Re: the name of the silicone test, neurologist, MRI

That's a different one, but good find! An allergic reaction to silicone makes sense to me.

Here's a copy/paste of that one I found. Not sure how great it will look. I was able to open the pdf again when I tried. Maybe it's the adobe version? I'll include the link:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC368392/pdf/cdli00006-0089.pdf


CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY, Nov. 1994, p. 689-695 Vol. 1, No. 6
1071-412X/94/$04.00+0
Copyright © 1994, American Society for Microbiology
Silicone-Specific Blood Lymphocyte Response in Women
with Silicone Breast Implants
EMMANUEL A. OJO-AMAIZE,1* VICTOR CONTE,2 HUN-CHI LIN,1 ROBERT F. BRUCKER,2
MELKON S. AGOPIAN,1 AND JAMES B. PETER'
Specialty Laboratories, Inc., Santa Monica, California 90404-3900,' and
Balco Laboratories, Inc., Burlingame, Califomia 940102
Received 20 May 1994/Returned for modification 29 June 1994/Accepted 20 July 1994
A blinded cross-sectional study was carried out with 99 women, 44 of whom had silicone breast implants.
Group I consisted of 55 healthy volunteer women without breast implants; group II comprised 13 volunteer
women with breast implants or explants who felt healthy; group III comprised 21 volunteer women with breast
implants who had chronic fatigue, musculoskeletal symptoms, and skin disorders; and group IV comprised 10
women who had their prostheses explanted but still presented with clinical symptoms similar to those of the
women in group III. Proliferative responses of peripheral blood mononuclear cells from all 99 women were
measured by [3H]thymidine uptake after exposure to SiO2, silicon, or silicone gel. The levels of proliferative
responses were expressed as stimulation indices, which were obtained by dividing the counts per minute of
stimulated cells by the counts per minute of unstimulated cells. Abnormal responses to SiO2, silicon, or silicone
gel were defined as a stimulation index of >2.8, >2.1, or >2.4, respectively. Abnormal responses were observed
in 0%1 of group I, 15% of group 1, 29%o of group Ill, and 30%o of group IV (P < 0.0005 for group I versus groups
II and IV). Thirty-one percent of symptomatic women with silicone gel breast implants had elevated serum
silicon levels (>0.18 mg/liter); however, there was no significant correlation between abnormal cellular
responses and silicon levels in blood serum, type of implant, time since first implantation, prosthesis
explantation, number of implants, or report of implant leakage or rupture. Flow cytometric and cell depletion
analyses showed that the responding cells were CD4+ T cells, with no apparent contribution from the CD8+
T-cell population. Our demonstration that silicon-specific T-cell responses are observed in twice as many
symptomatic as asymptomatic women exposed to silicone breast implants suggests that cell-mediated
immunity plays a role in the development of abnormal immune reactions associated with silicone and provides
a new, apparently specific screening blood test. Whether the activity observed in asymptomatic women is
predictive of symptom development is under prospective study.
The term silicone refers to a group of silicon-containing
compounds, which include fluids, gels, rubbers, sponges,
foams, and resins (1). Although silicone was originally regarded
as being inert in the human body, its polymeric and
hydrophobic characteristics and the presence of electrostatic
charges and organic side groups render silicone a potentially
ideal immunogen (32). Several reports suggest that silicone
products are associated with various complications that may
involve an immune reaction to silicone (4, 11, 16, 31). Approximately
1 to 2 million women in the United States have had
silicone breast implants inserted for reconstruction or augmentation
mammoplasty; some of these women are reported to
have developed a systemic autoimmune disease (19, 26, 29).
Presently, it is uncertain which complications have a causeand-
effect relationship and which represent coincidental findings
(26). There is further confusion in distinguishing between
nonspecific local reactions and reactions that have an immunological
basis (8). In view of the fact that silica mining is
thought to predispose individuals to certain autoimmune diseases,
systematic immunologic studies of women with silicone
gel implants are needed to assess any possible role of cellmediated
immunity in the clinical complications of silicone
breast implants. Our studies reported herein were directed to
the search for silicon(e)-specific T cells in the circulation of
* Corresponding author. Mailing address: Specialty Laboratories,
Inc., 2211 Michigan Ave., Santa Monica, CA 90404-3900. Phone: (310)
828-6543, extension 310. Fax: (310) 828-6634.
women with silicone breast implants and to the possible
correlation of such reactivity with various complications associated
with silicone medical devices.
MATERIALS AND METHODS
Reagents. Lithium sulfate (Li2SO4), nickel sulfate hexahydrate
(NiSO4 -6H20), zirconyl chloride hydrate (ZrOCl2),
mercuric chloride (HgCl2), chromic trioxide (CrO3), magnesium
sulfate (MgSO4), and silicon dioxide (Si02) were purchased
from Sigma Chemical Company (St. Louis, Mo.). Other
reagents and sources included beryllium sulfate tetrahydrate
(BeSO4 *4H20) (Aldrich Chemical Co. Inc., Milwaukee,
Wis.), elemental silicon (Si) and silicone gel (Spex Industry,
Edison, N.J., and Mentor Corporation, Santa Barbara, Calif.),
RPMI 1640 medium and Hanks' balanced salt solution (HBSS)
(Irvine Scientific, Santa Ana, Calif.), Ficoll-Paque in vitro
lymphocyte isolation medium (Pharmacia, Piscataway, N.J.),
penicillin-streptomycin mixture (GIBCO Laboratories, Grand
Island, N.Y.), and pooled human AB serum (Gemini Bioproducts,
Inc., Calabasas, Calif.). Fluorescence-activated cell sorter
lysing buffer, phycoerythrin-labeled monoclonal antibody
(MAb) Leu2a (CD8), and fluorescein isothiocyanate-labeled
MAb Leu3a (CD4) were purchased from Becton Dickinson
(San Jose, Calif.). An AIS MicroCellector for the selection of
T-cell subsets was obtained from Applied Immune Sciences,
Inc. (Menlo Park, Calif.).
Blood donors. In a blinded cross-sectional study, peripheral
blood was obtained by venipuncture from 55 healthy women
689
690 OJO-AMAIZE ET AL.
TABLE 1. Characterization of 44 women with silicone gel breast implants
Group Clinical characteristics No. of No. with the following type of implant:
subjects Silicone gel Lumena Memeb Unknown
I No implants, healthy 55
II Implants or explants, well, asymptomatic 13 8 3 1 1
III Implants, symptomatic (chronic fatigue, musculoskeletal 21 13 3 1 4
symptoms, autoimmune disease)
IV Explants, symptomatic (chronic fatigue, musculoskeletal 10 7 3 0 0
symptoms, autoimmune disease)
a Silicone inside and saline outside.
b Polyurethane foam coated.
who did not have breast implants (group I) and from 44 women
with silicone gel breast implants (groups II to IV). Informed
consent was obtained in accordance with institutional guidelines.
Of the 13 asymptomatic women, 4 had explanted their
breast prostheses and the other 9 still had their implants in
place and felt well (group II). Group III consisted of 21 women
with breast implants who had various symptoms, including
fatigue, fibromyalgia, insomnia, skin disorders, respiratory
complaints, headache, joint pain, muscle cramps, arthritis,
short-term memory problems, allergies, arrhythmia, and anemia.
Group IV comprised 10 women who had their breast
implants removed because of overt connective tissue diseases.
All of these women (groups II to IV) filled out questionnaires
about their medical history; they were referred by plastic
surgeons and primary-care physicians and through individual
breast implant support groups. Each woman provided detailed
information with regard to date of placement of all implants,
indications for implantation, type(s) of implant, reported overt
leakage or rupture, and duration, types, and severity of symptoms.
Measurement of silicon levels in blood serum. Serum samples
were analyzed by using an inductively coupled plasma
atomic emission spectrometer (Applied Research Laboratories,
Dearborn, Mich.). The samples were introduced to the
argon plasma by a peristaltic pump (Gilson Medical Electronics,
Inc., Middleton, Wis.) and an auto sampler (Gilson).
Details of the methodology and the instructions given to
subjects were essentially as previously described (9, 10, 20).
Preparation of lymphocytes. Peripheral blood mononuclear
cells (PBMC) isolated from heparinized venous blood by
Ficoll-Hypaque gradient centrifugation (3) were washed three
times with Hanks' balanced salt solution before determination
of viability by the trypan blue dye exclusion method. Cells
resuspended in complete culture medium (20% heat-inactivated
pooled human AB serum, 2 mM L-glutamine, 2 mM
N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid [HEPES],
and 1% penicillin-streptomycin [10,000 U/ml]) were adjusted
to 2 x 106/ml.
Selection of T-lymphocyte subsets. The AIS MicroCellector
Cell Culture Flask System was used to negatively select either
CD4+ or CD8+ cells according to manufacturer's instructions.
In the MicroCellector Cell Culture Flask System, MAbs are
permanently bound to the surface. When blood cells are
added, the immobilized ligands bind to surface antigens of the
targeted cells; cells not bearing the recognized antigens remain
free in suspension. A quantity of 4 x 107 PBMC was added to
either the AIS CD4 T-25 flask (MAb Leu3a bound; for
depletion of CD4+ cells and selection for CD8+ cells) or the
CD8 T-25 flask (MAb Leu2a bound; for depletion of CD8+
cells and selection for CD4+ cells). After incubation for 1 h at
room temperature (RT) on a flat nonvibrating surface, nonadherent
cells were removed, washed twice in complete medium,
counted, and analyzed by flow cytometry.
Flow cytometric analysis of T-lymphocyte subsets. Following
lysis of any remaining erythrocytes, P13MC were stained with a
mixture of phycoerythrin-labeled MAb CD8 and fluorescein
isothiocyanate-labeled MAb CD4. Stained cells were analyzed
on a FACScan cytometer (Becton Dickinson). Lym.phocytes
were gated by forward and right-angle light scattering.
Antigens. Si02 was prepared in concentrated phosphoric
acid (H3P04). A 2 mM stock solution was prepared and stored
at RT until used for assay at final concentrations of 10, 1, and
0.1 ,uM in complete culture medium.
A stock solution of silicon dissolved in H20 at a concentration
of 1 mg/ml was stored at RT until used for assay at final
concentrations of 10, 1, and 0.1 ,ug/ml in complete culture
medium.
A stock solution of 1 g of silicone gel dissolved in hexane to
yield 100 mg/ml was stored at RT until used for assay at final
concentrations of 10, 1, and 0.1 jig/ml in complete culture
medium.
Lymphoproliferation. Lymphocytes (2 x 105/0.1 ml of complete
culture medium) were dispensed in quadruplicate into
96-well round-bottomed microtiter plates, and antigens (0.1 ml
per well) were added in complete culture medium. Nonstimulated
control wells contained 0.1 ml of cells and 0.1 ml of
complete culture medium. Cultures were maintained in a
humid incubator at 37°C in an atmosphere of 5% CO2 for
periods shown in preliminary experiments to be optimal (5
and 7 days). At 4 h before harvest, the cultures in each
well were pulsed with 1 ,uCi of tritiated thymidine (specific
activity, 719.5 mCi/mg; Dupont, Wilmington, Del.). Cells harvested
onto glass fiber filters (Packard, Downers Grove, Ill.)
with a 96-well automatic cell harvester (TOMTEC, Hamden,
Conn.) were counted directly on a Matrix 9600 direct beta
counter (Packard). Data were expressed as the stimulation
index (SI) (counts per minute for stimulated wells/counts per
TABLE 2. Establishment of normal reference range for
determination of degree of stimulation with three forms
of silicon in healthy women without breast implants
Type of No. of Mean SI + 3 SD at: Established
silicon subjects per SI cutoff group 0.1 pLM 1.0 ,uM 10 ,uM value
Si02 40 2.4 2.9 3.1 2.8
Silicona 15 2.9 2.0 1.4 2.1
Silicone gela 15 3.0 1.8 2.3 2.4
a Elemental silicon and silicone gel were used in microgram concentrations
(0.1, 1.0, and 10 ,ug/ml) on cells of the same 15 healthy women.
CLIN. DIAGN. LAB. IMMUNOL.
T-CELL RESPONSE IN WOMEN WITH SILICONE BREAST IMPLANTS 691
TABLE 3. Silicon-specific T-cell proliferative response in women
with silicone gel breast implants
Groupa sNuobj.ecotfs No.T-(ce%l)l wrietshpoanbsneortomal
silicon(e)b
I 55 0(0)
II 13 2 (15.3)C
III 21 6 (28.6)
IV 10 3 (30.0)
a The groups are characterized in Table 1.
b Individuals with SI values greater than the cutoff values shown in Table 2 at
any concentration, at any of the two optimal time points (5- or 7-day culture),
and to any of the three forms of silicon.
c One of the two women with an abnormal cellular response to elemental
silicon had her breast implant in place, and the other had had hers explanted.
Both were healthy at the time of study.
minute for unstimulated control cultures) ± standard error of
the mean.
Determination of dose-response curve for response to stimulation
with SiO2, silicon, or silicone gel. Viable cells, adjusted
to 2 x 106/ml, were dispensed in 0.1-ml volumes (2 x 105 cells
per well) into microtiter wells and challenged with different
concentrations of SiO2, silicon, or silicone gel in O.1-ml volumes.
The cultures were incubated for 5 or 7 days. At 4 h
before the end of the culture period, the cultures were pulsed
with 1 ,uCi of [3H]thymidine. Blastogenic responses were
determined as described above.
Determination of kinetics of secondary response. Viable
cells, adjusted to 2 x 106/ml, were dispensed in O.1-ml volumes
(2 x 105 cells per well) into microtiter wells and challenged
with different concentrations of SiO2, silicon, or silicone gel in
0.1-ml volumes. The cultures were incubated for various
periods of time (1, 3, 5, 7, and 9 days). At 4 h before the end
of each culture period, the cultures were pulsed with 1 ,uCi of
[3H]thymidine. Proliferative responses, expressed as SIs, were
determined as described above.
Evaluation of antigen specificity of silicon-reactive cells.
The antigen specificity of silicon-reactive cells was evaluated by
testing a battery of related metal salts and comparing the
results with those for silicon, SiO2 and silicone gel. The salts,
which were tested at three different final concentrations (0.1, 1,
and 10 ,uM), included BeSO4, CrO3, Li2SO4, NiSO4, ZrOCl2,
HgCl2, and MgSO4. SIs after 5 or 7 days of culture were
measured as described above.
Establishment of SI cutoff values for determination of
abnormal response to Si02, silicon, or silicone gel. An abnormal
or positive response is defined as a peak SI of >2.8 for
SiO2, >2.1 for silicon, or >2.4 for silicone gel. These values are
based on the blood mean peak SI plus 3 standard deviations for
40 healthy women (SiO2), 15 healthy women (silicon), and 15
healthy women (silicone gel).
Statistical analysis. All values are means ± standard errors
of the means. Statistical comparisons were made with Student's
t test.
RESULTS
Characterization of women with silicone breast implants.
The 99 women who voluntarily participated in the blinded
study were divided into four groups at the completion of the
study. Group I consisted of 55 healthy women without breast
implants, group II comprised 13 healthy women, group III
consisted of 21 women with breast implants who had chronic
fatigue and musculoskeletal symptoms, and group IV com-
8-
c
-o
C
C-
0cc
E ._"
co
6-
4-
I
n=55
II
n=13
m
n=21
IV
n=10
Group Number
FIG. 1. Silicone-specific T-cell response profile of women with
silicone gel breast implants. The highest response (SI) obtained for
each woman in each group at any of the three concentrations tested
against any of the three forms of silicon is shown. Group I represents
healthy controls, group II represents asymptomatic women with breast
implants or explants, group III represents symptomatic women with
breast implants, and group IV consists of symptomatic women who
have had their silicone breast prostheses explanted. All the women
(groups I to IV) had normal responses to the T-cell mitogen phytohemagglutinin
(SI > 50). The woman with the highest SI value in group
III is the same woman whose results were used to generate the results
shown in Fig. 4. This woman is subject no. 4 in Table 4.
prised 10 women who had their prostheses explanted but still
presented with clinical symptoms similar to those of the
women in group III (Table 1).
Establishment of normal reference range for assessment of
cellular response to stimulation with three forms of silicon. Of
the 55 healthy women without implants used to establish the
normal reference range, 40 were used for SiO2 and the other
15 were used for silicon and for silicone gel. The mean SIs +
3 standard deviations for each of three concentrations of each
antigen are shown in Table 2. Because the results did not differ
significantly, the average of the standard deviations at all three
concentrations for each antigen was used as the cutoff value for
that antigen (Table 2).
Silicon-specific and T-cell mitogen proliferation response in
women with silicone gel breast implants. Abnormal siliconspecific
T-cell proliferative responses were observed in 0% of
group I, 15% of group II, 28.6% of group III, and 30% of
0
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VOL. 1, 1994
692 OJO-AMAIZE ET AL.
4.
w
CO)
+1
0
2
E,
3.
2
1
0,
0 .1 1 10 100 1000
SbC Concentraon (M)
FIG. 2. Dose-dependent proliferative response of PBMC from women with silicone breast implants to stimulation with SiO2. PBMC from three
women with silicone breast implants were challenged with various concentrations of SiO2. SEM, standard error of the mean. Symbols: A, a woman
with an abnormal cellular response to SiO2 (SI > 2.8); O, a woman with a normal (intermediate) response to Si02; 0, a woman with a normal
(low) response to Si02.
group IV (Table 3). The responses were significantly higher in
groups II, III, and IV than in group I (group I versus group II,
P < 0.05; group I versus group III, P < 0.0005; and group I
versus group IV, P < 0.0000001). The average SI of each
individual woman in each group is shown in Fig. 1. All the
patients responded normally (SI > 50) to the T-cell mitogen
phytohemagglutinin.
Dose-dependent proliferative response of PBMC from
women with silicone breast implants to stimulation with Si02.
PBMC from three women were used to establish the doseresponse
curve. In a prior experiment, one of these women had
an abnormal response to 1 ,uM SiO2, and the other two had
responses below the cutoff value for SiO2. SiO2 concentrations
of 0.1 and 1.0 ,uM induced higher levels of responses than
concentrations of >50 ,uM (Fig. 2). Similarly, concentrations
of 0.1, 1.0, and 10 ,ug/ml for silicon and silicone gel induced
optimal levels of responses (data not shown). The data indicate
that responses to one or more forms of silicon at various
concentrations can occur.
Kinetics of proliferative response of PBMC from a woman
with silicone breast implants to stimulation with SiO2, silicon,
or silicone gel. PBMC from a woman who had previously been
determined to have abnormal SIs for stimulation with Si02 and
silicone gel were used for the kinetics experiment. Following
stimulation with 0.1, 1.0, or 10 ,IM Si02 or with 0.1, 1.0, or 10
j,g of silicon or silicone gel per ml, cells were cultured for
various periods of time (1 to 9 days). Both forms of silicon
induced maximal responses between days 5 and 7 (Fig. 3), with
the greatest response being on day 7. These results are similar
to those for the beryllium-induced T-cell response, which
showed that either of two optimal time points is appropriate
for determining the response to beryllium (15, 18, 23). An
individual with SI values greater than the cutoff values for each
of the antigens, at any of the three concentrations and at any
of the two optimal time points (5- or 7-day culture), is regarded
as having an abnormal T-cell proliferative response to silicon.
Specificity of the silicon-reactive PBMC. PBMC from a
symptomatic woman with silicone breast implants who was
previously shown to have an abnormal response to stimulation
with Si02 were used to demonstrate that a metal-specific
immune response to Si02 could be documented. All of the
antigen metals tested (except Si02 and silicone gel) failed to
induce significant responses in the silicone-sensitized woman
(Fig. 4). Although the particular woman used for this experiment
did not respond to elemental silicon, some of the women
in groups II, III, and IV responded to elemental silicon (Table
4).
Effect of T-cell subset depletion. After depletion with the
AIS MicroCellector Cell Culture Flask, two-color immunofluorescence
and flow cytometry demonstrated that the siliconreactive
cells possess the CD4+ phenotype. No activity was
found in the CD8+ population of T cells (Table 5).
Serum silicon levels. Four of 13 (31%) symptomatic women
with silicone gel breast implants, 1 of 7 (14%) symptomatic
women who had had their prostheses explanted, 0 of 4 (0%)
asymptomatic women with implants, and 0 of 8 (0%) controls
had elevated levels of silicon in serum (>0.18 mg/liter).
DISCUSSION
In spite of the widespread use of silicone and related
materials in humans, there have been very few systematic
studies on the immunological effects of silicone. Although
silicone is known to induce inflammatory responses (8, 16) and
lymphadenopathy and giant-cell granulomas (7, 21), a specific
cellular response to silicone has never been demonstrated by
standard immunological assays. On the other hand, specific
T-cell immune responses to light metals were observed in
several studies (13, 22, 23, 30). The present report shows, for
the first time, that silicon(e) can act as a specific sensitizing
antigen in vivo, leading to a silicon(e)-specific immune response
in vitro as measured by [3H]thymidine uptake by T cells
responding to stimulation with either Si02, silicon, or silicone
gel.
Women with silicone breast implants are known to have
several types of autoantibodies against different self antigens
(5, 25-27, 29, 32). Our data showing the involvement of CD4+
cells in silicone-induced immune reactions suggest that at least
one of the mechanisms by which certain individuals with
silicone prostheses produce autoantibodies could be via the
CLIN. DIAGN. LAB. IMMUNOL.
T-CELL RESPONSE IN WOMEN WITH SILICONE BREAST IMPLANTS
w
-H
c
Co
0
C
E
co
9.
8.
7.
6.
5.
4
3
2
I
0 2 4 6 8
Duration in Culture (days)
10
FIG. 3. Kinetics of secondary proliferative response of PBMC from a woman with a silicone breast implant to stimulation with SiO2, silicon,
or silicone gel. PBMC were from a woman with a silicone breast implant who had an abnormal cellular response to Si02 (O), an abnormal response
to silicone gel (A), and a normal response to silicon (0). SEM, standard error of the mean. Results shown are peak SIs at any one of the following
SiO2 concentrations: 0.1, 1.0, or 10 ,uM.
amplification of T-cell help for autoreactive B cells. The
finding that more symptomatic silicone implant-exposed
women developed abnormal T-cell responses to silicone (compared
with asymptomatic implant women) (Table 3) is consistent
with the notion that autoimmune reactions prevalent
among this group of women may be associated with silicon
materials. The demonstration of 15% positivity in the asymptomatic
group (group II) suggests that all asymptomatic
women who are positive must be monitored over time and that
all women with silicone breast implants and individuals with
other silicone prostheses should be tested for a hypersensitivity
reaction to silicon(e). In support of this notion is the observa-
36
32
2 28
+1 24
C')
X 20 0
- 16 C
0
X 12
EE 8
n
4 m xxx .S
BeS: 4 CrO3 U2SO4 MgSO4 NiSO4 HgC12 ZrOC12 Silicon Sil gel SO2
FIG. 4. Specificity of the response to silicone. PBMC were from a symptomatic woman with a silicone breast implant who had an abnormal
response to SiO2 and silicone gel but a normal response to silicon and the rest of the metal salts. This was the same woman with the highest SI
value in group III, as shown in Fig. 1. SEM, standard error of the mean. Results are shown as peak SIs at any one of the three concentrations (0.1,
1.0, and 10 p.M) and any one of the two time points (5- or 7-day culture).
VOL. 1, 1994 693
694 OJO-AMAIZE ET AL.
TABLE 4. Responsiveness of 11 women with abnormal response
to different forms of silicon
SIb with:
Groupa Subject SiO2 at (>M) Silicon at Silicone gel at
no. (Rg/ml): (Rg/ml):
0.1 1.0 10.0 0.1 1.0 10.0 0.1 1.0 10.0
II 1 2.7
2 3.6
III 3 4.3 3.1 2.9
4 33 9.6 7.7 4.8
5 2.2
6 2.9 4.5
7 2.8
8 7.4 4.3
IV 9 3.1
10 3.9 2.4
11 3.8
a The groups are characterized in Table 1.
b The highest SI value obtained for each subject with either 5- or 7-day culture.
tion that only about 5% of all beryllium-sensitized individuals
develop chronic beryllium disease, which is found only in
beryllium-sensitized individuals (12, 15, 18, 23). In other words,
beryllium sensitization is a necessary but not sufficient factor
for development of beryllium disease. This may also be true for
silicon. The fact that some implant-exposed individuals responded
to all three forms of silicon whereas others responded
only to one, two, or none of the silicon forms may reflect
differences in either the level of in vivo priming, type of
implant, genetic susceptibility, active immunosuppression, or
tolerance. The few implant patients with symptoms who
showed abnormal T-cell responses to silicon materials were not
clinically different from the symptomatic patients who showed
normal responses. Whether this is related to the small number
of patients or to the genetic background of the individuals will
be addressed in future studies involving a larger number of
patients.
Specific antibodies to silicone were observed in the sera of
only a small proportion (1.7%) of 249 women with silicone
breast implants (14). The observation that cell-based reactivity
with silicone is more prevalent than antibody-based reactivity
is consistent with the observation that for a related light metal,
beryllium (2, 12, 15, 17, 18, 23, 24, 28), cell-mediated immunity
as measured by T-cell proliferation is more common than
beryllium-specific antibodies (6). In addition, the demonstration
of antibody reactivity with metals is quite tedious because
of the complexities of binding of light-metal antigens to
TABLE 5. Characterization of silicon-specific lymphocytes
according to phenotype
% of cells
T-cell expressing T-cell Level of silicon-specific
population subset phenotypea: T-cell proliferative
response (SI)b ± SD
CD4 CD8
CD4 depleted 8.8 91.2 0.9 ± 0.2
CD8 depleted 96.3 3.7 4.0 ± 0.6
a Percentages of cells expressing the designated antigens following depletion
with the AIS MicroCellector Cell Culture Flask System and subjection to flow
cytometric analysis.
b Each cell population was stimulated with 1.0 ,ug of silicone gel for 7 days or
left unstimulated. Cells were obtained from one of the six women in group III
with an abnormal T-cell proliferative response to silicone gel.
polystyrene plates. In contrast to the small number (1.7%) of
symptomatic women with silicone breast implants identified to
be silicone antibody positive by the silicone antibody test (14),
we have identified 25% (11 of 44) of such women to be silicone
hyperreactive by the T-cell proliferation assay (Table 3). This
proportion must, of course, be considered an approximation
until similar studies with larger numbers of subjects are
conducted.
Our data demonstrating that CD4+ T cells are the target
cells for silicon(e) are consistent with previous reports on the
involvement of CD4+ T cells in the immune response against
a related light metal, beryllium (18, 24).
In conclusion, the silicon(e)-specific T-cell proliferation test,
compared with a silicon-specific antibody test, is less cumbersome
to perform, is more specific and sensitive, and permits
the gathering of information on an individual's cellular abnormal
reaction to either elemental silicon, SiO2, or silicone gel.
ACKNOWLEDGMENTS
We thank Raksha Inamdar, Jesusa Arevalo, and James Valente for
their technical contribution, Rose G. Yesowitch for preparing the
manuscript, Sharon Hunt Gerardo for her critical review, and Brian
Goldman for preparing and reviewing the systemic health questionnaires.
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