The Immune System and Autoimmune Diseases
Linda Aronson, DVM, MA
Introduction to the immune system
The immune system is designed to protect the body from
disease causing pathogens and other foreign substances.
It is an amazingly complex system, and we are probably
only just beginning to appreciate its many parts and
functions. For example, recent research has shown
changes in the immune cells in human patients suffering
from severe mental illness. It is hoped these changes
can form the basis for a diagnostic test for these
illnesses and allow for earlier intervention. In this
paper I will merely hope to give an overview of the
parts of the system involved in preventing infection,
and the ways in which the system can fail.
The body has a number of lines of defense. The skin is
a wonderful barrier. The gut-associated lymphoid tissue
(GALT) is the biggest immune organ in the body, and
about 70% of the body’s immune system is to be found in
the intestinal lining. The digestive tract must strive
to exclude unwanted pathogens while allowing nutrients
to enter the body and coexisting with commensal (good)
bacteria that help digest food and make necessary
enzymes and vitamins, while preventing overgrowth by
toxic bacteria and fungi. Acid in the stomach kills
many microorganisms, while the mucus lining of the gut
contains antibodies to neutralize others. Enzymes,
especially those in bile and saliva, detoxify some
pathogens while others break down food substances into
their smallest elemental units. Coordinated waves keep
food moving through the gut. In the developed world the
delicate balance of the gut is often disrupted and
inflammatory bowel disease is becoming increasingly
common in our dogs. In humans there have been studies
demonstrating that improved hygiene and the loss of
intestinal parasites which have coexisted for millennia
may be responsible and replacing them with benign
parasites may be curative. There may also be mutations
in the genes that control innate immune recognition,
adaptive immunity and epithelial permeability all of
which may contribute to the inflammatory response as
well as food allergies. The respiratory and
genitourinary tracts are similarly protected by a
combination of mechanical and chemical barriers.
The skin, lungs and intestines (as well as circulating
white blood cells) are populated by specific peptides –
small portions of protein - (e.g. cathelicidins) that
act as natural antibiotics. They help to contain fast
moving infections until the immune system can mount a
fully orchestrated attack. While bacteria have been
able to develop resistance to artificial antibiotics,
they have never been able to develop immunity to these
peptides. It is hoped that boosting this natural
defense system may provide a successful means of
combating antibiotic resistant infections such as MRSA
(methicillin resistant Staph. Aureus);
necrotizing fasciitis (the flesh eating bacteria); or
toxic shock syndrome.
If the physical barriers to infection fail, the next
line of defense is provided by the innate immune system,
which identifies infectious agents by their pattern or
structure and provides an immediate but non specific
response (inflammation, release of chemicals to bring
various immune cells or which kill invading organisms).
If pathogens evade this system there is a final adaptive
immune system which is specific for particular pathogens
and antigens, but which takes several days to gear up
initially to a new infectious organism. However, once a
particular microbe has been encountered specific
antibodies are formed against it, and can be called into
action on subsequent exposures. Antigens are molecules
that generate an antibody response. Both
innate and adaptive immune systems have humoral
components found in the body fluids – primarily blood
and lymph, and cellular ones.
The complement system is the primary component of the
innate humoral response; it so called because it
complements antibodies in killing pathogens. A
biochemical cascade of over 20 different enzymes attacks
the surface of microbes to which antibodies have
attached. As well as releasing chemicals that eat the
organism, the cascade also attracts other immune cells,
increases the permeability of blood vessels facilitating
their access to the organism, as well as marking it for
destruction. The cellular component consists of various
types of white blood cells: phagocytes (macrophages,
neutrophils and dendritic cells), mast cells,
eosinophils, basal cells and natural killer (NK) cells.
Phagocytes engulf and digest smaller pathogens. They
circulate throughout the body, but are attracted by
substances released by the complement cascade.
Neutrophils usually represent the majority of white
cells in the blood, while macrophages are usually found
in the tissues. They also scavenge dead cells, and
present cells to antibodies. Dendritic cells are
phagocytes in skin, nose, lungs and gastrointestinal
tract where they have contact with the external
environment. Mast cells are found in connective tissues
and mucous membranes and they regulate the inflammatory
response. Over-activity results in allergic and
anaphylactic reactions. Basophils and eosinophils are
also circulating in the blood stream and their primary
role is defense against parasites, although they also
have a role in allergies. NK cells destroy tumor cells
and those infected with viruses.
The adaptive immune system allows for a stronger immune
response and also provides immunological memory so that
an antigen that has already been encountered will
produce a faster and more focused response. It is the
adaptive immune system that must be able to tell self
from non-self. Lymphocytes are the cellular component of
the adaptive immune system. There are two major types,
B cells are formed in the bone marrow and are involved
in the humoral response. They are also known as
immunoglobulins – IgG, IgM, IgA, IgD and IgE. T cells
originating in the thymus produce the cell-mediated
response involving the lymph nodes, thymus, spleen,
GALT, tonsils and mucus secretion. Both types have
receptors that recognize specific targets. The B-cell
receptor recognizes whole pathogens. T-cells only
recognize small fragments of pathogens that have been
processed and presented by other (MHC) molecules. There
are two major types: killer T cells kill cells infected
with pathogens as well as those that are damaged or
dysfunctional. Each T cell recognizes a single
antigen. Helper T cells, having recognized the antigen,
release chemicals to stimulate and increase the activity
of B cells, killer T cells and macrophages, and regulate
both innate and adaptive immune systems. A third class
of T cells, suppressor T cells dampen the immune
response if it becomes overactive or out of regulatory
control.
Activation of the B and T cells causes them to reproduce
and their progeny become long-lived memory cells ready
to mount an immune response to any subsequent encounters
with the pathogen. Newborn puppies have not been
exposed to pathogens and lack this active memory. They
have however, received passive immunity from their
dams. A particular kind of antibody – IgG - is
transported across the placenta providing the neonate
puppy with immunity to antigens encountered by the dam.
The first milk, colostrum, also contains antibodies (all
classes) against primarily bacterial infections, as well
as lymphocytic cytokines – which are immune regulators;
interleukins that control inflammatory response;
interferon which inhibits viral reproduction; and other
substances that support an effective immune response.
These large molecules can only cross the intestinal wall
for the first 24-48 hours so it is important that the
puppy receives colostrum. If the bitch has none,
hyperimmune plasma can be tubed in during this time slot
to provide passive immunity. The puppy does not make
antibodies or memory cells in response to these
antibodies, and the immunity gradually wanes over the
first weeks of the puppy’s life, unfortunately
persistence is highly variable. Long term active
immunity is obtained by activation of B and T cells when
they encounter an infection or artificially through
vaccination.
Disorders of immunity
The immune system is a complex one that is both specific
and adaptive to the dog’s changing environment. Its
complexity unfortunately makes it susceptible to
failure. There are basically three potential problems.
In immunodeficiency one or more of the components
are inactive. Ability to respond is reduced in the
young and elderly. Malnutrition, particularly the lack
of sufficient protein, iron, copper, zinc, selenium,
Vitamins A, C, E, B6 or folic acid, is one
cause. Environmental toxins, genetic or acquired
diseases, and certain cancers can also result in
immunodeficiency. Hypersensitivity is the result
of an excessive response that results in damage of the
body’s own cells. There are four classes. Anaphylactic
reactions are often associated with allergy and can
range from mild to fatal. They are caused by IgE
released from mast cells and basophils. Cytotoxic
hypersensitivity results from IgG or IgM antibodies
attaching to the body’s own cells and marking them for
destruction. Type III is caused by the deposition of
immune complexes of antigens, compliment proteins and
IgG and IgM antibodies in the tissues. Type IV
hypersensitivity includes many autoimmune and infectious
diseases as well as contact dermatitis and is mediated
by T cells, monocytes and macrophages. Autoimmune
reactions are a specific form of over-reactivity in
which the immune system fails to distinguish self from
non-self resulting in it attacking parts of its own
body. Specialized cells in the bone marrow and thymus
normally eliminate any lymphocytes that present with
self antigens.
Different hormones can stimulate or suppress the immune
system. Estrogen hormones can stimulate both innate and
adaptive immune systems, which is why some autoimmune
diseases are more common in bitches and occur after she
is sexually mature. It appears that testosterone may
suppress the immune system, while progesterone prevents
the bitch rejecting the fetuses as foreign, but also
dampens the general immune response. Prolactin and
growth hormone also affect the immune system in a
complex fashion. Declining levels of hormones in older
animals may contribute to a reduced immune response in
older animals. The immune system regulates thyroid
activity and vice versa. Stress impairs immune
reaction, while rest enhances it. Malnourished fetuses
and neonates will suffer a lifelong impairment, while
certain foods – especially essential fatty acids as well
as some other foods and herbs can stimulate it.
Drugs can also be used to manipulate the immune system.
Immunosuppressive drugs are used to control autoimmune
diseases and to reduce inflammation as well as to
prevent rejection of transplanted organs.
Glucocorticoid drugs are the most potent
anti-inflammatory drugs, but they have serious
side-effects. Other drugs, such as azathioprine, are
cytotoxic and suppress the immune response by
indiscriminately killing rapidly dividing cells such as
activated T cells, but also those in other organs
causing toxic effects. A third class of drug inhibits
the signals that activate T cell response, cyclosporine
does this. Antibiotics enhance immune response, but will
not be considered here. Neither will the various
strategies employed by pathogens to elude the immune
response at all levels.
Autoimmune
Diseases
At this time we are only beginning to untangle the
causes of these diseases. In the majority of cases
there appears to be a genetic factor necessary, but
disease will not be seen without some external trigger.
Sometimes we can pinpoint this – a vaccine, drug, toxin
or illness (usually viral or bacterial) – but often the
trigger is not identified. Hormones and stress are also
triggers for disease. Are autoimmune diseases more
common now or are we better at detecting them? The
answer is probably both. Certainly, we and our dogs live
in an increasingly artificial environment laden with
chemicals; food is laced with ingredients that are
anything but natural. I come across repeated instances
of households where owners and their animals have an
assortment of different ailments that are all autoimmune
in nature. However, veterinarians and owners are also
more aware of the problem. Over and over I hear that an
unexplained problem is probably autoimmune with no real
idea of what disease is suspected. Just because a
problem responds to immunosuppressive drugs doesn’t mean
that it was the result of autoimmune disease.
Certain immune-suppressant viruses (retroviruses and
parvoviruses) have been implicated as causing bone
marrow failure, the immune mediated blood diseases
(autoimmune hemolytic anemia – AIHA - and
immune-mediated thrombocytopenia – ITP), lymphoma,
leukemia, dysregulating humoral and cell-mediated
immunity, liver and kidney failure, and autoimmune
endocrine disorders – thyroiditis, hypoadrenocorticism
(Addison’s disease) and diabetes. Viral disease and
recent vaccination with single or combined modified live
viruses are also triggers for immune-mediated blood
disease, bone marrow failure and organ dysfunction. The
killed rabies vaccine and bacterial leptospirosis
vaccine more commonly trigger immediate or delayed
vaccinosis reactions. The bacterial (Ehrlichia,
Anaplasma, Rocky Mountain Spotted Fever)
Protozoal (Babesia) and spirochetal (Lyme disease) tick
borne diseases suppress the host immune system and
decrease the numbers of antibodies making the animal
susceptible to secondary infection, while inducing
autoimmune diseases of the blood (AIHA and ITP), gut
(IBD), muscles (myositis), eye (uveitis), joints
(polyarthritis) and in the case of Lyme a protein losing
disease of the kidney -the latter two closely mimic
systemic lupus erythematosus (SLE). When the apparent
autoimmune disease has been addressed titers for the
tick borne diseases are often found to be sky high, as
these organisms can adapt and survive within the body
for years or even permanently. Skin “allergies” are
also indicative of an immune system gone awry.
Drugs associated with exacerbating or triggering
autoimmune disease include potentiated sulfonamides
(trimethoprim-sulfa and related antibiotics), monthly
heartworm drugs (especially those combined with flea
preventatives) and anticonvulsant drugs. As stress and
the need for drugs tend to go hand in hand virtually any
drug is capable of acting as a trigger in a susceptible
individual.
Autoimmune thyroiditis
Hypothyroidism is arguably the most common endocrine
disease in dogs and in the majority of cases it is
autoimmune in nature. Because the thyroid hormones
regulate metabolic function in all the body’s cells even
suboptimal function can result in profound changes
throughout the body that can be missed – written off as
puppy exuberance/ADD or normal aging – or mistaken for
some other disease. By the time the classical
presentation of obesity, lethargy, heat-seeking and
alopecia is achieved two-thirds of thyroid function or
more has been lost. Monitoring thyroid function
regularly through comprehensive thyroid panels is one of
the most important things we can do to ensure good
health for our dogs. Reduced thyroid function results
in depression of the immune response to other diseases.
It often accompanies other autoimmune disorders and any
dog diagnosed with autoimmune disease should have a
thyroid panel run. Supplementing the thyroid usually
results in a better prognosis for these diseases as well
as reducing the need for other, often more expensive or
toxic, drugs. Early signs are often behavioral in
nature – increase in fear, aggression or obsessive
behaviors, as well as an inability to focus and learn in
young animals. Young animals, unlike older dogs, often
are uninterested in food, underweight and hyperactive.
Commonly seen signs include:
____Excessive shedding, patchy hair loss or “rat tail”
____Dry skin or dull, dry hair coat
____Recurrent infections (especially ear, skin and foot
infections)
____Tendency to gain weight
____Heat seeking behavior (acts cold)
____Increased sleep time
____Hyperactivity
____Slow learning
____Seizures
____Worried look, tragic facial expression or looking
“old”
____Reduced hearing, sight and scenting ability
____Chronic gastrointestinal symptoms
____Loss of muscle or bladder tone
____Head tilt
____Change in character of bark
____Exercise intolerance
____Infertility, false pregnancy or weak, dying or
stillborn puppies
____Recurring eye infections
____Premature graying
Diagnosis via
a complete thyroid panel consisting minimally of serum
levels of total and free T3 (triiodothyronine) and T4
(thyroxine) preferably with levels of T3 , T4 and
thyroglobulin antibodies. Because
dogs
under 18 months, toy and giant breeds as well as
sighthounds have different thyroid requirements it is
recommended that serum be sent to Hemopet Diagnostics
service for evaluation
www.hemopet.org If a dog has low or suboptimal
thyroid function, treatment with L-thyroxine twice daily
at a dose of 0.1mg/12-15 lbs body weight should resolve
any of the above problems.
Autoimmune hemolytic anemia (AIHA aka Immune mediated
Hemolytic Anemia –IMHA)
Anemia per se is a clinical sign not a disease, and is
simply a decrease in the number of red blood cells
(RBCs) or the amount of hemoglobin, resulting in a
decrease in the oxygen-carrying capacity of the blood.
Anemia can be caused by blood loss, decreased production
of new RBCs, or an increase in the rate of their
destruction - hemolytic anemia.
Senescent RBCs acquire markers on the cell surface that
are recognized and are removed from circulation usually
by the spleen and/or liver. Similarly markers appear on
RBCs in cases of AIHA. These markers can be true
autoantibodies, as in primary AIHA, or can be secondary
to drugs (the immune stimulator and wormer levamisole,
certain antibiotics, and the anticonvulsant
anti-arrhythmia drug phenytoin have been implicated),
infectious disease, cancer, blood parasites, or heavy
metals (lead, and zinc). AIHA results when red cells
are removed faster than they can be replaced.
Antibodies can be warm (usually IgG reactive at body
temperature) or cold type (usually IgM when body
temperature drops below normal). As well as being
removed by spleen and liver, RBCs are destroyed in the
blood vessels when the immunoglobulins (usually IgG)
activates compliment. RBCs may also clump as a result
of bridges formed between cells usually by IgM.
Clinical signs of AIHA can appear gradually or suddenly
and relate to the lack of oxygen reaching the tissues –
collapse/weakness, lethargy, anorexia, exercise
intolerance and an increase in the heart and respiratory
rates. Mucous membranes (gums, eyelids, etc.) are
usually pale and heart murmurs may be heard. Vomiting
and diarrhea are not uncommon. Lymph nodes are usually
swollen. In more severe cases a fever and "icterus"
(jaundice) - a yellow discoloration of the gums, eyes,
and skin due to a buildup of bilirubin, one of the
products of hemoglobin breakdown – will be found.
Anemia is confirmed by complete blood count (CBC). A
Coombs test and clotting time tests may also be used to
confirm diagnosis although only about 60% of patients
with AIHA have a positive Coombs test. Palpation and
radiographs confirm enlargement of the spleen and
liver. In chronic cases the heart may be enlarged.
Anemia can be regenerative or non regenerative. In the
latter case, there is immune mediated destruction of RBC
precursors in the bone marrow.
In severe cases blood transfusion with cross-matched
packed red cells or whole blood and intravenous fluids
may be necessary. Corticosteroids are usually the
first drug given and are started at very high
immunosuppressive doses, the dose is very slowly tapered
over many weeks or months to a low maintenance dose.
Some affected dogs have to be kept on low steroid doses
for the rest of their lives and most are susceptible to
relapse. Other immunosuppressive drugs such as
azathioprine (Imuran) or cyclophosphamide (Cytoxin) may
be added. If the drugs have failed to produce
significant improvement after 4 to 6 weeks splenectomy -
the surgical removal of the spleen - may be recommended.
Immune-mediated thrombocytopenia (ITP)
ITP is the destruction of platelets also known as
thrombocytes by the binding of antibodies to the
platelets’ surface leading to their premature removal
from circulation. ITP often accompanies AIHA.
Platelets attach to cell walls when they are damaged and
help produce a clot to prevent blood loss either within
the body or through the skin and other external
surfaces. Generally we are unaware of all the minor
breaches that occur all the time. If platelet numbers
drop sufficiently low (<40,000) spontaneous hemorrhaging
can occur usually into the skin, g/i tract, respiratory
or urinary systems. Typically presentation results from
hemorrhage into the skin (petechiation) causing small or
large blood blisters, excessive bleeding from minor
traumas, vomiting, urinating or defecating blood,
lethargy, weakness or collapse – although these last
three signs are more likely if there is accompanying
AIHA. Other causes of clotting disorder - rat poison,
hemophilia, von Willebrand’s disease, bladder and
prostate infection, cancer or intestinal parasites -
should be ruled out. CBC, Coombs test, vWF and clotting
tests are performed and bone marrow samples may also be
taken. Drug treatment is usually the same as for AIHA.
A single injection of vincristine may be given in
extreme cases as it will produce a large increase in
platelet numbers three days later. Transfusion of whole
blood or platelet rich plasma may also be indicated.
Once platelet counts are normal ovariohysterectomy
(spaying) is recommended in intact bitches to prevent
hemorrhage during estrous. Due to the genetic component
in autoimmune diseases it is strongly recommended that
affected dogs should not be used in a breeding
program.
Systemic lupus erythematosus (SLE)
SLE also often accompanies/causes AIHA and/or ITP. It
is a multi-systemic autoimmune disease often simply
referred to as lupus. It is the result of autoantibodies
to non-organ specific nuclear and cytoplasmic antigens
as well as cell and organ specific antigens. The
resulting immune complexes are deposited in multiple
locations throughout the body, but most commonly the
glomerular membranes in the kidney, synovial membranes
in joints, the skin, mucous membranes, blood and brain.
Complement is activated leading to inflammation as well
as direct toxic damage to surrounding structures.
Clinical signs depend upon where the immune complexes
are located and the specificity of the autoantibodies.
The signs of SLE may be acute (sudden onset) or chronic
but are almost always cyclic – wax and wane. A
fluctuating fever that does not respond to antibiotics
is often seen. Joints may be swollen and painful
resulting in a stiff gait or shifting lameness.
Symmetrical or local skin lesions with redness, scaling,
ulceration and loss of hair are also common as are
ulcerative lesions in the mouth and junctions between
haired skin and mucous membranes. Glomerulonephritis
results from leaky membranes in the glomeruli –
filtration units of the kidney – leading to poor
filtration and loss of protein into the urine. Heart
murmurs and arrhythmias and pleural friction rubs are
due to inflammation of heart muscle and the sacs around
heart and lungs. Muscle wasting and inflammation,
enlarged lymph nodes and spleen, low white cell counts,
depression, seizures and changed mentation round out the
possible symptoms.
While a CBC and antinuclear antibody test (ANA) should
be run, along with appropriate diagnostic tests for
specific systems affected diagnosis is based on the
number of major and minor signs of SLE present. A false
positive ANA can result from a number of infectious
diseases such as some of the tick borne diseases, which
also present with polyarthritis. While
immunosuppressant drug therapy is the cornerstone of
treatment of SLE, treatment is also directed at the
particular systems affected by the disease where
possible. Prognosis is guarded especially where kidney
disease is advanced or there is secondary infection
(pyelonephritis), septic arthritis in the joints or
septicemia in the blood.
Autoimmune diseases of the skin
These are a group of autoimmune diseases that are
definitively diagnosed by skin biopsy and/or
immunofluorescent staining, and which generally respond
quite well to corticosteroids and/or other
immunosuppressants. There are four members of the
pemphigus group characterized by varying degrees of
ulceration, crusting, pustules and vesicles. Pemphigus
foliaceus is the most common and usually involves the
head, ears and footpads, although it can become
generalized. It rarely affects mucous membranes, but
may affect nail beds. (When it does it may be a case of
mistaken identity and actually be symmetrical lupoid
onychodystrophy – SLO – also thought to be an autoimmune
disease and only affecting the nails. Definitive
diagnosis requires amputation of the final toe bone (P3)
holding the claw, and many owners are unwilling to do
this.) Secondary skin infections are common. Pemphigus
erythematosus is most likely a milder form of P.
foliaceus and is localized to head, face and footpads
especially on the nose where it is aggravated by
ultraviolet light. Pemphigus vulgaris is the most
severe form causing more severe lesions and also
affecting the mouth, mucous membranes and mucocutaneous
junctions, axillae (arm pits) and groin. The blisters
are thin, fragile, and rupture easily, while the skin
lesions are usually red, weeping, ulcerated plaques.
Pressure on the skin around a lesion causes new or
extended lesions to form. Dogs are often itchy and
painful, and may be anorexic, depressed, feverish and
develop secondary bacterial infection at the lesions.
Pemphigus vegetans may be a benign form of P. vulgaris
and consists of oozing pustules and thick vegetative
lesions, but no systemic illness nor involvement of the
mouth. P. foliaceus and vulgaris may require life long
treatment with immunosuppressants, while P vegetans and
erythematosus may need oral corticosteroids or respond
to topical corticosteroids.
Discoid lupus erythematosus may be a benign form of SLE
and causes dermatitis of the face - usually over the
bridge of the nose. Lesions are similar to and often
mistaken for nasal solar dermatitis (also known as
collie nose) and pemphigus erythematosus. Tattooing the
area may prevent sunburn.
Vogt-Koyanagi-Harada-like syndrome (VKH) is extremely
rare and may be autoimmune in origin. It causes
depigmentation of the nose, lips, eyelids, footpads, and
anus and they fade to pink or white, and there is an
accompanying acute uveitis (inflammation of the eyes).
Early treatment may prevent blindness, but the pigment
loss is usually permanent.
Polyarthritis
Immune-mediated polyarthritis can be seen in SLE as
above or as an independent finding. There are several
different diseases included under this umbrella term,
but the major signs for all of them include high fever,
joint pain and swelling, and a lameness that seems to
shift from leg to leg. Lymph nodes may be enlarged.
Rheumatoid arthritis (RA) is the most severe form and
X-rays of the joints will show erosion of cartilage and
eventually bone. Rheumatoid factor can usually be found
in the blood. X-rays in the milder non-erosive forms
will appear normal. Other blood work may be normal or
show abnormalities and what changes there are will not
be consistent. In uncomplicated immune-mediated
polyarthropathies, clinical remission can be achieved
with corticosteroids in about half the cases. For the
rest, azathioprine or cyclosporine is usually effective,
and remission can be maintained with corticosteroids.
With the exception of rheumatoid arthritis, the
prognosis is generally good.
Muscle related autoimmune diseases
Myositis can be generalized – polymyositis (affecting
skeletal muscles of limbs and jaw; dermatomyositis also
has skin lesions) or focal affecting either the
masticatory muscles (temporalis muscle over the head and
jaw muscles) or extraocular muscles around the eye. The
muscles affected are usually stiff and painful and may
be acutely swollen, but they atrophy over time.
Autoantibodies are directed against muscle fibers.
Polymyositis may also be caused by infectious diseases,
certain cancers and some drugs, so muscle biopsy is
needed to confirm an autoimmune etiology. Focal
myositis is often diagnosed by response to
immunosuppressive drugs. Corticosteroids should produce
full remission provided there has been no fibrosis of
the muscles prior to treatment. One potential
complication of polymyositis is megaesophagus, an
enlargement of the entrance to the esophagus which
prevents closing the trachea when swallowing food. This
can result in food entering the trachea and causing
infection (aspiration pneumonia).
Myasthenia gravis may rarely be congenital but is
usually an autoimmune disease resulting from
autoantibodies attaching to the acetylcholine receptors
that transmit nerve signals to muscles causing them to
contract. The receptors are destroyed and often the
surrounding cell membrane as well. Dogs may present with
focal weakness of muscles in the esophagus, pharynx or
around the eye or with generalized muscle weakness so
the dog cannot support its own weight. Megaesophagus
and aspiration pneumonia are common. Serum
acetylcholine antibody receptor titer is diagnostic as
is response to the anticholinesterase drug edrophonium
(which prolongs the action of acetylcholine in the
neuromuscular junctions). Treatment is with a related
more long acting drug called pyridostigmine. Prednisone
is usually given at immunosuppressive doses, but it may
initially make the weakness worse.
Other
In humans type 1 (insulin dependent) diabetes mellitus
(DM) is an inflammatory autoimmune disease resulting in
destruction of insulin producing beta cells in the
islets of Langerhans. Autoantibodies to insulin have
been found in the dog suggesting that DM is
predominantly an autoimmune disease in the dog.
Pancreatitis may also be a possible cause. The number
of cases of DM appears to have increased dramatically
since kibbled foods became the predominant form of
canine nutrition, and as these must be 60% carbohydrate
as opposed to about 5% carbohydrate in the diet of most
wild canids, metabolic disease may also be responsible
or at least a contributing factor.
Kerratoconjunctivitis sicca (KCS) commonly known as dry
eye results from cessation of tear production and
responds to the cyclosporine suggesting an immune
mediated etiology. Vitiligo may represent an autoimmune
destruction of the cells that produce the pigment
melanin. In time it is likely other autoimmune
diseases will be added to the list.
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A grateful thank you to Linda Aronson DVM for this
article.
