Selective IgA Deficiency occurs once in every 400 to 2,000 individuals.
However, its incidence varies across racial and ethnic lines.
It is found most frequently in persons who are white and of European
ancestry. Frequency rates for this group have been cited at 1 in 500 to
1 in 700, depending on the source. Therefore, most research studies of
IgA deficient persons have been done in persons of European descent.
In one U.S. study, black persons were reported to have a much lower
incidence of Selective IgA Deficiency than whites by a ratio of 1 to
20. Also, in studies of some Asian population, a much lower incidence
of Selective IgA Deficiency has been found. In persons of Japanese
descent, Selective IgA Deficiency occurs in only 1 in 18,500 persons.
The deficiency is also relatively uncommon in Malaysians.
IgA Deficiency is the most common of the primary Immunodeficiencies. It
is defined as the total absence or severe deficiency of IgA. Blood
serum levels for IgA deficient persons are usually found to be 7 mg/dl
or less, while serum IgA in normal adults ranges from 90 to 450 mg/dl.
IgA is deficient in these individuals because their B-lymphocytes,
cells which normally produce IgA, are unable to mature into IgA-producing
plasma cells. IgA deficient persons appear to have IgA-bearing B-cells
that are arrested at an immature stage of development.
The disorder is termed "selective" because other serum
immunoglobulins, such as IgM and IgG, are present at normal or increased
levels. Additionally, IgA deficient persons have normal or near normal
T-cell, phagocytic cell and complement system function
The IgA class of immunoglobulins has the specific function of
protecting the body's mucosal surfaces (eyes, mouth, throat, lungs,
gastrointestinal, and genitourinary tract) from infection. While IgA is
aided in this role to some degree by other classes of immunoglobulins,
the lack or severe deficiency of IgA at these body sites makes one or
more prone to recurrent infection, allergies, chronic diarrhea, or
autoimmune diseases. In autoimmune diseases, the immune system
mistakenly attacks the body's own tissues.
Medical research has not yet determined the exact cause or causes of
Selective IgA Deficiency. In some families, there is evidence of
familial occurrence, suggesting both autosomal dominant (only one
abnormal gene is required which dominates the other) and recessive modes
(two abnormal genes, one from each parent, are required) of
transmission. Selective IgA Deficiency also occurs frequently in
immediate relatives of persons with Common Variable Immunodeficiency,
suggesting similarity in causes of the two disorders.
In rare cases, partial IgA deficiency has been linked to deletions of
the IgA1 or IgA2 genes on chromosome 14, as well as to genes in the
major histocompatibiilty complex on chromosome 6. This region
determines powerful antigens that produce strong T-cell responses.
Other reports link the disorder to partial deletion of the long or short
arm of chromosome 18, which results in what is called the 18-q
syndrome: carp shaped mouth, reduced prominence of the mid facial area,
nystagmus (involuntary, rapid, rhythmic eye movement, hypotonia (reduced
muscle strength), atretic (congenital absence or closure), or stenotic
(abnormal narrowing or constriction) ear canals, hearing loss, and
mental retardation. However, the vast majority of persons with
Selective IgA Deficiency have evidence of chromosomal abnormalities.
The association of IgA deficiency has been found in some patients
with ataxia-telegiectasia (irregularities or failure of muscle
coordination affecting eyes and skin), frequent respiratory infections,
and immunodeficiency (re: Louis Bar Syndrome), a hereditary,
Additionally, Selective IgA Deficiency can occur as a consequence of
congenital intrauterine infection with rubella (German or three day
measles), toxoplasmosis (disease caused by protozoan infection), or
cytomegalavirus (a common type of herpes virus). A temporary form of
acquired Selective IgA Deficiency has been reported following treatment
with penicillamine for Wilson's Disease, which is an inherited disorder
caused by accumulation of copper in the body causing multiple symptoms,
or phenytoin/hydantoin (brand name: Dilantin) for seizure disorders.
However, when these drugs are withdrawn, the IgA deficiency is reveresed.
Signs and Symptoms
presentation of IgA deficient persons may range from healthy and symptom
free to significant illness. However, most people with this defect are
healthy and symptom free. No one knows why the course of Selective IgA
Deficiency is so varied. However, some IgA deficient persons with
significant illness may also be missing a fraction of their IgG (IgG2),
a class of immunoglobulin that offers protection against some kinds of
Thus, some IgA deficient persons may be totally unaware of their
antibody deficiency with no more than the usual number of upper
respiratory infections and/or occasional diarrhea.
For those IgA deficient patients with a history of recurrent
infections, the most common presentation is ear infections, sinusitis,
and/or pneumonia Other infection sites can be the throat, the
gastrointestinal tract or the eyes. These infections may become chronic
and may not completely clear up with a course of antibiotics,
necessitating prolonged antibiotic therapy.
Allergies are another common presentation of Selective IgA
Deficiency, and also may be quite varied, ranging from mild to sever.
Common allergic reactions include asthma and food allergies. Asthma in
some IgA deficient patients may be severe and less responsive to drug
therapy. Food allergies may result in symptoms such as diarrhea or
abdominal cramps. A link between Selective IgA Deficiency and allergic
rhinitis or eczema is uncertain.
Another, more unusual form of allergy that occurs in persons who have
a total absence of IgA is an allergic reaction to IgA. Exposure through
blood products containing IgA causes some IgA deficient individuals to
develop antibodies against this foreign protein. In some cases, no
previous exposure to blood or blood products is known but such an
antibody appears anyway. If an anti-IgA antibody develops, a massive
allergic reaction can result during blood or plasma transfusions. If
possible, IgA deficient persons who need blood should be tested for
autoantibodies (antibodies to the body's own tissues) to IgA before
receiving blood products containing IgA. If autoantibodies exist, the
IgA deficient person could receive washed red blood cells, or blood
products from another blood type matched IgA deficient donor or from an
autologous (from one's own body) blood donation.
The incidence of autoantibodies (antibodies to the body's own tissue)
in IgA deficiency are believed to be high, possibly as high as 40%.
These autoantibodies may be directed against IgG, smooth muscle,
mitochondria (portion of a cell that is its energy source), basement
membrane (thin layer under mucous membrane composed of collagen),
desoxynucleoprotien (DNA)(portion of the cell that carries genetic
information), thyroglobulin (protein from thyroid gland) and parietal
cells (cells in the wall of the stomach). However, the presence of such
antibodies is not necessarily associated with disease.
Autoimmune diseases (immune system mistakenly attacks the body's own
tissues) comprise the third common clinical presentation of persons with
Selective IgA Deficiency. Autoimmune diseases occur in Selective IgA
Deficiency when patients produce antibodies to their own tissues,
damaging some of their organs or tissues. Autoimmune diseases most
frequently associated with Selective IgA Deficiency include rheumatoid
arthritis, systemic lupus erythematosus and Sjögren's Syndrome (a
syndrome more common in women, characterized by decreased lacrimal and
salivary gland secretion). These diseases may present as sore and
swollen joints of the hands or knees, a facial rash, anemia (decreased
red blood cells or hemoglobin), or abnormally low platelet count.
Other autoimmune diseases associated with Selective IgA Deficiency
affect the endocrine system, blood forming organs, or the
gastrointestinal system. These include thyroiditis (inflammation of the
thyroid gland), hemolytic anemia (anemia caused by increased red blood
cell destruction), and chronic active hepatitis (chronic inflammation of
Diseases and genetic disorders reported to be associated with
Selective IgA Deficiency include:
Relation to patient with hypogammaglobulinemia
Celiac disease (an intestinal malabsorption syndrome
characterized by diarrhea, malnutrition, and low calcium levels)
Endocrinopathy (any disease caused by disorder of the endocrine
Hyersplenism (an increased spleen activity causing anemia,
increased red blood cell destruction, and spleen enlargement) and
thrombocytopenia (abnormally low platelet count)
Intestinal nodular hyperplasia (excessive formation of intestinal
Recurrent giardiasis (protozoan infection)
Pulmonary hemosiderosis (deposits of iron-containing pigment from
hemoglobin in lungs due to red blood cell destruction)
Autoimmune diseases associated with Selective IgA Deficiency include:
Rheumatoid arthritis (chronic inflammatory disease causing joint
changes and deformities)
Juvenile rheumatoid arthritis (rheumatoid arthritis affecting
juveniles with onset before 16; remission occurs in 75% of patients)
Systemic lupus erythematosus (chronic inflammation of connective
tissues affecting skin, joints, kidneys, and nervous system)
Thyroiditis (inflammation of the thyroid gland)
Pernicious anemia (anemia due to low intestinal absorption of
Dermatomyositis (connective tissue disease with edema, dermtitis,
and muscle inflammation)
Coomb's positive hemolytic anemia (positive for antibodies to part
of red blood cell causing anemia due to red blood cell destruction)
Idiopathic Addison's disease (deficiency of secretions of
adrenocortical hormones from the adrenal gland which affects almost
all body systems)
Sjögren's Syndrome (syndrome more common in women characterized by
decreased lacrimal and salivary gland secretion)
Cerebral vasculitis (inflammation of blood or lymph vessels of the
Idiopathic thrombocytopenic purpura (hemorrhagic disorder with
severe decrease of circulation platelets due to clumping of platelets)
Deficiency is usually first suspected because of a history of chronic or
recurrent infections, allergies, autoimmune diseases, or chronic
Confirmation of Selective IgA Deficiency is made though a laboratory
test which measures IgA levels in the blood or serum. In the IgA-deficient
patient, IgA levels will either be absent or below 7mg/dl, while other
classes of immunoglobulin are normal. In a small percentage of cases,
perhaps 10%, an IgA-deficient patient may also be deficient in IgG2.
T-cells, phagocytic cells, and the complement system are normal or near
Tests to further evaluate Selective IgA Deficiency include:
1.Tests to measure serum immunoglobulin concentrations, These
tests are performed by single radial diffusion, radioimmunoassay,
ELISA, or automated laser nephelometry.
2.Assessment of IgG2. These tests include radioimmunoassay, ELISA,
or other methods of measuring this fraction.
3.Assessment of antibody formation following immunization. These
may include assessment of antigens or actual immunizations followed by
such tests. IgA-deficient persons usually have normal antibody
response, but have a poor response to vaccines for certain bacterial
4.Tests that measure circulating B- and T-lymphocytes. These tests
are usually not necessary. However, if they are employed, their
purpose is to count B-lymphocytes by detection of membrane-bound
immunoglobulin or monoclonal antibodies to B-cell antigens using
immunofluorescence. T-lymphocytes can be counted by
immunofluorescence with monoclonal antibodies.
If the patient is systematic, other tests may include a complete
blood count, lung function test, urinalysis, thyroid and kidney
functions, tests of nutrient absorption in the intestinal tract, and
tests to assess the autoantibodies.
There is no
treatment for Selective IgA Deficiency. Instead, treatment should be
directed toward the specific disease associated with Selectuive IgA
Deficiency, if any.
For example, steroids or immunosuppressive treatment may be needed in
patients with systemic lupus erythematosus (chronic inflammation of
connective tissue, affecting skin, joints, kidneys and the nervous
system), autoimmune diseases (immune system mistakenly attacks body's
own tissues), or antibiotics for infections.
Gammaglobulin treatment is not used in IgA Deficiency unless IgG2
Subclass Deficiency and/or antibody deficiency is also present.
Commercial gammaglobulin preparations do not contain much IgA, and even
if IgA-rich preparations were produced, the infused IgA appears not to
go to the mucous membranes where this protein is needed. If anti-IgA
antibodies are known to be present, IgA depleted intravenous
immunoglobulin are available and safe (brand name: Gammagard SD and
Other treatments include the removal of gluten (the protein from
wheat and other grainsvegetable albumin) from the diet, which has been
found helpful in lessening severe gastrointestinal symptoms in children
or adults who have associated celiac disease (intestinal malabsorption
syndrome characterized by diarrhea, malnutrition, and low calcium
levels). Patients with giardia (a protozoan infection) should be
treated with metronidazole (brand name: Flagyl/Protostat) or quinacrine
hydrochloride (brand name: Atbrine).
with Selective IgA deficiency live their full life span without any
problems. The reason why some IgA deficient persons have problems is
not clear. The prognosis in these cases is the same as the prognosis
for the associated disorder (if any) they exhibit, such as asthma or
There is no
means of prevention of Selective IgA Deficiency. Because IgA Deficiency
does not become detectable until approximately six months of age,
prenatal and neonatal detection of this disorder is currently not
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