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IDF PATIENT/FAMILY HANDBOOK | CHAPTER IV
Selective IgA Deficiency
Individuals with Selective IgA Deficiency lack IgA, but usually have
normal amounts of the other types of immunoglobulins. Most
affected people have no illness as a result. Others may develop a
variety of significant clinical problems. Selective IgA Deficiency is
relatively common in Caucasians.
 Definition of Selective IgA Deficiency:
Selective IgA Deficiency is the complete absence
of the IgA class of immunoglobulins in the blood
serum and secretions. There are five types
(classes) of immunoglobulins or antibodies in
the blood: IgG, IgA, IgM, IgD, and IgE. The
immunoglobulin class present in the largest
amount in blood is IgG, followed by IgM and
IgA. IgD is much lower, and IgE is present in only
minute amounts in the blood.
Of these immunoglobulin classes, it is primarily
IgM and IgG that protect us internally from
infection. It is also important that the body is
protected at surfaces that come into contact
with the environment. These sites are the
mucosal surfaces, which include: mouth, ears,
sinuses and nose, throat, airways within the
lung, gastrointestinal tract, eyes, and genitalia.
IgA antibodies are transported in secretions
to mucosal surfaces and play a major role in
protecting these surfaces from infection. Other
immunoglobulin classes are also found in
secretions at mucosal surfaces, but not in nearly
the same amount as IgA. This is why IgA is known
as the secretory antibody. If our mucosal surfaces
were spread out they would cover an area equal to
one and one-half tennis courts, so the importance
of IgA in protecting our mucosal surfaces cannot
be overstated.
IgA has some special chemical characteristics. It
is present in secretions as two antibody molecules
attached by a component called the J chain ("J"
for "joining"). In order for these antibodies to be
secreted, they must also be attached to another
molecule called the secretory piece. The IgA unit
that protects the mucosal surfaces is actually
composed of two IgA molecules joined by the J
chain and attached to the secretory piece.
Although individuals with Selective IgA Deficiency
do not produce IgA, they do produce all the other
immunoglobulin classes. In addition, the function
of their T-lymphocytes, phagocytic cells and
complement system are normal. Hence, the term
Selective IgA Deficiency.
The causes of Selective IgA Deficiency are
unknown. It is likely that there are a variety of
causes for Selective IgA Deficiency and the cause
may vary from individual to individual.
Low serum IgA, like absent serum IgA, is also
relatively common. Similarly, most people with
low serum IgA have no apparent illness. Some
people with low serum IgA have a clinical course
very similar to people with common variable
immunodeficiency (see chapter titled Common
Variable Immune Deficiency).
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Clinical Features:
Selective IgA Deficiency is one of the most
common primary immunodeficiency diseases.
Studies have indicated that as many as one in
every five hundred people have Selective IgA
Deficiency. Many of these individuals appear
healthy, or have relatively mild illnesses and
are generally not sick enough to be seen by a
doctor and may never be discovered to have IgA
deficiency. In contrast, there are individuals with
Selective IgA Deficiency who have significant
illnesses. Currently, it is not understood why some
individuals with IgA deficiency have almost no
illness while others are very sick. Also, it is not
known precisely what percent of individuals with
IgA deficiency will eventually develop complications;
estimates range from 25% to 50% over 20 years
of observation. Studies have suggested that
some patients with IgA deficiency may be missing
a fraction of their IgG (the IgG2 and/or IgG4
subclasses), and that may be part of the explanation
of why some patients with IgA deficiency are more
susceptible to infection than others.
A common problem in IgA deficiency is
susceptibility to infections. This is seen in about
half of the patients with IgA deficiency that come
to medical attention. Recurrent ear infections,
sinusitis, bronchitis and pneumonia are the
most common infections seen in patients with
Selective IgA Deficiency. Some patients also have
gastrointestinal infections and chronic diarrhea.
The occurrence of these kinds of infections is
easy to understand since IgA protects mucosal
surfaces. These infections may become chronic.
Furthermore, the infection may not completely
clear with treatment, and patients may have to
remain on antibiotics for longer than usual.
A second major problem in IgA deficiency is the
occurrence of autoimmune diseases. These are
found in about 25% to 33% of patients who seek
medical help. In autoimmune diseases, individuals
produce antibodies or T-lymphocytes which react
with their own tissues with resulting inflammation and
damage. Some of the more frequent autoimmune
diseases associated with IgA deficiency are:
Rheumatoid Arthritis, Systemic Lupus Erythematosis
and Immune Thrombocytopenic Purpura (ITP).
These autoimmune diseases may cause sore and
swollen joints of the hands or knees, a rash on
the face, anemia (a low red blood cell count) or
thrombocytopenia (a low platelet count). Other kinds
of autoimmune disease may affect the endocrine
system and/or the gastrointestinal system.
Allergies may also be more common among
individuals with Selective IgA Deficiency than
among the general population. These occur in
about 10-15% of these patients. The types of
allergies vary. Asthma is one of the common
allergic diseases that occurs with Selective IgA
Deficiency. It has been suggested that asthma
may be more severe, and less responsive to
therapy, in individuals with IgA deficiency than it
is in normal individuals. Another type of allergy
associated with IgA deficiency is food allergy, in
which patients have reactions to certain foods.
Symptoms associated with food allergies are
diarrhea or abdominal cramping. It is not certain
whether there is an increased incidence of allergic
rhinitis (hay fever) or eczema in Selective IgA
Deficiency.
Patients with IgA Deficiency are often considered
to be at increased risk of anaphylactic reactions
when they receive blood products (including IVIG)
that contain some IgA. This is thought to be due
to IgG (or possibly IgE) anti-IgA antibodies which
may be found in some of these people. However,
it has been observed that many patients with IgA
deficiency do not have adverse reactions to blood
products or IVIG. There is no agreement among
experts in this field regarding the magnitude of the
risk of these types of reactions in IgA deficiency, or
the need for caution or measurement of anti-IgA
antibodies before administration of blood or IVIG
to these individuals.
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Diagnosis of Selective IgA Deficiency:
The diagnosis of Selective IgA Deficiency is usually
suspected because of either chronic or recurrent
infections, allergies, autoimmune diseases, chronic
diarrhea, or some combination of these problems.
The diagnosis is established when tests of the
patient’s blood serum demonstrate absence of
IgA with normal levels of the other major classes
of immunoglobulins (IgG and IgM). Most patients
make antibodies normally. An occasional patient
may also have IgG2 and/or IgG4 subclass
deficiency and associated antibody deficiency
(see chapter titled IgG Subclass Deficiency and
Specific Antibody Deficiency). The numbers and
functions of T-lymphocytes are normal. Several
other tests that may be important include a
complete blood count, measurement of lung
function, and urinalysis. Other tests that may be
obtained in specific patients include measurement
of thyroid function, measurement of kidney
function, measurements of absorption of nutrients
by the GI tract, and the test for antibodies directed
against the body’s own tissues (autoantibodies).
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Treatment of Selective IgA Deficiency:
It is not currently possible to replace IgA in IgA
deficient patients, although research toward
purification of human IgA is ongoing. However,
it remains to be seen if replacement of IgA by
any route (IV, oral, or topical) will be beneficial
for humans with IgA deficiency. Treatment of
the problems associated with Selective IgA
Deficiency should be directed toward the particular
problem. For example, patients with chronic or
recurrent infections need appropriate antibiotics.
Ideally, antibiotic therapy should be directed
at the specific organism causing the infection.
Unfortunately, it is not always possible to identify
these organisms, and the use of broad-spectrum
antibiotics may be necessary. Certain patients who
have chronic sinusitis or chronic bronchitis may
need to stay on long term preventive antibiotic
therapy. It is important that the doctor and the
patient communicate closely so that appropriate
decisions can be reached for therapy.
As mentioned above, some patients with IgA
deficiency also have IgG2 and/or IgG4 subclass
deficiency and/or a deficiency of antibody
production. However, these laboratory findings do
not always predict a greater frequency or severity of
infections. For patients with IgA and IgG2 deficiency
who do not respond adequately to antibiotics, the
use of replacement gamma globulin may be helpful
in diminishing the frequency of infections (see
chapter titled Specific Medical Therapy).
There are a variety of therapies for the treatment
of autoimmune diseases. Anti-inflammatory drugs,
such as aspirin or ibuprofen, are used in diseases
that cause joint inflammation. Steroids may be
helpful in a variety of autoimmune diseases. If
autoimmune disease results in an abnormality of
the endocrine system, replacement therapy with
hormones may be necessary. Treatment of the
allergies associated with IgA deficiency is similar
to treatment of allergies in general. It is not known
whether immunotherapy (allergy shots) is helpful in
the allergies associated with Selective IgA Deficiency,
although there is no evidence of any increased risk
associated with this therapy in these patients.
The most important aspect of therapy in IgA
deficiency is close communication between
the patient (and/or the patient’s family) and the
physician so that problems can be recognized and
treated as soon as they arise.
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Expectations for Selective IgA Deficiency Patients:
Although Selective IgA Deficiency is usually
one of the milder forms of immunodeficiency,
it may result in severe disease in some people.
Therefore, it is difficult to predict the long-term
outcome in a given patient with Selective IgA
Deficiency. In general, the prognosis in Selective
IgA Deficiency depends on the prognosis of the
associated diseases. It is important for physicians
to continually assess and reevaluate patients
with Selective IgA Deficiency for the existence of
associated diseases and the development of more
extensive immunodeficiency. For example, rarely,
IgA deficiency will progress to become Common
Variable Immunodeficiency with its deficiencies of
IgG and/or IgM. The physician should be notified
of anything unusual, especially fever, productive
cough, skin rash or sore joints. The key to a good
prognosis is adequate communication with the
physician and the initiation of therapy as soon as
disease processes are recognized.
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