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Primary Immunodeficiency Diseases

Incidence  |  Description  |  Symptoms  |  Diagnosis  |  Treatment  |  Prognosis  |  Prevention


Selective IgA Deficiency

Incidence

In general, 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.

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Disease Description

Selective 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 no 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, progressive disease.

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 reversed.

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Clinical Signs and Symptoms

Clinical 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 bacterial infections.

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 auto antibodies (antibodies to the body's own tissues) to IgA before receiving blood products containing IgA. If auto antibodies 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 auto antibodies (antibodies to the body's own tissue) in IgA deficiency are believed to be high, possibly as high as 40%. These auto antibodies 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 the liver).

Diseases and genetic disorders reported to be associated with Selective IgA Deficiency include:

  • Allergic disorders
  • Recurrent infections
  • Asthma
  • Food Allergies
  • Crohn's Disease
  • Relation to patient with hypogammaglobulinemia
  • Celiac disease (an intestinal malabsorption syndrome characterized by diarrhea, malnutrition, and low calcium levels)
  • Chromosomal abnormality
  • Possible malignancy
  • Endocrinopathy (any disease caused by disorder of the endocrine glands)
  • 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 nodes)
  • 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)
  • Transfusion reaction
  • Pernicious anemia (anemia due to low intestinal absorption of vitamin B12)
  • Dermatomyositis (connective tissue disease with edema, dermatitis, 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 brain—cerebrum)
  • Idiopathic thrombocytopenic purpura (hemorrhagic disorder with severe decrease of circulation platelets due to clumping of platelets)

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Diagnosis

IgA Deficiency is usually first suspected because of a history of chronic or recurrent infections, allergies, autoimmune diseases, or chronic diarrhea.

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 normal.

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 pathogens.

  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 auto antibodies.

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Treatment

There is no treatment for Selective IgA Deficiency. Instead, treatment should be directed toward the specific disease associated with Selective 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 Polygam SD).

Other treatments include the removal of gluten (the protein from wheat and other grains—vegetable 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).

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Prognosis

Many persons 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 rheumatoid arthritis.

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Prevention

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 possible.

If you or your physician would like additional information on this disease please click here.

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Disclaimer: The information contained on these pages is not intended to provide specific medical advice; rather it is intended for informational purposes only, in order to provide a better understanding of these diseases. Please consult with a qualified physician for diagnosis and answers to your questions.

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