Immunoglobulin Replacement Therapy: Mechanisms, Efficacy, and Clinical Applications

Introduction

Immunoglobulins are also called antibodies. These are the proteins that make the immune system of the body. These antibodies help in fighting infections or harmful foreign substances in the body, such as viruses or bacteria. Immunoglobulin replacement therapy is blood-based therapy that contains antibodies that will help fight body infections. This therapy is recommended in patients with weak immune systems, for whom the immune system is not producing the disease-fighting antibodies. This can either be given intravenously or subcutaneously.

What Is Immunoglobulin Replacement Therapy?

Immunoglobulin (antibody) replacement therapy (IRT) is one of the most common and effective therapies used in patients with primary immunodeficiency (PID) disorders, also known as inborn errors of immunity (IEI). These patients have insufficient antibodies to fight the infections. In these disorders, patients have weak immune systems, leading to infections and other health complications more easily. Therefore, antibodies or immunoglobulins are provided to patients to deal with infections more easily and to prevent any further complications.

What Are Immunoglobulins?

Immunoglobulins are alternatively referred to as antibodies. These are formed in the body in response to an infection or vaccination. Whenever antibodies recognize a microorganism or a foreign substance, they get physically attached to it and start a chain reaction that eventually destroys the infection. Some of the functions performed by antibodies include:

• Stopping the infection by killing pathogens like bacteria or viruses.

• Flagging the foreign object so the immune cells can act on it.

• Activating various molecules in the body helps in eliminating the infection.

There are five major classes of antibodies, including IgG, IgA, IgM, IgD, and IgE. IgG further has four different subclasses: IgG1, IgG2, IgG3, and IgG4. IgA has two subclasses, IgA1 and IgA2.

Among all these classes, IgG can be used for therapeutic purposes, and immunoglobulin used for the treatment includes 95 to 98 percent pure IgG with a small amount of plasma proteins, including IgA and IgM.

• IgG - Immunoglobulin G is the main antibody present in the blood that binds to bacteria and toxins and plays an important role in the defense system. It is the only immunoglobulin that can pass through the placenta and protects the newborn.

• IgM - Immunoglobulin M is the initial immune defense system that helps in protecting the body.

• IgA - Immunoglobulin A is present in the nasal discharge and saliva and prevents bacterial invasion from mucous membranes. It is also present in breast milk and protects the gastrointestinal tract of newborns from infections.

• IgD - Immunoglobulin D is present on the surface of B cells and helps in the production of antibodies and the prevention of respiratory tract infections.

• IgE - Immunoglobulin E is believed to be involved in the allergic reaction and is related to the immune reaction to the parasites.

Who Needs Immunoglobulin Replacement Therapy?

Immunoglobulin (antibody) replacement therapy is primarily used in two situations.

• One reason is in cases where an individual’s body is not making enough antibodies, which is also called humoral immunodeficiency. Therefore, IRT provides extra antibodies that the body cannot make on its own. These antibodies may last for several weeks to months. Therefore, patients might have to take immunoglobulin replacement therapy regularly.

• The second reason might be in cases where the immune system starts attacking a certain type of cell in the body, seen commonly in autoimmune disorders, such as

1. Thrombocytopenia (destruction of the body’s blood platelets).

2. Autoimmune hemolytic anemia (destruction of the body’s red blood cells).

3. Guillain-Barré syndrome (a condition affecting the nerves that control the breathing).

Additionally, it has been found that IRT helps the immune system from destroying its body cells in these conditions.

What Is the Route of Administration?

Immunoglobulin replacement therapy is usually administered in two ways - intravenously (IVIG) or subcutaneously (SCIG). SCIG can be administered in two ways - conventional or facilitated. The details of these techniques are explained below -

1. Intravenous Immunoglobulin (IVIG)

• Frequency of Dosing - Every three to four weeks.

• IgG Level - Initially, it has a high concentration of IgG, which decreases slowly over 21 days.

• Access - Requires intravenous (IV - administered into a vein) access.

• Time of Infusion - Usually three to four hours.

• Side Effects -

1. Chills.

2. Rigors.

3. Blood pressure changes.

4. Nausea or vomiting.

• Pre-medication - Sometimes required.

2. Facilitated Subcutaneous Immunoglobulin (fSCIG)

• Frequency of Dosing - Every two, three, to four weeks.

• IgG Level - Initial high peak concentration can be seen around the fourth day of administration but is low as compared to IVIg and decreases slowly over 21 days.

• Access - Does not require IV access. An individual can administer the drug independently.

• Time of Infusion - Usually three to four hours (may vary).

• Side Effects - Can be seen but to a lesser extent than IVIG.

• Pre-medication - Sometimes required.

3. Conventional Subcutaneous Immunoglobulin

• Frequency of Dosing - Daily to every 14 days.

• IgG Level - There is no variation in IgG levels, and the concentration remains constant once a steady state is achieved.

• Access - Does not require IV access. An individual can administer the drug independently.

• Time of Infusion - Less than 30 minutes.

• Side Effects - This does not show any systemic side effects, but localized burning or itching is possible.

• Pre-medication - Not required.

How Are Immunoglobulins Made?

• In the case of immunoglobulin (antibody) replacement therapy, the immunoglobulins are purified from the plasma of a blood donor.

• Plasma is a liquid part of the blood that lacks blood cells but contains all the proteins and other constituents of whole blood.

• The plasma and blood (red blood cells) are separated when the donor blood is collected.

• After that, the plasma is processed in highly specialized and regulated facilities to produce immunoglobulins, which can then be administered to the patient.

What Are the Indications of Immunoglobulin Replacement Therapy?

Immunoglobulin replacement therapy is usually indicated in patients with deficient levels of antibodies that can be present at birth or due to genetic abnormalities. It can develop into serious conditions later in life, which can be due to certain factors like age, malnutrition, infections like HIV (human immunodeficiency virus), or chemotherapy. The patient may experience certain symptoms later in life that may become hard to manage, such as:

• Recurrent infections.

• Difficult in treating the infections.

• Delayed growth in children.

• Ear infections.

• Sinusitis (infection of sinuses).

• Digestive tract infections.

• Pneumonia (infection of the lungs).

• Diarrhea.

• Muscle cramps.

• Nausea and vomiting.

What Are the Side Effects of IRT?

Immunoglobulin replacement therapy usually is a well-tolerated therapy and does not involve any rare side effects. However, some side effects can occur, which include:

• Risk of blood-borne infections.

• Low-grade fevers or headaches.

• Allergic reactions (very rare).

Conclusion:

The goal of immunoglobulin replacement therapy is to protect against infections. It is a critical treatment in case of primary immunodeficiency disorders that affect the production of antibodies in the body. This therapy is widely used to protect against various conditions, and the indications of Ig therapy are steadily increasing.