If the word immunodeficiency in this title rings a bell, it’s most likely because that word is the “I” in HIV and AIDS — the human immunodeficiency virus and the disease it causes, acquired immunodeficiency syndrome.
But immunodeficiency isn’t only acquired. In fact, often it is something you are born with. This is called primary immunodeficiency, or PID. “That means one or more components of the immune system is not working or defective,” says Dr. Mark Ballow, a professor of pediatrics in the division of allergy and immunology at the University of South Florida.
PID is an umbrella term for a conglomeration of comparatively rare genetic disorders. According to the Immune Deficiency Foundation, PID has been diagnosed in about 250,000 people in the U.S. Thus, though rare, PID diseases are more common than better known genetic disorders such as hemophilia (less than 15,000), cystic fibrosis (30,000) and Huntington’s disease (30,000), the IDF says.
So far, well over 400 genetic mutations have been identified as causing disruptions in the immune system. Most are inherited from one or both parents, but some occur during gestation. “In the majority of patients, symptoms occur in the first year of life. This is called severe combined immunodeficiency, or SCID. But some begin in their 30s, 40s and 50s,” Ballow says. “So far, we have identified only about 35% of gene abnormalities in late-onset PID, so we have a long way to go in understanding what causes this particular immune deficiency.”
Symptoms and Types of PID
The Mayo Clinic says those with PID develop infections more frequently, and these infections are longer lasting or are harder to treat than in those with a normally functioning immune system. PID patients may also get unusual infections that a healthy immune system normally fights off, known as opportunistic infections.
Signs and symptoms differ depending on the type of primary immunodeficiency disorder, and they vary from person to person, the Mayo Clinic says, but may include:
— Inflammation and infection of internal organs.
— Blood disorders, such as low platelet counts or anemia.
— Digestive problems, such as cramping, loss of appetite, nausea and diarrhea.
— Delayed growth and development.
These conditions can lead to serious complications, including:
— Damage to heart, lungs, nervous system or digestive tract.
— Increased risk of cancer.
— Death from serious infection.
With hundreds of PID disorders identified, physicians and researchers classify them into six groups, based on the part of the immune system that’s affected:
— B cell (antibody) deficiencies.
— T cell deficiencies.
— Combination B and T cell deficiencies.
— Defective phagocytes.
— Complement deficiencies.
— Unknown (idiopathic).
Treatments for PID depend on which of those six types of disorder the patient has. They can include preventing and treating infections, improving immune system function and treating the underlying cause of the disorder. For those with severe, life-threatening immunodeficiency, stem cell transplantation may be needed. When PID is linked to an associated disease such as an autoimmune disorder, heart disease or cancer, those of course need treatment as well.
Those with B cell antibody deficiencies also have the opportunity to have those antibodies replaced with an infusion of immunoglobulin, or IG. Immunoglobulin consists of antibody proteins needed for the immune system to fight infections. This product is made from the blood plasma donated by healthy individuals at the Red Cross and other blood donation sites.
This treatment has been around for a long time, says Dr. Kathleen Sullivan, chief of the division of allergy and immunology at Children’s Hospital of Philadelphia and a member of the Immune Deficiency Foundation’s Physicians Advisory Committee. It was first used in the 1950s, when physicians would give raw, untreated plasma to patients, with some success. “In the 1980s, companies developed purification strategies to deliver immunoglobulin in high doses intravenously,” she says.
IG infusions are also used in other PID conditions. “For pure antibody efficiency, you can do exceedingly well just by replacing what’s missing, but there are others who have more going on,” Sullivan says. These patients may require immune suppression for autoimmune disease, antibiotics and other treatments along with IG. “With so many different conditions, you can understand there is quite a spectrum of treatment options,” she says.
For years, this treatment was delivered through an IV line at an infusion center. “IV infusions deliver high doses of immunoglobulin, but they are also inconvenient,” Sullivan says. “It takes half a day, once a month. It can be lifesaving, but rather burdensome.” More recently, patients have been given the option of delivering the treatment themselves at home, subcutaneously, similar to an insulin shot, once or twice a week.
Ballow says that the choice of infusion or self-injection is up to the patient. “Some people want to stick out an arm and get an IV once a month. It may take two to four hours, but elderly patients are just as happy to go to an infusion center because time is not an element for them,” he says. However, “parents love the subcutaneous (approach). They can do it at home, and older kids do it themselves. We have a cream, a local anesthetic, that kids can rub on the skin so they don’t even feel the needle.”
Plasma Donations Are Needed
The U.S. is currently experiencing a “devastating” shortage of plasma, the American College of Allergy, Asthma and Immunology recently stated. And with COVID-19 causing many potential blood donors to stay home, Sullivan expects those shortages, and the supply of immunoglobulin, to grow worse in the coming year, because it takes that long to process and sterilize the plasma into a usable product. Not only that, it takes a lot of plasma — more than 130 plasma donations per year — to treat one patient with PID. The ACAAI says that between 10 and 40 plasma donations go into a single dose of immunoglobulin, and between 1,500 and 50,000 units of plasma go into a single batch.
Plasma donation is similar to giving blood, says the organization DonatingPlasma.org. A needle placed into a vein in your arm collects plasma through a process call plasmapheresis. It draws out whole blood, then separates the plasma from the red blood cells and other blood components. These are then returned to your body, along with a sterile saline solution that helps replace the liquid plasma removed from the whole blood. The process takes 90 minutes to two hours.
That would be time well spent. Plasma “is a bit of a miracle cure,” said Dr. J. Allen Meadows, president of the ACAAI, in a released statement. “Plasma donation is a gift of life.”
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Correction 08/07/20: A previous version of this story misstated the number of people diagnosed with primary immunodeficiency in the U.S.