/L (range 0.06-0.35 mg/L), whereas in implant patients, the mean was significantly higher at 0.28 +/- 0.22 mg/L (range 0.06-0.87 mg/L) (P < 0.01, Student's t-test with correction for unequal variances). Using the mean of the control group + 2 SD as a cutoff for normal range (0.27 mg/L), 25/72 (34.7%) implant patients exceeded this value, compared with 2/55 (3.6%) controls. There was no significant correlation between past rupture of one or both implants, current rupture at the time of the blood draw, or the number of years with implants and silicon levels. The results suggest that serum silicon levels are elevated in many women with silicone gel breast implants. The chemical species involved and kinetics of this elevation remain to be determined.
Breast Implants↗
Immunopathologic effects of silicone breast implants.
Silicone-gel breast implants have been associated with a myriad of autoimmune and connective tissue disorders by anecdotal reports and small observational series. To date, no prospective epidemiologic studies have been done to substantiate these observations, but an increasing body of literature is being developed and older studies are being recognized that point to immunotoxic or inflammatory effects of these breast implant components. The development of disease due to implants would depend on the interaction of genetic host factors so that only a few patients would potentially be at risk. Based on the example of other chemically mediated disorders, such as scleroderma in association with silica exposure, latency periods of more than 30 years before disease develops may be possible. Herein we review studies on silicone and immunity.
Animals↗
Silicone breast implant-associated scarring dystrophy of the arm.
BACKGROUND: Breast implants have been known to rupture after trauma or closed capsulotomy with spread of the gel down the arm or abdominal wall. Nodular foreign-body granulomatous reactions have been reported in these cases. We report the unique occurrence of significant overlying scarring and ulceration following silicone gel migration down the affected arm. OBSERVATIONS: A 47-year-old woman experienced rupture of her right silicone gel implant with migration of the silicone down her arm 10 years before our examination. Skin changes with atrophic hidebound scarring and ulceration slowly progressed over the last 7 years. Radiographs and magnetic resonance imaging scans demonstrated material consistent with silicone in the soft tissues. CONCLUSIONS: Silicone is not an inert substance and can rarely result in devastating local tissue destruction where migration has occurred. The possibility of significant silicone gel migration should be considered during evaluation of patients with ruptured implants.
Arm↗
Antibodies to collagen: comparative epitope mapping in women with silicone breast implants, systemic lupus erythematosus and rheumatoid arthritis.
Women with silicone breast implants have a significantly increased frequency of antibodies to collagen types I and II. To characterize the specificity of these antibodies, 70 women without a specific autoimmune disease, according to the criteria of the American College of Rheumatology, but who had silicone breast implants were studied for the presence of serum antibodies to native and denatured human types I and II collagen by ELISA. Positive sera were further studied by immunoblotting using peptides derived by cyanogen bromide digestion of the collagens. Samples of 82 women with systemic lupus erythematosus (SLE), 94 women with rheumatoid arthritis (RA), and 133 healthy controls were studied concurrently. There was a high frequency of autoantibodies to collagen in each of the study groups when compared to the healthy controls. However, and of particular interest, the epitope specificity of the autoantibodies differed markedly. Sera from women with silicone implants reacted strongly in an individual-specific manner with multiple peptides of type I collagen, whereas sera from women with SLE and RA reacted only weekly with a restricted range of peptides of type I collagen. Sera from women with RA reacted strongly with multiple peptides of type II, whereas sera from women with silicone implants or SLE reacted only weakly. The reactivity of women with silicone implants suggests that silicone or its biodegradation products can act as adjuvants in situ to enhance the immunogenicity of type I collagen, or protein-silicone conjugates.
Arthritis, Rheumatoid↗
Immunotoxicity of silicone: implications of oxidant balance towards adjuvant activity.
A variety of mechanisms can be proposed to explain the potential effects of silicone and silicone by-products on the immune response. In this paper, we discuss information on the chemistry of silicon and silicone gels/elastomers, and the manufacture of silicone breast implants as they pertain to the bioreactivity of silicone. Moreover, with reference to silicone-mediated human adjuvant disease, an overview of experimental adjuvant-induced arthritis is presented; comparisons with graft-versus-host disease and chemically induced autoimmunity then follow. Particular attention is paid to similarities in the characteristics of silicone and classic lipid adjuvants. For example, macrophage activation is presumed to be a central event in silicone-induced autoimmunity. Since those genes uniquely expressed in macrophages activated by plastic adherence are similar to those induced by lipopolysaccharide, adherence to silicone rubber may initiate an inflammatory response by the same mechanism. Macrophage effects would also include the erosion of implants through the generation of oxidants and localized pH changes. The degradation products of silicone are also implicated in the adjuvant effects of silicone implants. There is evidence to suggest that oxidants produced by inflammatory cells preferentially inactivate CD8+ suppressor T cells. This could then lead to an inflammatory state, perhaps through oxidant-induced transcription factors such as NF-kB, resulting in a long-term pro-oxidant imbalance that manifests itself as a breakdown in immunological self-tolerance. The authors hypothesize that autoreactivity following oxidant stress evolved to enhance inflammatory repair mechanisms after tissue, cell or molecular damage by oxidants.
Animals↗
Autoantibodies and clinical rheumatic complaints in two children of women with silicone gel breast implants.
Considerable interest and efforts are directed at determining the extent to which silicone gel breast implants may contribute to the risk of developing autoimmune disease. There is also comparable interest in determining the extent to which silicone may alter the natural history of an established autoimmune disease. Recently, there has been concern over the possibility that children of women with silicone breast implants might somehow be adversely affected because of either trans-mammary or trans-placental delivery of silicone during either breast feeding or pregnancy. Herein, we describe two children of mothers with silicone breast implants, both female, aged approximately 3 and 9 years, both of whom had long-standing myalgias that were unexplained and did not fit current clinical criteria for juvenile arthritis. Both were found to have positive antinuclear antibodies. Additionally, the 9-year-old girl was found to have a significantly high titer of antibodies against denatured human type II collagen; indeed, her titer was six standard deviations above the mean for normal controls. There have been numerous previous studies which have documented an adverse impact of trace metals, chemicals and some medications on the morphologic and neurologic development of children exposed in utero. Much less information exists on potential toxicity experienced by a neonate through breast feeding, although examples of toxic transmission have been reported. In Western Europe, but not the United States, women with silicone breast implants are advised not to breast feed. Further research should address these concerns and, in particular, women with silicone breast implants, with evidence of leakage or rupture, should refrain from breast feeding until further data are obtained.
Autoantibodies↗
Remission of sarcoidosis following removal of silicone gel breast implants.
We report herein a patient with debilitating multisystem sarcoidosis. Interestingly, dermal lesions and enlarged lymph nodes resolved and her clinical condition dramatically improved following removal of silicone gel breast implants. Of note, the capsular tissue surrounding the breast implant demonstrated a granulomatous foreign-body response. The potential harmful effects of silicone may include an acceleration of an already existing hypersensitivity response.
Adult↗
Anti-collagen autoantibodies are found in women with silicone breast implants.
There have been several anecdotal reports that silicone breast implants are associated with an increased incidence of autoimmune disease. Based upon these data as well as the theoretical potential of silicon and silicone immune interactions, we hypothesized that an immune response to a silicone breast implant would include host reactivity against components of the microenvironment within the implant milieu. To test this hypothesis, we obtained detailed histories and performed examinations of 57 consecutive, self-referred patients concerned about their breast implants. Eleven of these women were excluded for various reasons including previous exposure to bovine collagen. The remaining 46 women, as well as 45 normal women of approximately the same age and living in the same geographic region, were tested using a sensitive ELISA for the presence of autoantibodies to human native type I collagen, denatured type I collagen, native type II collagen and denatured type II collagen. Known positive and negative sera were included in all assays and the ELISA was performed and interpreted blindly. Positive sera were defined as an ELISA value of three standard deviations above the mean of the normal controls. Using these stringent criteria, there was a statistically significant incidence of antibodies to collagen in women with silicone breast implants. In fact, 35% of women with silicone breast implants had such antibodies; this is higher than we have observed in any other autoimmune disease and is similar to that of chronic erosive rheumatoid arthritis. We believe that silicone breast implants, in genetically susceptible hosts, may pose a significant risk for immunopathology.
Adult↗
Silicon and silicone: theoretical and clinical implications of breast implants.
In the past 10 years, there have been multiple published reports associating silicone breast implants with scleroderma, morphea, SLE, rheumatoid arthritis, CREST syndrome and "human adjuvant disease." The alleged offending material, silicone, is a synthetic polymer containing a silicon-oxygen backbone. Beginning with the heating of SiO2 in the presence of carbon, elemental silicon is produced. Methylchloride is added and the resulting product is hydrolyzed to form low molecular weight prepolymers which are linked to form linear silicone polymers and cross-linked to yield silicone rubbers or elastomers. The polymeric and hydrophobic characteristics of silicone and the presence of electrostatic charges and organic sidegroups make silicone a potentially ideal immunogen, leading to cross-reactivity with autoantigens. Silicon is an essential constituent of proteoglycans which theoretically could result in immunological cross-reactions between silicone and connective tissues. Although the literature contains numerous examples of silicone-associated autoimmune disease, there is no consistent pattern of immunological abnormalities observed. There are, however, some intriguing and interesting observations. Further large-scale studies are needed to determine if a link between silicone exposure and autoimmunity exists. Also, since the inducing events of autoimmune diseases are unknown, studies on silicone could provide a model for autoimmune diseases associated with toxicological factors.
Adult↗
Chromosome localization and RFLP analysis of PDC-E2: the major autoantigen of primary biliary cirrhosis.
Patients with primary biliary cirrhosis are well known for the presence of titer antibodies against dihydrolipoamide acetyltransferase, the E2 subunit of the pyruvate dehydrogenase complex. We have taken advantage of a cDNA probe for dihydrolipoamide acetyltransferase to explore the possibility of polymorphism of the E2 subunit by probing genomic DNA from 38 patients with primary biliary cirrhosis and 26 healthy controls. To detect restriction fragment length polymorphism, DNA was digested with ten specific restriction enzymes that often detect polymorphism, including Bam HI, Bgl II, Eco RI, Hind III, Hinf I, Msp I, Pst I, Pvu II, Rsa I and Taq I. A Taq I polymorphism was found in 19 of 38 patients with PBC and 6 of 26 normal controls. In addition, using fluorescence in situ hybridization, the gene for dihydrolipoamide acetyltransferase was mapped on human chromosome 11 band q23.1. Interestingly, this region of the long arm of chromosome 11 is often associated with cytogenetic abnormalities, including translocations.
Autoantigens↗
The identification and cloning of the murine genes encoding the liver specific F alloantigens.
The liver specific F alloantigen is a highly conserved abundant protein found in hepatic cytoplasm; smaller amounts are detected in renal tubule cells and the perikaryon cells of the central nervous system. Although the biological function of the F alloantigen is unknown, the immune response to F has been extensively studied as a murine model of tolerance and autoimmunity. Murine F exists in two allelic forms, designated F type 1 and type 2, each of approximately 43 kDa. The immune response to the allotypic form is restricted to mouse strains of I-Ak. Responding strains immunized with allotypic F break tolerance and produce precipitating antibody that reacts with both allelic forms, i.e., immunogen and self. Thus an autoantibody is produced. Using the previously isolated rat F cDNA as a probe, we report the cloning and sequencing of the two murine F allotypes. These two alleles are nearly homologous except at the extremes of the coding sequence. There are a number of regions within the F sequence that are similar to peptides that interact specifically with I-Ak. In particular, there is a sequence near the carboxy terminus, where the two allotypes differ, that has homology to the I-Ak restricted malarial antigen peptide of the ring-infected erythrocyte surface antigen (RESA).
Amino Acid Sequence↗