678
Chapter 18
Systemic Lupus Erythematosus
Among the many immunological diseases discussed in this
chapter were those that fell under the general category of
autoimmune disease. Because these are so common, and
their consequences can be so severe, it is worth exploring
them in greater detail. One well-known autoimmune
disease with particularly serious symptoms is known as
systemic lupus erythematosus
(
SLE
).
SLE affects roughly
two to three people per 10,000 population. As with most
autoimmune diseases, the majority (~90 percent) of SLE
sufferers are female. Although the disease can be manifested
at any age, it most commonly appears in women of
childbearing age. SLE is distinguished from another form of
lupus, known as drug-induced lupus erythematosus. In the
latter, certain individuals being treated with drugs such as
hydralazine
(a vasodilator effective in reducing high blood
pressure) have been known to develop lupus-like symptoms.
True SLE, however, is a disease of the immune system.
The two major immune dysfunctions in SLE are
hyperactivity of T and B cells, with overexpression of
“self” antibodies, and decreased negative regulation of the
immune response. In some other autoimmune diseases,
one or a small number of antigens appear to be the root
of the disorder, and these are often localized to one or a
few organs. In SLE, however, the situation is much more
grave. This is because there are many self proteins that
become antigenic, and many of these are in the nuclei of
all cells. Thus, the chief (but not only) site of autoantibody
production in SLE is directed against proteins associated
with cellular DNA and RNA. Because all cells share the
same DNA and RNA, there are few—if any—parts of the
body that are not susceptible to immune attack in SLE.
Exactly what initiates the immune response in SLE is
unclear. However, it is known that most people with this
disease are photosensitive; that is, their skin cells are readily
damaged by ultraviolet light from the sun. When these cells
die, their nuclear contents become exposed to phagocytes
and other components of the immune system. As a result,
symptoms of SLE tend to fl are up when a person with the
disease is exposed to excessive sunlight.
SLE has a strong genetic component, as evidenced
by the fact that approximately 40 to 50 percent of identical
twins share the disease when one is affl icted. Moreover,
there is an increased frequency of fi ve specifi c class II MHC
variants in people with SLE, as well as defi cient or abnormal
complement proteins. Still, there are almost certainly
ADDITIONAL CLINICAL EXAMPLES
environmental triggers that elicit the disease in genetically
susceptible people (because, as stated, in half the cases
where one twin has SLE, the other does not). There is no
conclusive evidence that infections due to viral invasion
are a trigger for the development of SLE. Other than
sunlight, other triggers that appear to be associated with the
appearance of SLE are certain chemicals and foods, such as
alfalfa sprouts.
SLE can be mild or severe, intermittent or chronic.
In all cases, though, the effects are widespread. Typically,
connective tissue damage is extensive, with repeated
infl ammatory reactions in joints, muscle, and skin. The
outer covering of the heart (pericardium) may become
infl amed, gastrointestinal activity may be affected, and
retinal damage is sometimes observed. Even the brain is not
spared, as cognitive dysfunction and even seizures may arise
in severe cases. The skin often develops infl amed patches,
notably on the face along the cheeks and bridge of the
nose (forming the so-called “
butterfl
y rash
” seen in some
patients with SLE). Perhaps the greatest danger occurs when
immune complexes and immunoglobulins accumulate in the
glomeruli of the nephrons of the kidney. This often leads
to
nephritis
(infl ammation of the nephrons) and results in
damaged, leaky glomeruli. The appearance of protein in the
urine, therefore, is a clinical fi nding associated with SLE.
Finally, certain proteins on the plasma membranes of red
blood cells and platelets may also become antigenic in SLE.
When the immune system attacks these structures, the result
is lysis of red blood cells and destruction and loss of platelets
(
thrombocytopenia
). Loss of red blood cells in this manner
contributes to the condition known as
hemolytic anemia,
a
not uncommon manifestation of SLE.
In addition to the production of self antibodies in large
numbers, there also appears to be a failure of the immune
system to regulate itself. Thus, the immune attacks, once
begun, do not stop after a few days but instead continue
indefi nitely. Some investigators believe this may be related to
a defi ciency or inactivity of suppressor T cells, but this has
not been proven.
The treatments for SLE depend on its severity and the
overall physical condition of the patient. In mild fl
are-ups,
aspirin and other nonsteroidal anti-infl ammatory drugs may
be suffi cient to control pain and infl
ammation, together
with changes in lifestyle to avoid potential triggers. In more
advanced cases, immunosuppression with high doses of
synthetic adrenal corticosteroids is employed.
SUMMARY
Cells Mediating Immune Defenses
I. Immune defenses may be nonspecifi c, so that the identity of
the target is not recognized, or they may be specifi c, so that it
is recognized.
II. The cells of the immune system are leukocytes (neutrophils,
eosinophils, basophils, monocytes, and lymphocytes), plasma
cells, macrophages, dendritic or macrophage-like cells, and
mast cells. The leukocytes use the blood for transportation but
function mainly in the tissues.
III. Cells of the immune system (as well as some other cells) secrete
protein messengers that regulate immune responses and are
collectively called cytokines.
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