Understanding Primary Immunodeficiency (PI)

Primary immunodeficiency, or PI, is a group of chronic disorders, including many rare diseases. These diseases are caused by problems in the immune system that are present at birth, although symptoms may not appear until later in life. Immunodeficiency means your immune system is not working correctly. PI is not something you catch from someone else. It is something you are born with.^1,2

Your immune system is your body's defense team. It protects you from germs like bacteria, viruses, and fungi. When your immune system works well, it fights off infections. If you have PI, your immune system cannot fight off infections as it should. This can lead to frequent or severe infections.^1,2

There are more than 400 different types of PI. Each type affects the immune system differently. Some types make it hard for your body to make antibodies. Antibodies are special proteins that fight germs. Some types might affect your white blood cells. White blood cells are also very important for fighting infections.^1-3

What causes primary immunodeficiency?

PI is caused by changes in your genes. Genes are like instruction manuals for your body. If there is a mistake in a gene that controls your immune system, it can lead to primary immunodeficiency.^1,2

These genetic changes can be inherited from your parents. This means they are passed down through families. But PI is not always inherited. Sometimes, the genetic change happens for the first time in a person.^1,2

How does PI affect people?

The impact of PI can be different for everyone. It depends on the type of PI and how severe it is.^1,2

One common problem for people with PI is getting infections often. These infections can be in different parts of the body. You might get ear infections, sinus infections, or pneumonia. These infections might be more severe or last longer than usual. They might also be harder to treat with regular medicine.^1,2

Other signs and symptoms of PI include:^1,2,4

• Needing antibiotics longer than usual
• Enlarged or affected lymph nodes, spleen, or liver
• Failure to thrive (in infants)
• Unexplained weight loss
• Frequent diarrhea or stomach issues

Besides infections, PI can also cause other health issues. Your immune system might mistakenly attack healthy parts of your body. This is called autoimmunity. It can lead to problems like arthritis or digestive issues. Some people with PI might also have a higher risk of certain cancers. These other problems show how PI can affect the whole body, not just its ability to fight infections.^1-3

Types of primary immunodeficiency

As mentioned, there are many types of PI. They are grouped based on which part of the immune system is affected.^1-3

One common group is antibody deficiencies involving problems with B-cells, a type of white blood cell that helps make antibodies. In these types, the body does not make enough antibodies, or the antibodies do not work well. Common variable immunodeficiency (CVID) is a well-known example. People with CVID often have low levels of important antibodies, making them prone to bacterial infections.^3,5

Another group involves problems with T-cells. T-cells are a type of white blood cell that helps fight viruses and other germs.³

Another group affects both B-cells and T-cells. Severe combined immunodeficiency (SCID) is a very serious type of PI affecting both of these cells important to the immune system. Babies with SCID have almost no working immune system. They need very special care and treatment to survive.^3,6

There are also PIs that affect phagocytes (immune cells that "eat" and destroy certain germs). Chronic granulomatous disease (CGD) is an example. People with CGD have trouble killing certain types of bacteria and fungi, which can lead to severe infections and inflammation.⁷

Other types of PI affect different parts of the immune system. Some affect the complement system, which is a group of proteins that help fight infections. Others affect natural killer cells, which are important for fighting viruses and cancer cells. The variety of PI types highlights the complex nature of the immune system.^1-3

Treating primary immunodeficiency

Treating PI can be a lifelong journey. The main goals are to prevent and fight infections, help the immune system work better, and, in some cases, address the underlying problem. The specific treatment depends on the type of PI a person has.^1,2
Treatment strategies for PI may include:^1,2,8

• Preventing and treating infections – This can include good hygiene practices, antibiotics, antivirals, and antifungals.
• Intravenous immunoglobulin (IVIG) – This involves giving antibodies directly into a vein. These antibodies come from healthy donors and help replace the missing or poorly working antibodies in people with certain types of PI.
• Stem cell transplantation – Also known as a bone marrow transplant, this can offer a cure for some severe types of PI. It involves replacing the person's faulty immune system cells with healthy ones from a donor. This is a complex procedure with risks, but it can create a new, functioning immune system.
• Gene therapy – This is a newer and advancing treatment approach. It involves taking a person's own stem cells, correcting the faulty gene that causes PI, and then putting the corrected cells back into the person's body. Gene therapy aims to fix the underlying genetic problem, allowing the body to make its own healthy immune cells. This is currently available for only some types of PI through clinical trials.

Living with primary immunodeficiency

Living with primary immunodeficiency can be challenging. It often requires ongoing medical care. This can include taking medicines to prevent infections. Some people may need regular IVIG infusions. This treatment helps replace the missing antibodies in their body.^1,2,8,9

Early diagnosis of PI is important. It helps people get the right treatment sooner. This can help prevent serious infections and other health problems. Doctors use different tests to diagnose PI. These tests can inform how well the immune system is working.¹

There is hope for better ways to manage these conditions. Organizations and support groups are also available to help those with PI and their families. They provide information, support, and a sense of community. Understanding PI is the first step toward managing it effectively and living a full life.⁹