Immunoglobulin Replacement Therapy for Primary Immunodeficiency: How It Works, Side Effects, and More

Immunoglobulin replacement therapy is a lifesaving treatment for people with some types of primary immunodeficiency (PI). This treatment helps prevent recurrent infections and improve quality of life in people who can’t make their own antibodies. Most people who need immunoglobulin replacement therapy continue treatment for the rest of their lives.

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In this article, we’ll explore how immunoglobulin replacement therapy works, the different types of treatment, and their side effects so that you feel prepared to discuss treatment options with your healthcare team.

What Is Immunoglobulin Replacement Therapy?

Immunoglobulin replacement therapy is a treatment that provides your body with antibodies it can’t make on its own. Antibodies are immune proteins made by B cells (a type of white blood cell). When a foreign substance (like a bacterium, virus, parasite, fungus, or toxin) enters your body, antibodies recognize it as a threat and attach to it in order to neutralize it. Antibodies send signals that instruct the immune system to destroy the harmful substance.

Immunoglobulin (Ig) is another name for antibody, so you can think of immunoglobulin replacement therapy as antibody replacement therapy.

Who Needs Immunoglobulin Replacement Therapy?

Ig replacement therapy is the standard treatment for people with PI who don’t make antibodies of their own or whose antibodies don’t work well — a condition known as an antibody deficiency. Specialists from the American Academy of Allergy, Asthma & Immunology recommend regular Ig replacement therapy for people who have a PI that causes antibody deficiency. Ig therapy is also approved by the U.S. Food and Drug Administration (FDA) for this purpose.

Ig replacement therapy is indicated for several types of PI, including:

• Common variable immunodeficiency (CVID)
• X-linked agammaglobulinemia (XLA)
• Autosomal recessive agammaglobulinemia (ARA)
• Hyper-IgM syndromes

This treatment can also benefit people with other types of primary antibody deficiencies, such as selective IgA deficiency, selective IgM deficiency, and specific antibody deficiency.

How Does Immunoglobulin Replacement Therapy Prevent Infections?

People with a type of primary immunodeficiency that causes antibody deficiency don’t have enough working antibodies to protect them from infection. Immunoglobulin replacement therapy provides ready-made, working antibodies so that your body doesn’t have to produce them on its own.

The antibodies in Ig replacement therapy come from donated human plasma (the liquid part of blood that contains antibodies). There are several types of immunoglobulin products, each with a different brand name. Each is made from about 10,000 donors to make sure there’s a broad spectrum of antibodies to cover a wide variety of germs. The donors and the donated plasma are tested for infectious diseases several times to make sure this process is safe.

Between 95 percent and 98 percent of the antibodies in Ig replacement therapy are IgG. This antibody is the most common type of antibody. Its main function is to protect you from bacteria and viruses. There can also be a small amount of other antibody types, including IgA and IgM.

After you receive Ig therapy, the antibodies can give you extra protection for about one to four weeks. After this time, antibody levels begin to drop and the dose needs to be repeated for continued protection. This treatment only temporarily replaces missing antibodies. It doesn’t prompt your body to make its own antibodies.

It’s important to know that Ig replacement therapy won’t prevent all infections. However, this treatment can help reduce the frequency and severity of infections.

What To Expect Before Starting Immunoglobulin Replacement Therapy

Immunoglobulin replacement therapy isn’t a temporary solution — it’s a lifelong treatment. In most cases, once you have a diagnosis that causes antibody deficiency, you’ll need Ig replacement for the rest of your life.

Testing Before Treatment

Before you start Ig replacement therapy, your healthcare provider will run several immune studies. These tests can help confirm that your body doesn’t just have low antibody levels, but that it can’t produce antibodies.

These tests often involve measuring your antibody levels before and after you get a vaccine, such as the pneumococcal vaccine. This test can show how well your immune system is able to make antibodies.

Immune studies must be done before Ig replacement therapy begins. Once this treatment begins, it’s not possible to get accurate results from these tests without stopping treatment.

Finding the Right Dose

You’ll work with your immunologist to find the right dose for you. Most people start with a dose based on their weight. Your individual dose may change based on blood test results, your doctor’s judgment, and how you respond to treatment. The goal is to keep a steady amount of Ig in your blood to balance infection prevention with the risk of side effects.

How Is Immunoglobulin Replacement Therapy Given?

There are two main ways Ig replacement therapy is given: intravenously (into a vein) and subcutaneously (under the skin). Both methods are equally effective, but there are pros and cons to each. About half of people getting Ig therapy get their therapy intravenously, while the other half receive subcutaneous Ig treatment. Your healthcare provider can help you understand the risks and benefits of each type of Ig replacement therapy to find the best fit for your individual needs.

Intravenous Immunoglobulin Replacement Therapy

Intravenous Ig therapy — often referred to as IVIG — is given as an infusion directly into your vein. IVIG is given by a healthcare professional in a hospital or infusion center, or sometimes at home. Most people need IVIG every three to four weeks. Each IVIG infusion takes two to six hours, depending on your dose and how you tolerate it.

Subcutaneous Immunoglobulin Replacement Therapy

Subcutaneous Ig therapy — often referred to as SCIG — is given as an injection or infusion under the skin, usually in the belly, arms, or thighs. After proper training, you can give yourself the SCIG injection at home. SCIG is usually given more often than IVIG, from once daily to once every two weeks.

For people who want less frequent dosing, facilitated SCIG may be an option. In facilitated SCIG, healthcare providers give hyaluronidase along with the Ig replacement therapy. Hyaluronidase is a natural protein found under the skin that allows healthcare providers to inject a larger volume at one time. Facilitated SCIG is often given by a healthcare provider every three to four weeks.

What Are the Side Effects of Immunoglobulin Replacement Therapy?

Adverse reactions (side effects) are more common in IVIG therapy than they are in SCIG therapy. With IVIG, most side effects are related to an infusion rate that’s too fast or the wrong temperature. Common infusion reactions with IVIG include:

• Headache
• Nausea and vomiting
• Fever and chills
• Flushing
• Backache
• Joint or muscle pain
• Chest tightness
• Wheezing

IVIG side effects are more likely in certain circumstances, including:

• During the first few treatments
• When you’re switching products
• If you have an underlying condition
• When you’re sick

In most cases, slowing down the infusion rate reduces side effects. Staying hydrated can also help prevent rare but serious side effects like an increased risk of blood clots and aseptic meningitis.

If side effects don’t improve, it may help to switch to another brand of IVIG. Your healthcare provider can also prescribe medications, such as diphenhydramine, acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs) like aspirin or ibuprofen, and corticosteroids to help prevent side effects.

People who can’t tolerate IVIG may wish to switch to SCIG, which often has milder side effects. However, SCIG can cause side effects like discoloration, irritation, and swelling at the injection site.

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Have you had immunoglobulin replacement therapy? Did you experience any side effects? Share your experience in the comments below.