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Fo Autoimmune markers were analyzed in the sera of autistic
Methods:
and normal children, but the cerebrospinal fluid (CSF) of some autistic
children was also analyzed. Laboratory procedures included enzyme-
linked immunosorbent assay and protein immunoblotting assay.
For mass reproduction, content licensing and permissions contact Dowden Health Media.
Annals of Clinical Psychiatry
player. The latter should be targeted by immunotherapy account for only a smaller percentage (≤10%) of autism
to help children with autism. cases, whereas the remaining, larger percentage (≥90%)
of cases would be sporadic due to nongenetic factors.4
Keywords: autism, viruses, autoimmunity, CNS infec- The sporadic form might be acquired from exposure
tions, immunotherapy, developmental disorders, metal to environmental factors such as viruses, vaccines, or
allergy, neurotoxicity, immunotoxicity chemical toxins and other unknown factors. In this
article, the author summarizes his laboratory research
to date and reviews scientific data that lend credibility
I n tro d u c t i o n to a virus-induced autoimmune mechanism of patho-
genesis for autism. The knowledge resulting from auto-
Although autism was first described by American psychi- immunity research has direct clinical relevance to the
atrist Leo Kanner more than 60 years ago, the cause and overall health and recovery of autistic children. Accord-
treatment of this brain disorder still remains poorly un- ingly, the author suggests that autoimmunity is a very
derstood. Now, autism is no longer regarded as a simple important target of therapeutic development for autism,
developmental disorder but rather a biological disorder of and offers a novel approach to immunotherapy with use
complex etiology and heterogeneity.1-4 Autism is defined of natural immunomodulators.
not by etiology or pathology but by the presence of a con-
stellation of behavioral characteristics that accompany a Presentation of a new theory: Autoimmune
particular developmental course, with evidence of devel- mechanism of pathogenesis in autism
opmental delay within the first 3 years of life. Typically, Autism is a very complex disorder that may possibly re-
autism is characterized by “qualitative deficits” in 4 major sult from abnormal function of the neuroautoimmune
categories: (1) deficits of developmental rates and/or pro- (NAI) circuitry.1 More than 20 years ago, we hypothesized
files, (2) deficits of responses to sensory stimuli, (3) deficits that environmental factors such as a viral infection might
of speech, language, and communication capabilities, and cause autoimmunity to brain and thereby viral-immune
(4) deficits of social interactions and/or manners of relat- interactions may lead to pathologic changes in the brain of
ing to other people. Although the diagnosis of autism is children with autism.8-10 As outlined below, brain-specific
made during early childhood, the disorder continues to autoimmunity could be responsible for neuropathology in
persist well into adulthood, eventually becoming a lifelong autism.
neurodisability. Until about 10 years ago, the prevalence of Environmental Factors (virus) → Faulty
autism in America was 4 to 5 children per 10,000 births, but Immune Regulation → Autoimmunity to Brain →
the number of autism cases has increased dramatically.5,6 Neuropathology in Autism
The U.S. Centers for Disease Control and Prevention re- Several years ago, we hypothesized that a virus-
cently reported that as many as 1 in 125 to 150 children are induced autoimmune reaction to the developing brain,
diagnosed with autism—a rate that has increased at least in particular the developing myelin sheath, may cause
10 times in the last 10 years. Autism affects boys about 4 anatomic abnormalities of neural connections in the
times more often than girls, implying that the prevalence brains of children with autism.10 This is a very impor-
would be much higher in males, possibly reaching a rate tant event in the developing brain because the speed
of 1 in 84 boys. Furthermore, although the precise data of nerve-impulse transmission depends essentially on
are scarce, a similar trend of a sharp rise in rates of autism structural properties of the insulating myelin sheath,
spectrum disorders (ASD) has been described in other connecting nerve fibers, and axon diameter. We postu-
countries, for example, an estimated 200,000 children in lated that a virus-induced immune assault might cause
Canada, 1 to 2 million children in India, and 1.5 to 3 mil- “nicks” or subtle changes in the myelin sheath.2,4,10 An
lion children in China. autoimmune reaction to the developing myelin sheath
An estimated 10 or more genes have been impli- could ultimately lead to lifelong impairments of higher
cated in ASD,7 but their association is only indirect, brain functions, such as speech, language, communica-
and no single gene has been specifically identified for tion, and social interaction as well as other neurologic
autism. Based on this and other epidemiologic consid- symptoms that are commonly exhibited by children
erations, we had suggested that genetic factors would with autism.
Table 2
Serum level of antibodies to viruses in normal
and autistic children
Virus antibody (units) Measles Mumps Rubella HHV-6 CMV EBV
EA EBNA VCA
Normal children 3.3 ± 0.1 2.5 ± 0.2 3.2 ± 0.2 1.6 ± 0.6 0.28 ± 0.4 0.5 ± 0.04 1.2 ± 0.2 1.8 ± 0.3
(n = 32) (n = 30) (n = 45) (n = 37) (n = 30) (n = 44) (n = 44) (n = 44)
Autistic children 4.2 ± 0.1a 2.6 ± 0.3 3.3 ± 0.1 2.2 ± 5.3 0.23 ± 0.3 0.6 ± 0.04 0.9 ± 0.2 1.4 ± 0.2
(n = 87) (n = 32) (n = 74) (n = 45) (n = 30) (n = 44) (n = 44) (n = 44)
CMV: cytomegalovirus; EA: early antigen; EBNA: Epstein-Barr nuclear antigen; EBV: Epstein-Barr virus; HHV-6: human herpesvirus-6; VCA: viral capsid antigen.
a
Student t test was used to evaluate significance at a P value ≤ .05.
Table 4 Figure 3
Immunomonitoring of autoimmune markers Correlations between MMR antibodies and
in serum and CSF of autistic children MBP autoantibodies in autistic and normal
Patient code Blood (serum)a Brain (CSF)a children
1. Au063/063 + + – + – – 90
70 Autistic Autistic
3. Au407/408 + + – + – –
60
4. Au284/677 + + – + + –
50
5. Au705/706 + + – + + –
40
6. Au731/721 + + – + + –
30
7. Au739/740 + + – + – –
20
8. Au767/768 + + – + – –
10 Normal Normal Normal
9. Au769/770 + + + + – –
0
10. Au771/772 + + + + – – MMR MBP MMR/MBP
antibody autoantibody antibodies
Total (n = 10) 10+ 10+ 2+ 10+ 3+ 0
it was in normal children. Moreover, the detection of immunotoxicity is often demonstrated in cell cultures
human albumin antibodies by immunoblotting was of peripheral blood mononuclear cells in vitro. Conse-
mainly a negative result, and it was indistinguishable quently, a connection between vaccine-derived mer-
between autistic children and normal children.24 Thus, cury (thimerosal) and autism/ASD has been suggested,48
the elevated MMR antibodies in autistic children are albeit with a paucity of laboratory data. Although there
directed toward the measles subunit of the trivalent are several potential sources of mercury exposure,
vaccine and not against the human albumin, which as human exposure to mercury occurs primarily from vac-
stated, is used as a stabilizing protein in the MMR vac- cines because vaccinations or immunizations are man-
cine. Moreover, similar to measles virus alone, we found dated by the federal government.
a strong serologic correlation (>90%) between MMR Vaccines contain very small amounts of the chemi-
antibodies and MBP autoantibodies (Figure 3 ). cal thimerosal, which is used as a preservative; however,
Collectively, these findings suggested an etiologic the MMR vaccine does not contain this preservative,
link between the MMR vaccine and autoimmunity in according to the manufacturer. Relying on theoretical
autism. As far as we know, this is the first study of its grounds, it has been suggested that the mercury-induced
kind to examine associations between a viral factor neurotoxicologic changes in laboratory animals resem-
(virus serology) and an autoimmune factor (brain auto- ble neurodevelopmental delays in autistic children.48
antibodies) in a medical condition (autism/ASD) in However, this resemblance was not found when neu-
which autoimmunity appears to be the core of the prob- rologists carefully evaluated this hypothetical analogy.49
lem. Evidently, our study might also represent a novel While the controversy continued, we became interested
mechanism by which the so-called autistic regression in exploring if autoimmunity in autism could be caused
post-MMR vaccination might be explained in at least by exposure to mercury. Accordingly, we hypothesized
some children with ASD.22 that if autism involves a connection between mercury
In this respect, although more research must and autoimmunity, autistic children should harbor ele-
be done, we invoked the hypothesis that an atypical vated levels of mercury-induced autoimmune markers,
measles infection may be etiologically linked to brain namely antinucleolar antibodies (ANoA), anti-laminin
autoimmunity in autism. There is considerable cre- antibodies (anti-LA), and metallothionein antibodies
dence to this hypothesis based on studies of autoim- (anti-MT). In addition, we also studied serum levels of
munity-producing cytokines that have been reported metallothionein (MT) protein, a reliable marker of bio-
in the literature. First, autistic children have significant logical response to mercury and other heavy metals.
increases in autoimmunity-inducing cytokines such as We performed laboratory analyses of these markers
interleukin-12 (IL-12) and interferon-γ (IFN-γ) in favor in autistic children and normal children. The outcome
of a Th1 immune response.3,38 Second, the measles vac- of these laboratory studies was that the distribution of
cination with MMR vaccine mainly induces IFN-γ for a 3 autoimmune markers (ANoA, anti-LA, and anti-MT)
Th1 type of immune response. Since the MMR-induced and 1 biomarker (MT protein) did not significantly
immune response and autoimmune autism involve a change between autistic children and normal chil-
common immune cell (Th1), it is quite conceivable that dren.24,42,43 These were quite clear-cut results of labora-
MMR vaccine might also be involved in the pathogen- tory measurements of highly select markers of mercury
esis of autism.22,23 exposure. Therefore, based on our laboratory findings,
Taken together, these observations are directly we concluded that mercury is not a critical factor in caus-
related to the understanding of a basic mechanism of ing autoimmunity in autism.24,42,43 This negative finding,
autoimmunity in autism, but we believe more labora- however, does not entirely rule out the possibility that
tory research must be done to understand their precise mercury, if it is involved in autism, might trigger some
role in the pathogenesis of the disorder. other biochemical event, for example, mitochondrial
Heavy metal (mercury)–induced markers in oxidative stress and/or an inflammatory response.20
autism. The exposure to heavy metals, in particular Potential source of measles virus in autism. At pres-
mercury, is well known to cause immunotoxicity, auto- ent, the source of measles virus in autistic children is
immunity, and neurotoxicity in genetically predisposed not clearly defined. As stated above, the medical his-
laboratory animals. As cited elsewhere,42,43 heavy metal tory of children with an ASD does not show any record
Table 5
Similarities between measles infection and autism
Measles virus (MV) Autism
1. M
V infects brain regions: temporal and frontal lobes of the 1. Affected brain regions: temporal and frontal lobes of the
cerebral cortex, cerebellum, hippocampus, amygdala, cerebral cortex, cerebellum, hippocampus, amygdala,
cingulated gyrus, and hypothalamus.50 cingulated gyrus, and hypothalamus.51
2. M
V causes immunosuppression, specifically of T helper 2. Autistic children have immunosuppression,
(CD4+) cell function.52,53 particularly T helper (CD4+) cell function.32,36,37
3. M
V (MMR-HA) stimulates antigen-presenting cells 3. Autistic children have elevated levels of IFN-γ
to produce IFN-γ for Th1 cellular immune response.54,55 and IL-12 for Th1 cellular immune response.3,38
4. M
V causes immune activation to produce elevated levels of 4. Autistic children have immune activation as shown
sCD8 antigen.56 by elevated level of sCD8 antigen.9
5. MV infection is treated with vitamin A.57,58 5. Autistic children respond to vitamin A-containing cod
liver oil.59
involved, and 7% said there was no vaccine connection We took the first approach because it represents
with symptoms of their children. a physiologic state in the body, and so we measured
It is of considerable etiologic significance that serum levels of cytokines in autistic children. We
autism was prevalent among children who received the found that the serum level of only 3 cytokines (IL-2,
MMR vaccine. According to these parents, their chil- IL-12, and IFN-γ) was significantly elevated in autis-
dren were born normal and were developing normally, tic children38 but the serum levels of 6 other cytokines
but there was a sharp regression or developmental (IL-1, IL-4, IL-6, IL-10, IFN-α, and TNF-α did not sig-
delay shortly after the administration of MMR vaccine. nificantly differ between normal children and autistic
Although these reports are nonscientific and unaccept- children.3,9,38 Because of a specific increase of IL-12 and
able on scientific grounds, they certainly prompted us IFN-γ, we were the first to suggest that autism involves
to examine vaccines and autism through laboratory the Th1 type of immune response.38 Subsequently, we
research. Thus, we conducted laboratory studies of virus conducted a study of IL-2, IL-6, and TNF production
and vaccine serology and brain autoantibodies in chil- by PBMNCs.
dren with autism. We found that IL-2 production was significantly
As described here, there is a clear-cut serologic asso- increased in autistic children. The production of IL-6
ciation between the MMR-derived measles strain and and TNF by PBMNCs of autistic children was moder-
autism. Although more experimental research is needed ately higher in autistic children than in normal children,
to confirm this link, we also noted certain important but the difference did not attain statistical significance.3
similarities of manifestations between measles infection Our result of TNF production in autistic children is con-
and autism/ASD (Table 5). Measles infects brain regions sistent with a previous report.32 Recently, 2 other groups
such as the temporal and frontal lobes, hippocampus, of researchers took alternative approaches and found
and amygdala,50 which are also affected in the brains of that PBMNCs of autistic children produce elevated lev-
autistic children.51 Measles virus is well known to induce els of IL-12 and IFN-γ or express higher than normal lev-
immunosuppression of T helper cells,52,53 whose func- els of messenger RNA for IFN-γ (see Singh 20033). Taken
tion is also reduced in children with autism.32,34,36,37 The together, these findings demonstrate the existence of
MMR vaccine elicits cellular immunity via Th1 cells54,55; the Th1 type of immune response in autistic children,3
the same type of cell is also involved in autism.3,38 Measles which would also be consistent with autoimmune
virus causes immune activation as reflected by elevated pathology in autism38 because the IL-2, IL-12, and IFN-γ
levels of soluble CD8 antigen,56 which is also elevated cytokines are well-known inducers of autoimmune dis-
in autistic children.9 Furthermore, vitamin A treatment eases.60,61
has been used for both measles infection57,58 and autistic Regarding the pathogenesis of immune-mediated
children.59 This resemblance between measles infection diseases, immune activation is one of the primary events
and autism, together with our findings of elevated mea- in autoimmunity, inflammation, and viral infections.
sles serology and abnormal measles antibody response, Immune activation leads to spontaneous proliferation of
might point to an etiologic link of measles virus in AAD, PBMNCs, increased expression of activation markers on
as described here. PBMNCs, and increased accumulation of blood mono-
nuclear cell-derived soluble antigens, mainly cytokines,
Cytokine studies in autism cytokine receptors, and adhesion molecules.
Several years ago, we studied cytokine regulation in Based on these considerations, immune activation
autism.3,9,38 Cytokine studies can be performed by 3 occurs naturally in autistic children because they have
different approaches: (1) cytokines can be measured elevated levels of immune-activation antigens such as
in biological fluids such as serum, plasma, or cerebro- soluble CD8, IL-2, IL-12, and IFN-γ 9,38 and their blood
spinal fluid, which represent endogenously (or in vivo) contains activated T cells.35,36 Thus, it is reasonable to
produced circulating cytokines, (2) cytokine production conclude that the increase of IL-12 in autistic children
can be studied by peripheral blood mononuclear cells points to antigenic stimulation of Th1 cells that, via
(PBMNCs) after mitogen stimulation in vitro, and (3) INF-γ, may induce autoimmunity.3,38 The IL-12 cytokine
cytokine-specific mRNA expression can be measured in selectively promotes the development of Th1 cells,60
PBMNCs after mitogen stimulation. and Th1 cells initiate the pathogenesis of organ-specific
autoimmune diseases.61 Immune activation is also well of antibodies to viruses such as measles virus, mumps
known to exist in autistic children because they harbor virus, rubella virus, CMV, or HHV-6. We have shown that
elevated levels of acute-phase reactants, including C- the level of measles antibody is elevated in many autis-
reactive protein (CRP) and S-100 protein,20 that have tic children, which could be a sign of a present infec-
also been linked to autoimmune diseases.62 tion, a past infection, or an immune reaction to MMR
vaccine.2,22,23
Testing for autoimmunity in autism Vaccine serology profile. This test detects antibod-
Deriving from neuroimmunologic research,1 autoim- ies to vaccines, including MMR and DPT. We showed
munity has been shown to play a key role in the patho- that a significant number of autistic children, but not
genesis of neurologic disorders.9,10 The list of these dis- normal children, harbor a unique type of measles anti-
orders now also includes autism.2-4 Since the brain is body to MMR vaccine. This antibody might represent an
the affected organ, the autoimmune response will be abnormal or inappropriate immune reaction to this vac-
directed toward the brain. cine and should be tested in relation to autoimmunity
Autoimmunity is commonly characterized by the in autism.2,22
expression of certain autoimmune factors. These factors Cytokine profile. Two cytokines, IL-12 and IFN-γ,
are important for identifying a brain-specific autoim- play a very important pathogenic role in autoimmune
mune response, which we have identified in children diseases in that they initiate an autoimmune reaction via
with autism. By performing blood tests, we can deter- induction of the Th1 type of white blood cells. We have
mine if a patient shows autoimmunity to brain, if he or found that these 2 cytokines are selectively elevated in
she is a candidate for experimental immunomodulation autistic children, suggesting the induction of autoim-
therapy, and if the response to therapy is effective. Thus, munity via Th1 cells in autism. Therefore, they should be
this type of immune evaluation is extremely important measured as a sign of impaired cellular autoimmunity
in helping patients with autism. The specific tests are in patients with autism.3,9,38
listed below. Serotonin profile. This test measures the serum or
Immune panel profile. It is strongly recommended plasma level of serotonin. We have found that patients
that all children with autism/ASD be tested for a basic with autism have abnormal levels of serotonin, which
immune panel profile. This panel includes testing them should be tested before administering treatment with
for serum immunoglobulins; a complete blood count selective serotonin reuptake inhibitor (SSRI) therapy.
for mononuclear cells (lymphocytes and monocytes); Elevated serotonin levels in autism might also be related
blood enumeration of T cells, B cells, NK cells, and T- to autoimmune reaction to serotonin receptors in the
cell subsets (helper T cells and suppressor T cells). For brain.19
research purposes, it is also important to evaluate lym- Mercury-induced autoimmune markers. This test
phocyte function, for example, mitogen-stimulated lym- assays for autoimmune reaction to mercury (or heavy
phocyte proliferation and NK cell activity. All of these metal) exposure. These markers include: (1) antinuclear
immune parameters have been found to be abnormal in antibodies against nucleolar antigens (ANoA), (2) anti-
children with autism/ASD (see Table 1 and Singh4). laminin antibodies (ALA) against basement-membrane
Brain autoantibody profile. This test detects anti- proteins, and (3) antibodies to metallothionein pro-
bodies to 2 brain proteins—the MBP and the NAFP. We tein (anti-MT). In addition, the serum level of MT pro-
have found that the incidence of MBP autoantibody in tein should also be measured as an index of biological
the autistic population is markedly higher than that of response to exposure to heavy metal or mercury. We
the normal population; hence, it serves as a primary have found that only a very small number of autistic
marker of the autoimmune reaction in autism. In con- children are positive for these antibodies and MT pro-
trast, the incidence of NAFP antibody in autistic patients tein, but their levels did not differ significantly from nor-
is only marginally higher than that of normal controls, mal children.42,43
making it a secondary marker of choice. It is, however, Acute-phase reaction (APR) markers. This test should
recommended that these 2 autoimmune markers be be done to assess acute-phase reaction (APR), which is an
tested simultaneously.2,10,17,18 excellent sign of inflammation. The test includes mea-
Virus serology profile. This test measures the level surement of certain biomarkers, chiefly C-reactive protein
(CRP) and S100 protein. We recently found significantly developed beverage formulation of TF called RioVida
higher than normal levels of these 2 markers, suggesting (4Life Research, Inc.). To that end, however, the dose of
the existence of APR in autistic children.20 TF should be increased to 1200 to 1800 mg TF per day
instead of the recommended daily dose.
Immunomodulation therapy (IMT) in autism As recorded by parents, we observed noticeable
Several lines of laboratory findings have demonstrated improvement in areas of language, speech, social inter-
the role of autoimmunity in the pathogenesis of autism. action, sleep, attention span, and cognitive behaviors,
The idea that autism is an autoimmune disorder is also plus overall better physical health, perhaps due to
strengthened by the fact that autistic patients respond reduced infections.41 Furthermore, the improvement
well to treatment with immunomodulating agents.2-4 in autistic characteristics was also reflected by consid-
Immune intervention can produce immunomodula- erable lowering of the Autism Treatment Evaluation
tion—a state of balance between immunosuppression Checklist (ATEC) score (Autism Research Institute, San
and immunostimulation. Since autistic patients do not Diego, CA, USA). Although these findings are prelimi-
show a classical primary immunodeficiency, simply nary, we think that a properly designed large-scale trial
boosting their immunity is not a good strategy. They would be an important step in the right direction to help
do, however, have immune abnormalities. Therefore, children with autism/ASD with TF-induced immuno-
depending on the nature of the immune abnormality, therapy.41
the goal of immunomodulation therapy (IMT) should Immunoglobulin therapy. This approach to treat-
be to achieve immune balance by normalizing or recon- ment is already in practice to help autistic children with
stituting immune functions. This will allow a more bal- autoimmune abnormalities. Open-label trials of intra-
anced immune response, avoiding major fluctuations venous immunoglobulin (IV-IG) have shown that most,
of overt immune activity, which could be detrimental but not all, autistic children respond favorably to this
to the patient. IMT should always be given in consulta- treatment.32 Clinically, children so treated have shown
tion with a physician, preferably a clinical immunolo- improvements in language, communication, social
gist, allergist, or hematologist. The following is a partial interaction, and attention span.
list of IMTs that should be considered for patients with Several years ago, we suggested the use of “oral-
autism. IG” as an alternative approach to IV-IG. In a subjective
Transfer factor therapy. Transfer factor (TF) is study, oral-IG showed significant improvement of autis-
an immunomodulator for regulating cellular immune tic characteristics in patients with autism/ASD, and the
functions of NK cells and T lymphocytes, especially outcome appeared to be about the same as or some-
during viral and microbial infections. To be effective, what better than IV-IG.40 Further studies are needed to
TF—commonly known as dialyzable leukocyte extract establish the efficacy of this modality.
(DLE)—is normally made from the leukocytes of highly Autoantigen therapy. Patients with autoimmune
select blood donors. By using DLE-TF, open-label stud- diseases are also treated with oral administration of
ies have shown symptomatic improvement of some autoantigens. This is also applicable to autism. Since
autistic children.8,39 Unfortunately, DLE-TF is extremely MBP is the autoantigen in autism, autistic patients
difficult to prepare, and there are batch-to-batch varia- have responded positively to nutritional supplements
tions, among other problems inherently associated with containing brain MBP or brain myelin, for example,
the preparation of this particular form of TF. However, Sphingolin.2
there is now a commercial brand of TF (4Life Research, Glutathione therapy. Glutathione is a natural
Inc.) that targets NK cells in particular, and that also immunomodulator, antioxidant, and detoxifier. Owing
brings about overall immunomodulation through T to these biological functions, glutathione is commonly
lymphocytes in the body. regarded as the body’s most potent protector against
Autistic children are well known to have faulty immu- infections, autoimmune problems, and other abnor-
nomodulation, including reduced numbers and function malities, including oxidative stress.63 Early results show
of NK cells, which makes these children good candidates signs of some improvement in autistic children.
for TF therapy. In our case studies,41 we recently found Glyconutrient therapy. Recently, glycobiology
that autistic children respond favorably to a scientifically research has identified certain glyconutrients that con-
tain specialized carbohydrates. One such glyconutrient is did not support the idea that thimerosal-derived mer-
Ambrotose (Mannatech, Inc., Coppell, TX, USA). Although cury induces autoimmunity in autism. The existence
scientific evidence is lacking, Ambrotose-containing prod- of autoimmune problems in autistic patients and their
ucts have been claimed to improve some behavior in autis- responsiveness to treatment with IMT also supports an
tic children (see www.mannatech.com). etiopathogenic role of virus-induced autoimmunity in
Steroid therapy. Steroids such as prednisone and/or autism.
adrenocorticotropic hormone (ACTH) are commonly Considering that autism affects an estimated 2 to 2.5
used as the first course of treatment for patients with million Americans, if 75% of these individuals have AAD
autoimmune diseases. Although clinical trials of ste- or autoimmunity, a very significant number (1.5 to 1.9 mil-
roids in autistic patients have not been performed, there lion) could benefit directly from autoimmunity research. If
are some reports showing benefits and improvement the world population of persons with autism/ASD is taken
of behavioral characteristics in patients with autism/ into account, the impact of autoimmunity research could
ASD.64 However, the individual case history of viral be much greater, impacting the lives of millions more
infection should be taken into account before adminis- worldwide.
tering steroid treatment because viruses can sometimes Therefore, the author of this review article suggests
exert immunosuppressive effects. that autism be considered on medical grounds as an auto-
Plasmapheresis therapy. Plasmapheresis or plasma immune disorder, which in turn would draw much wider
exchange (PE) therapy is often used to help patients with international attention of medical doctors and biomedi-
infections, autoimmune diseases, and immune complex cal researchers. After all, the clinical presentation of auto-
diseases. PE therapy has been successfully used to improve immunity is a medical condition and, likewise, autism
clinical symptoms in patients with a wide variety of neu- should also be regarded as a medical condition. In this
rologic disorders, including CNS dysmyelination65 and respect, autism may very well be a psychiatric condition
obsessive-compulsive disorder.66 Because autism involves that defines the academic role of psychoneuroimmunol-
viral infection and CNS-myelin autoimmunity, we were ogy (PNI) or immunopsychiatry in the clinical practice of
the first to suggest that this treatment modality be explored psychiatry. Naturally, this topic offers a novel direction of
in patients with autism.2-4 future research for helping persons diagnosed with autism
and related neurobehavioral disorders.
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2005;3-4:117-125. merosal-containing vaccines. J Biomed Sci 2004;11:607- exchange for severe attacks of CNS dysmyelination: predic-
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1998;89:105-108. children having exposure to vaccine-derived thimerosal. through discoveries in natural treatments. Royal Palm
22. Singh VK, Lin XE, Newell E, et al. Abnormal measles- Pediatr Allergy Immunol. 2006;17:291-296. Beach, FL, USA: Association for Comprehensive Neuro
mumps-rubella antibodies and CNS autoimmunity in chil- 44. Uhlmann V, Martin CM, Scheils O, et al. Potential viral Therapy; 2005:163-168.
dren with autism. J Biomed Sci. 2002;461:359-364. pathogenic mechanism for a new variant inflammatory 67. Singh VK. Autoimmune pathogenesis of autism: pro-
23. Singh VK, Jensen R. Elevated levels of measles antibod- bowel disease. J Clin Pathol. 2002;55:84-90. filing an autoimmune subset. Invited presentation at: Third
ies in children with autism. Pediatr Neurol. 2003;28:292- 45. Wakefield AJ, Stott C, Lamb K. Gastrointestinal co- International Medical Convention—Autism Medical Con-
294. morbidity, autistic regression and measles-containing vac- ference, sponsored by Autisme et troubles envahissants du
24. Singh VK. Autism, vaccines, and immune reactions. cines, positive, re-challenge and biological gradient. Medi- developpement Montreal (ATEDM); May 3-4, 2002; Mon-
Presented at: Institute of Medicine (IOM) Conference, Na- cal Veritas. 2006;3:796-802. treal, Quebec, Canada.