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autism, Vaccines, and immune reactions
Vijendra K. Singh, Ph.D.
Research Associate Professor of Neuroimmunology
Department of Biology, Center for Integrated Biosystems
Utah State University
Autism is the fastest-growing developmental disability in children today.
Millions are affected worldwide, and the numbers are rising sharply to
epidemic levels. Autism causes neurological and behavioral deficits in
children, impairing their ability for social interaction, language,
communication, cognition, and imagination. Autism is an idiopathic
disorder of unknown etiology. Current theories include genetic factors,
immune factors, viral factors, neural factors, and yet other unidentified
factors. For last 10-12 years, I focused on autoimmune mechanism of
pathogenesis and autoimmune therapy for patients affected with the
disorder. I started out working on autism with the idea of “Autism as an
Autoimmune Disorder” and my hope was to use autoimmunity as a target of
drug development for treating autism [1-3]. Indeed, this is happening
today [4-6]. In my presentation today, I will be speaking on the topic of
“autism, vaccines, and immune reactions” and to examine the possibility of
a causal link between vaccines and autism.
I view autism as a very complex disorder with different subsets and one
such subset might be autoimmune in origin. I have studied autism as an
autoimmune disorder, in which viral-autoimmune interplay may lead to
pathological changes in the central nervous system (CNS). The essence of
my “Autoimmune Hypothesis” is that a virus-induced autoimmune response to
developing brain myelin may impair anatomical development of neural
pathways in autistic children [3,4]. This line of thinking relies on the
fact that the speed of nerve-impulse transmission depends essentially on
structural properties of the insulating myelin sheath, connecting nerve
fibers, and axon diameter. The anatomical changes could ultimately lead to
life-long disturbances of higher mental functions such as learning, memory,
communication, social interaction, etc. Fundamentally, therefore, I think
that autism can be treated successfully using some of the therapies proven
effective in treating other autoimmune diseases. To that end, however, the
complete identification and characterization of autoimmune pathology in
autism is of utmost importance today.
Environmental Factors (viruses/vaccines) à
Autoimmunity to Brain
2. Viruses as causal factors in autism:
Measles is likely an etiological agent.
Leading scientists in the field commonly believe that the viral infections
trigger autoimmune responses and eventually lead to organ-specific
autoimmune diseases. In autism, the trigger mechanism is not known but
viral infections have been suspected.
Viruses can enter the brain through the nasopharyngeal membranes or induce
an autoimmune response against the brain, thereby impact the development
of the central nervous system (CNS). Since the onset of the disorder is
quite early on in life, viruses might serve as teratogens (agents that
cause developmental malfunctions) etiologically linked to autism. Children
with congenital rubella had certain autistic-like behaviors. Some autistic
children did not make antibodies to rubella vaccine even after the
repeated rubella immunization. Few cases of autism have also been
described among children with congenital cytomegalovirus (CMV) infection.
Recently, we took a
novel approach of studying viral etiology in autism [7-9]. We raised two
simple questions: First, do autistic children harbor abnormal virus
serology (antibody levels) and, secondly, is there a correlation between
virus serology and brain antibodies. We studied immune response to viruses
by measuring the level of their antibodies. For this purpose, we measured
antibodies to five viruses: Measles virus, mumps virus, rubella virus, CMV,
and human herpesvirus-6 (HHV-6). To our surprise, we found that the
antibody level of only the measles virus, but not of the other viruses
tested, was significantly higher in autistic children than the normal
children [reference #4 and #9; Table 1 and Fig. 1]. In addition, we found
an interesting correlation between measles antibody and brain autoimmunity,
which was marked by myelin basic protein (MBP) antibodies. These two
immune markers correlated in 90% or greater autistic children, suggesting
a causal link of measles virus with autoimmunity in autism. But the
serology to other viruses and other brain autoantibodies did not show this
correlation. This was a very important finding that prompted us to
postulate a temporal link of measles virus in the etiology of the disorder
[Singh et al., 1998; reference #7]. To that end, it is also noteworthy
that the immune manifestations of measles virus infection are quite
similar to the immune abnormalities in autistic children, indirectly
pointing to an etiological link of measles infection in autism.
Table 1. Viral antibodies in the sera of autistic children
CMV-IgG Autistic (n=30) 0.23 ±
0.28 ± 0.46
HHV-6-IgG Autistic (n=45) 2.18 ±
Rubella-IgG Autistic (n=31) 3.59 ±
2.90 ± 0.81
Mumps-IgG Autistic (n=30) 2.57 ±
2.46 ± 1.31
Measles-IgG Autistic (n=42) 3.83 ±
Normal (n=26) 3.08 ±
Viral antibody levels are shown for measles virus, mumps virus and rubella
virus in autistic children (n=87, dotted bars), normal children (n=32,
solid bars) and siblings of autistic children (n=14, shaded bars).
Note: As evaluated by the Student’s t test, the
measles antibody level was significantly (p≤0.05) increased in
3. Vaccines as risk factors in autism:
MMR could potentially cause autism via an
Although there is very little experimental data, parents of autistic
children commonly report the onset of autistic characteristics shortly
after immunization with measles-mumps-rubella (MMR) and/or
diphtheria-pertussis-tetanus (DPT) vaccines. This subset is sometimes
referred to as “Autistic Regression.” This population includes
approximately 85% of autistic children quite commonly with a new diagnosis
of the disorder. The remainder 15% of children either does not have any
history of adverse vaccine reaction or they have diagnosis of autism
without the vaccines. This information, albeit anecdotal, was quite
important when we expanded our investigation further by using the MMR
vaccine (see below).
To examine vaccines as risk factors in autism, we conducted a study of
serology (antibody levels) to three vaccines: MMR, DPT and DT (diphtheria-tetanus).
Once again, we raised the same two questions: First, do autistic children
harbor abnormal vaccine serology (antibody levels) and, secondly, is there
a correlation between vaccine serology and brain autoantibodies. Through
our experimental research , we found that the level of MMR antibodies
was significantly higher in autistic children as compared to normal
children or other disease children [Fig. 2]. Moreover, it is noteworthy
that autistic children exhibited a very high degree of specificity for MMR
antibodies, similar to our previous finding for measles antibodies, which
is of paramount importance in establishing an etiological role of MMR in
autism. Furthermore, we characterized that this abnormal MMR serology was
due to antibodies to measles subunit but not the mumps or rubella subunit
of the trivalent vaccine MMR . The same result was also found when we
used monovalent measles vaccine in lieu of the trivalent MMR vaccine,
furthermore pointing to a problem of only the measles subunit . Once
again, there was a positive correlation (90% or greater) between MMR
antibody and MBP autoantibody [Fig. 3; reference #8]. These findings led
me to speculate that the measles subunit of the MMR vaccine might trigger
an autoimmune reaction in a significant number of autistic children [7-9].
While more research is necessary, I think this is an excellent working
hypothesis to explain autoimmune subset of autism and it may also help us
understand why some children show “autistic regression” after MMR
immunization. To that end, it is also important to note that the MMR
vaccine induces a Th-1 cellular response , an immune response that is
also found in autistic children [6,11].
MMR antibodies in autism. At four serum dilutions, the MMR antibody
levels are shown for autistic children (n=24, solid circles), normal
children (n=14, solid squares), and other disease children (n=16,
solid triangles). Note: MMR antibody level
was significantly (p≤0.05) increased in autistic children.
MMR and MBP antibodies in autistic children. Note that 90% or
more correlation was found between MMR and MBP antibodies in
autistic children (vertical bars) but not in controls that
included normal children (baseline box 1), normal siblings (baseline
box 2), and other disease children (baseline box 3).
4. Immune reactions in autism:
Autoimmunity is the core of the problem.
Several groups have demonstrated abnormal immune reactions,
in particular autoimmunity, in children with autism and related spectrum
disorders. Autoimmunity is an abnormal immune reaction in which the immune
system goes haywire and reacts abnormally against body’s own organs, and
the end result is an autoimmune disease. Several factors contribute to
autoimmune diseases. Microbes such as viruses can trigger autoimmune
diseases. They are generally linked to certain genes that control immune
responses. They cause immune abnormalities of white blood cells (WBC), in
particular that of T cells, B cells and NK cells. They induce the
production of pathogenic antibodies, especially the organ-specific
autoantibodies. They involve hormonal factors. And they generally show a
gender preference. This is also the case with autism, which means that
several autoimmune factors have also been found in autistic children [for
various citations see references 1-9].
Some of the important
autoimmune factors in autism are:
Autism is commonly
associated with microbial infections, in particular viral infections.
have immune abnormalities, especially those that characterize an
autoimmune reaction in a disease.
inappropriate immune responses to vaccines, in particular MMR.
increased frequency for immune response genes (e.g., HLA, C4B null
allele or extended haplotypes) that render susceptibility to autoimmune
Autism involves a
gender factor as it affects males about four times more than females.
Autism has a
family history of autoimmune diseases such as multiple sclerosis,
rheumatoid arthritis, and diabetes.
involves a hormonal factor, for example secretin and endorphins.
respond well to immune modulation therapy (IMT).
5. Mercury and autism:
Mercury is not related to autoimmunity.
Because both autism and mercury exposure involve autoimmunity, mercury has
recently been proposed as an environmental risk factor in
autism. However, the laboratory analysis showed that the blood levels of
mercury do not rise above safe levels in infants and children receiving
thimerosal-containing vaccines . We hypothesized that if autism
involved a connection between mercury exposure and autoimmunity then
autistic children should harbor elevated levels of mercury-induced
autoimmune markers, namely the antinucleolar antibodies and antilaminin
antibodies. So, we recently conducted a pilot study of these two
autoimmune markers in autistic children and normal children. The results
of our experimental study, for the first time, showed that the
distribution of these two markers did not change in autistic children.
Quite plainly, mercury is not a risk factor for autoimmunity in autism [Our
research in progress].
Immune Modulation Therapy (IMT) in Autism
Accumulating evidence suggest that autoimmunity plays a key role in the
pathogenesis of autism. The idea that autism is an autoimmune disorder is
further strengthened by the fact that autistic patients respond well to
treatment with immune modulating drugs [4-6]. Immune interventions can
produce immune modulation – a state of suppression or stimulation. Since
autistic patients do not show a classical primary immunodeficiency, simply
boosting their immunity is not a good strategy. However, they do have
immune abnormalities and therefore, depending on the nature of the immune
abnormality, the goal of IMT should be to normalize or reconstitute the
immune function. This will permit a more balanced immune response,
avoiding major fluctuations of overt immune activity that could be
detrimental to the patient. The IMT should always be given in consultation
with a physician, preferably a clinical immunologist, allergist or
hematologist. For autism, the recommended list of IMT includes steroid
therapy, immunoglobulin therapy, oral autoantigen therapy, transfer factor
therapy, immunomodulating drugs, and plasmapheresis.
Summary and concluding remarks
Considering an estimated
population of 500,000 Americans with autism (not including all spectrum
disorders), I think that between 250,000 to 350,000 autistic patients
could benefit directly from autoimmunity research today.
The current genetic research
estimates that no more than 10% of all autistic cases are genetic in
origin. Simply put, the remainder 90% of autistic cases is sporadic with a
non-genetic etiology. I tend to think that the sporadic form is by and
large an “acquired” subset involving autoimmunity. This subset is likely
triggered by a virus, possibly measles virus or MMR vaccine. I recently
designated this subset as an “Autoimmune Autistic Disorder (AAD)” – a term
coined to describe autoimmune subset of autism (Singh VK: May 1, 2003). I
think that the autoimmunity research has a global impact for treating
autism worldwide hence the physicians and researchers should pay a closer
attention to autoimmunity research in autism.
Based upon our experimental
research, it is plausible to postulate that an atypical measles infection
that does not produce a typical measles rash but manifests neurological
symptoms might be etiologically linked to autoimmunity in autism. The
source of measles virus could potentially be MMR vaccine or a mutant
measles strain, but more research is necessary to establish either of
these two possibilities.
Fundamentally, I tend to think
that autistic children have a problem of their immune system, which is the
“faulty immune regulation.” Hence they have abnormal immune reactions to
measles virus and/or MMR vaccine.
I am a strong advocate of
immunization program worldwide, chiefly because the vaccines are the best
preventive measures against deadly infections available to mankind today.
So, I am not an anti-vaccine person. I do believe however that the safety
of vaccines must be as absolute as humanly possible because they are
administered into healthy children, adults and elderly.
since everything changes with time, I firmly believe that it is time to
re-evaluate the safety of vaccines and the manner in which we practice
immunizations. Vaccines are well known to cause numerous adverse reactions
in humans and no matter how rare they might be it is time to pay a closer
attention to them. I don’t think the epidemiological studies will suffice
the purpose but the laboratory-based experimental research is urgently
needed. We need new policies simply because the existing policies are not
in line with our modern knowledge of human immunology, virology, and
genomics. This is clearly exemplified by our experimental approach
involving laboratory techniques that did not exist 30-40 years ago when
the vaccines were originally developed. Indeed, there is persuasive
evidence to suggest that the MMR vaccine could potentially cause autism or
a regressive form thereof in a significant number of children. At this
juncture, I would also like to recommend a new policy of “Testing
immunity before vaccination or immunization” that should help identify
immunocompromised children who otherwise might react adversely to vaccines.
The cost should not deter us from implementing this policy especially when
the lives of hundreds and thousands of children and their families are
Brain, Autoimmunity and autism. Invited presentation at the Annual
Conference of the Long Beach Chapter of Autism Society of America (ASA),
Long Beach, California; October 13-14, 1995.
Immunodiagnosis and immunotherapy in autistic children. Presented at
the International Congress of Neuroimmunology, Philadelphia,
Pennsylvania; Sept. 8-11, 1987.
et al. Antibodies to myelin basic protein in children with autistic
disorder. Brain Behavior and Immunity 7: 97-103 (1997).
Neuro-immunopathogenesis in autism. In: NeuroImmune Biology:
New Foundation of Biology, Vol. 1: 443-454 (2001).
Immunotherapy for brain disease and mental illnesses. Progress in
Drug Research 48: 129-146 (1997).
Cytokine regulation in autism. In: Cytokines and Mental Health,
Edited by Z. Kronfol (2003) pp. 369-383, Kluwer Acad. Publishers,
et al. Serological association of measles virus and human
herpesvirus-6 with brain autoantibodies in autism. Clin. Immunol.
Immunopathol. 89: 105-108 (1998).
Abnormal measles-mumps-rubella antibodies and autoimmunity in children
with autism. Journal of Biomedical Science 9: 359-364 (2002).
Elevated levels of measles antibodies in children with autism.
Pediatric Neurology 28: 292-294 (2003).
et al. Kinetics of immunologic responses after primary MMR
vaccination. Vaccine 15: 10-14 (1997).
Plasma increase ofinterleukin-12 and interferon-gamma: Pathological
significance in autism. Journal of Neuroimmunology 66: 143-145
Mercury concentrations and metabolism in infants receiving vaccines
containing thiomersal: a descriptive study. Lancet 360: 1737-1741