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MEDICINE
Autoimmune Diseases
A Rising Epidemic
Yoo Jung Kim ‘14
Image retrieved from http://pharmrev.aspetjournals.org/content/59/4/289/F13.large.jpg
(Accessed 8 May 2011).
German hematologist and immunologist Paul
Ehrlich, the 1908 Nobel Laureate of Medicine.
His theory against the possibility of autoimmune
response remained influential for over 50 years.
I
n the dawn of the twentieth century, Paul Ehrlich, an illustrious
German hematologist, immunologist, and 1908 Nobel Laureate of Medicine, posited a biological theory of horror autotoxicus, the unwillingness of
the organism to endanger itself by the
formation of toxic autoantibodies. In
other words, an organism’s immune
system could not develop an autoimmune response. Ehrlich’s theory would
remain as a widely accepted canon in
the then fledgling field of immunology,
despite ample evidence to the contrary
published by his scientific contemporaries and later biologists. Their
findings suggested that autoimmune
reactions are responsible for a wide
range of disorders, including paroxysmal cold hemoglobinuria, sympathetic
ophthalmia, ocular inflammation due
to lens antigens, some hemolytic anemias, and certain encephalitides. (1)
Ehrlich’s postulation would linger
on for more than five decades, until it
was finally debunked by a discovery
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made by a young scientist named Noel
Rose, now the Director of the Johns
Hopkins Autoimmune Disease Research Center. Working as a part-time
research assistant in the 1950s, Rose
injected thyroglobulin, a major protein
constituent of the thyroid gland, back
into the thyroids of the rabbits from
which it was originally derived, and noticed that the rabbits soon developed
lesions in their thyroid tissue—a sign
deduced to be an autoimmune response
similar to that of a known condition
called Hashimoto’s Thyroiditis (3). Yet,
despite Rose’s discovery, over a decade
passed before autoimmunity became a
commonly accepted precept; the damage was done. The time it took the scientific community to fully accept the
growing reality of autoimmunity has
delayed the translation of its findings
into medical knowledge, with grave
implications in current epidemiological diagnosis of autoimmune diseases.
The Immune System and
Autoimmunity
An immune system is a highly
regulated biological mechanism that
identifies and reacts to antigens from
various foreign substances found in
an organism’s body and reacts to these
possible pathological threats by producing certain types of lymphocytes
such as white blood cells and antibodies that have the ability to destroy or
neutralize various germs, poisons and
other foreign agents (2). Typically, the
immune system is able to distinguish
the foreign agents from the organism’s
own healthy cells and tissues. Autoimmunity, on the other hand, describes a
diseased condition in which an organism fails to recognize its own cells and
tissues, thereby enabling the immune
system to trigger a response against its
own components. (2). A low degree of
autoimmunity is an integral part of an
effective immune system. For example, low-level autoimmunity has been
demonstrated to be a possible factor in
reducing incidence of cancer through
versatile CD8+ T cells, which kill target
self-cells by releasing cytokines capable
of increasing the susceptibility of target cells to cytotoxicity, or by secreting
chemokines that attract other immune
cells to the site of autoimmunity (8).
Autoimmune Diseases
Autoimmune diseases occur when
there is interruption of the usual control
process, thereby allowing the system to
malfunction and attack healthy cells
and tissues (9). A common example of
autoimmune disease is Type I Diabetes,
which affects nearly a million people in
the United States. It is a condition in
which the pancreas does not produce
enough insulin to control sugar blood
levels due to the autoimmune destruction of the insulin-producing pancreatic β cells (10). Some other common
autoimmune disorders include rheumatoid arthritis, systemic lupus erythematosus (lupus), and vasculitis (9).
Autoimmune disorders typically
fall into two categories: systematic
and local. Systemic autoimmune diseases are associated with autoantibodies, which are not tissue specific,
and the spectrum of damage may affect a wide range of tissues, organs,
and cells of the body. Localized autoimmune diseases are associated with
organ-specific conditions that affect
a single organ or tissue. However, the
boundary between systematic and nonsystematic disorders becomes blurred
during the course of the disease as the
effect and scope of localized autoimmune disorders frequently extend beyond the initially targeted areas (6).
The onset of autoimmune disease
is associated with a trigger, which can
be pulled in numerous ways. In one
possible example, certain substance
in the body that is normally confined
to a specific area may be released into
another area due to internal trauma;
the translocation may stimulate the
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immune system to recognize a natural
body component as foreign and trigger an autoimmune response. In another scenario, a normal component
of the body may be altered via virus, a
drug, sunlight or radiation; the altered
substance may then appear foreign to
the immune system. Very rarely, a foreign substance resembling a natural
body component may enter the body,
thereby inducing the immune system
to target both the similar body substance and the foreign substance (11).
Just as the triggers for autoimmune disorders are wide and varied, so
are their effects. The debilitating effects
of various autoimmune disorders include the destruction of a specific type of
cell or tissue, stimulation into excessive
growth, or interference in function. Organs and tissues affected by more common autoimmune disorders include
components of the endocrine system,
such as thyroid, pancreas, and adrenal
glands; components of the blood, such
as red blood cells; and the connective
tissues, skin, muscles, and joints (9).
Treatments for
Autoimmune Diseases
Since cures are currently unavailable for most autoimmune disorders,
patients often face a lifetime of debilitating symptoms, loss of organ and tissue function, and high medical costs
(5). For many autoimmune disorders,
the goals of treatments are to reduce
chronic symptoms and lower the level
of immune system activity while maintaining the immune system’s ability to
fight foreign contaminants. Treatments
vary widely and depend on the specific
disease and the symptoms. For example, those afflicted with Type I Diabetes
must replenish their insulin levels, usually through injections. In autoimmune
diseases like Type I Diabetes, patients
may need supplements to provide a
hormone or vitamin that the body is
lacking. If the autoimmune disorder
either directly or indirectly affects the
blood or the circulatory system, such
as autoimmune hemolytic anemia
(AIHA), lupus, and antiphospholipidal antibody syndrome (AAS), patients
may require blood transfusions. In
autoimmune disorders that affect the
bones, joints, or muscle, such as mulSPRING 2011
tiple sclerosis (MS) and rheumatoid arthritis, patients often require assistance
to maintain mobility or medication to
suppress pain and reduce inflammation in affected areas (12). In many
cases of autoimmune diseases, medicine is often prescribed to control or
reduce the immune system’s response.
Such medicine may include corticosteroids and immunosuppressant drugs,
such as azathioprine, chlorambucil, cyclophosphamide, cyclosporine, mycophenolate, and methotrexate (11).
Autoimmune Disorders:
Women’s Disease?
Approximately one-third of the
risk of developing an autoimmune
disease can be attributed to heritable
factors, especially gender. Women account for about 75% of the estimated
23.5 million people in America afflicted
by autoimmune diseases, and autoimmune diseases constitute some of the
leading causes of death and disability
in women below 65 years of age (5, 13).
While the relationship between sex
and prevalence of autoimmune disorders remains unclear, researchers have
noted that women have higher levels
of antibodies and mount larger inflammatory responses than men when their
immune systems are triggered, possibly increasing the risk of autoimmunity
(3, 13). Autoimmune diseases tend to
fluctuate in accordance with hormonal
changes, such as during pregnancy,
menstrual cycle, menopause, aging and
usage of birth control pills (3). Autoimmune diseases fluctuate by racial lines
as well, since two gene variants were
found that are related to an increased
risk of lupus among African American
women (5). Despite the prevalence of
female patients, autoimmunity is rarely
discussed as a women’s health issue (7).
Environmental Triggers
Besides genetic factors, pathological and environmental factors play a
role in initiating or exacerbating certain autoimmune disorders. For example, the product of a human gene
that confers susceptibility to Crohn’s
disease recognizes components of certain bacteria, and viral infections have
long been suspected as triggers of Type
1 Diabetes. Conversely, other research
suggests that the numbers of regulatory T cells that normally hold potentially
destructive immune responses in check
are reduced by viral infections (5).
Exposure to various synthetic
chemicals and metals in the initiation
of autoimmune disease may also increase susceptibility to autoimmune
disorders. Generally, metals inhibit
immune cell proliferation and activation; mercury, gold, and silver, for
example, can induce lymphocyte proliferation and subsequent autoimmunity. A broad range of synthetic
chemicals, including hormone supplementation, hormone blockers, pesticides, insecticides, fungicides, and food
and herbal products, may elicit estrogenic or anti-estrogenic activity (5).
A Rising Epidemic and
Challenges in Combating
Autoimmune Disorders
In 2005, in a report to the US
Congress, the National Institutes of
Health (NIH) released Progress in Autoimmune Disease Research, which
reported that more than eighty known
autoimmune diseases, such as multiple
sclerosis, Type 1 Diabetes, rheumatoid
arthritis, Crohn’s disease and myasthenia gravis, affect anywhere from 14.7 to
23.5 million people in America (4, 5).
While a significant portion of
Americans suffer from autoimmunity
disorders, according to a 2001 survey
by the Autoimmune Diseases Association, over 45 percent of patients with
autoimmune diseases have been labeled chronic complainers in the earliest stages of their illness. Diagnosis is
difficult because a patient’s symptoms
are likely to be vague with a tendency to
fluctuate in the beginning. Thus, a typical patient usually undergoes a series of
tests before a correct diagnosis is made,
which can sometimes take years. (7)
Conclusions
Considering the prevalence of autoimmune disorders in America, both
the scientific community and the public must recognize the urgency of the
autoimmune epidemic. Today’s practicing physicians must be aware of the
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rising epidemic of autoimmune disease
and be able to diagnose their symptoms
properly and accurately before irreversible damage occurs. In addition, since
the patients afflicted with autoimmune
disorders are predominantly women,
these disorders should be discussed as
an issue relevant to women’s health.
Due to the vast number of autoimmune diseases, further research is
unlikely to pinpoint a single cause for
autoimmunity. Rather, research should
be focused on defining varied common
triggers, including environmental pollution and specific pathological agents.
References
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3. D. J. Nakazawa, The Autoimmune Epidemic
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4. Progress in Autoimmune Disease Research
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