Primary Immunodeficiency (PI)

What is Primary Immunodeficiency (PI)?

Primary immunodeficiency refers to an immune system which from birth is either broken or completely missing. It is not a condition acquired after birth from infection or accident. It is a genetic malfunction, unique to an individual, and can affect just one cell or many parts of the immune system.

Each individual has his or her own blueprint, a map made up of millions of bits of information called genes. The gene-map of each individual is a unique mix of genes from the mother and father. This map instructs the body how to build and how to maintain itself. Sometimes there are malfunctions in this map. When it fails to produce a functioning immune system the disease resulting is called a primary immune deficiency (PI). Sometimes there may be a history of such a malfunction in the family, but often there is not.  It all depends upon how the genes of the parents have come together to make up the blueprint for a unique and distinct individual.

There are more than 250 genetic defects and disorders of the immune system that are recognized as Primary Immunodeficiency. These forms range widely in severity and symptoms. On average 1 in every 1,200 individuals are affected by this disease and early diagnosis and treatment are vital in saving lives. Some disorders such as Selective IGA Deficiency can be quite common,  occurring in 1 in 300. Others such as Severe Combined Immune Deficiency (SCID), occur in 1 in 50,000 – 70,000.

Approximately 29,000 Canadians suffer from Primary Immunodeficiency. Over 70% are undiagnosed.

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What are some types of PI?

IgA deficiency is the most common form of PI. IgA is an immune-globulin found primarily in the saliva and other body fluids that guard the entrances into the body. People without sufficient IgA may suffer from allergies, colds, and respiratory infections. Usually the condition is not severe and many people do not have any symptoms at all. It seems those of European ancestry are the most affected group. Because this PI varies across racial and ethnic lines there are various estimates of how often it occurs, but the average seems to be 1 in every 600.

DiGeorge syndrome, also known as microdeletion 22q11 syndrome, is the absence of or a very small thymus gland. The thymus is the gland that matures T cells. The majority of people with DiGeorge syndrome develop fairly normal numbers of T and B lymphocytes over time. It is estimated this PI affects 1 in 4000.

Common Variable Immunodeficiency (CVID), also known as hypogammaglobulinemia, is a group of disorders characterized by impaired antibody responses. This PI is marked by lower blood levels of two immune-globulins, IgG and IgA, and in about half the cases, of a third immune-globulin, IgM. People with CVID do not make sufficient or effective antibodies to fight bacterial and viral infections. The most common symptoms initially are recurrent and difficult to clear infections of ear, nose, sinuses, bronchi and lungs. Serious and even life-threatening infections are an issue, as is organ damage from recurrent infection, especially in the lungs, and bone abscesses. Some may be unable to produce or maintain antibody responses to vaccinations. CVID affects males and females in equal number. Some display symptoms early in life, and some not until their twenties or later. “Variable” refers to the fact that CVID can present in many ways and there is a wide range in severity. It is estimated this PI affects 1 in 10,000.

X-Linked Agammaglobulinemia is a PI affecting males. It is a blockage of the ability to produce B cells. Infections of the gastrointestinal tract, lungs, skin, or upper respiratory tract are common symptoms of this PI. It is estimated this PI affects 1 in 50,000.

Severe Combined Immunodeficiency (SCID), also known as “bubble boy disease”, is a rare, but most serious group of immune disorders in which both B and T cells are lacking or non-functional. About 50% of infants with SCID have B-cells that just do not work. This makes fighting off any infection almost impossible. It is estimated this PI affects 1 in 50,000 to 70,000.

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How is PI diagnosed?

There are many variations in how PI presents due to the fact that the immune system can be broken in so many ways. There are warning signs of PI, such as recurrent infections (ear infections, pneumonia, bronchitis, sinusitis, skin infections).

For some the first infection will be serious and life-threatening, and a definite red flag that there may be a problem with the immune system. Some will suffer recurrent infections from infancy. However, some infants with PI will not show symptoms early on due to IgA received through breast milk from the mother or from antibodies that cross the placenta in the womb and remain in the infant’s body until 4-6 months of age when normal infants start to make their own antibodies. In some cases warning symptoms will not show up until much later in life, even as late as one’s forties or fifties.

Diagnosis begins with the understanding and recognition of the warning signs. Are there more infections than normal? Do infections recur after treatment with medications? Do infections not respond to usual medications? The infections involved differ for adults and children. All too often the significance of the warning signs is overlooked, sometimes because they may seem quite mild. Each infection may be treated as a stand-alone illness. Delay in diagnosis and treatment often carries serious health consequences such as the development of more serious infections, chronic illnesses, and even death.

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How is PI treated?

A patient with a PI will be treated for any current infection with specific antibiotics, anti-viral or antifungal medications. In some PIs, to prevent permanent organ damage from recurrent infections, low or moderate doses of antibiotics may be recommended.

Some patients will need more of a boost.  In cases where the patient is not producing a supply or adequate supply of antibodies, these antibodies can be received by injection. This injection can be made into a vein (intravenous immunoglobulin, IVIG) or under the skin (subcutaneous immunoglobulin, SCIG).

IVIG usually is scheduled every three to four weeks, and SCIG scheduled on  a daily to weekly basis. IVIG and SCIG provide the consistent level of needed antibodies. Once started, treatment is usually lifelong. The supply of these antibodies is coordinated by the Canadian Blood Services and Hema-Quebec. Plasma containing antibodies is separated from the blood, treated, condensed, screened, and prepared for the individual doses. One dose may be made up from the contributions of more than a couple hundred donors.

In the most severe cases, where the immune system is completely non-functional (SCID), and in other extreme cases, a bone marrow transplant may be required. Because a transplant requires a match, this process can take weeks or months. While awaiting the transplant the patient may be kept in reverse isolation and given preparatory treatment. In some cases chemotherapy is used to remove any remaining parts of the broken immune system. When an appropriate donor is found, the transplant is performed. The new marrow provides the patient a new and fully functioning immune system. In some cases there may be some side effects, and in some cases medication may be required to prevent the donor cells from attacking the recipient until the patient becomes tolerant.

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Individuals with a Primary Immunodeficiency should talk to their immunologists before receiving any vaccinations or injections. They could cause serious illness or death. Individuals with a Primary Immunodeficiency should not receive any live vaccinations including:

  • bacille-Calmette-Guerin (BCG)
  • chicken pox (varicella) vaccine
  • measles-mumps-rubella (MMR) vaccine
  • oral poliovirus vaccine
  • rotavirus vaccine
  • vaccine against tuberculosis (TB)
  • yellow fever vaccine

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