Immunoglobulins, commonly known as antibodies, are specialized proteins produced by the immune system that circulate in the blood and bodily fluids to neutralize threats like viruses and bacteria. Immunoglobulin G (IgG) is the most abundant of these protective molecules, making up approximately 75% of the total antibodies in the bloodstream. An IgG deficiency occurs when the body fails to produce sufficient levels of these functional antibodies, leading to a compromised ability to fight off infections. This deficiency can arise as a primary immune disorder, often due to genetic factors, or it can be a secondary condition resulting from underlying diseases or certain medical treatments.
The Role of Immunoglobulin G
IgG serves as the immune system’s long-term memory, responsible for the secondary immune response that rapidly eliminates previously encountered pathogens. These antibodies work by coating the surface of foreign invaders (opsonization), which signals specialized white blood cells to engulf and destroy the microbe. IgG molecules also directly neutralize toxins and viruses by binding to them, preventing them from entering host cells.
The molecule’s structure allows it to easily diffuse into tissues and extracellular spaces, providing broad protection throughout the body. IgG is also the only antibody capable of crossing the placenta from mother to fetus, granting temporary passive immunity to newborns during their first months of life. A deficiency compromises the body’s sustained defense, especially against encapsulated bacteria like Streptococcus pneumoniae and Haemophilus influenzae.
Recognizing the Signs of Low IgG
The clinical presentation of low IgG levels centers on recurrent, persistent, or unusually severe infections, particularly within the respiratory tract. Patients commonly experience repeated episodes of sinusitis, otitis media, and bronchitis that require frequent courses of antibiotics. These infections often fail to clear completely or return quickly after treatment, indicating a failure of the immune response to establish lasting protection.
Over time, chronic inflammation and repeated infection can lead to permanent structural damage in the lungs, such as bronchiectasis. This damage further impairs breathing and increases the risk of future infections. The body’s inability to mount a proper defense means that standard vaccinations may not be effective, as the production of protective antibodies is impaired.
Identifying the Cause and Confirmation
The first step in diagnosis involves a blood test to measure the total serum IgG level, along with other major immunoglobulins like IgA and IgM. A low total IgG concentration suggests hypogammaglobulinemia, which may indicate a primary immunodeficiency like Common Variable Immunodeficiency (CVID). Secondary causes, which are more common, must also be investigated, including immunosuppressive drugs, certain cancers, or significant protein loss due to kidney or gastrointestinal disorders.
Confirmation of a true functional deficiency requires a specific antibody response test, often called a vaccine challenge. This test is necessary because some individuals have normal total IgG levels but cannot produce protective antibodies against specific pathogens, a condition known as Specific Antibody Deficiency (SAD). The patient receives a vaccine, typically against pneumococcus, and the immune response is measured several weeks later to determine if they successfully generated a protective antibody level. Failure to respond adequately confirms the diagnosis of an antibody deficiency.
Treatment Options for Deficiency
The management for IgG deficiency is Immunoglobulin Replacement Therapy (IRT), which provides missing functional antibodies pooled from the plasma of healthy donors. IRT supplements the body’s defenses to prevent serious and recurrent infections. The two main delivery methods are Intravenous Immunoglobulin (IVIg) and Subcutaneous Immunoglobulin (SCIg).
Intravenous Immunoglobulin (IVIg)
IVIg is administered directly into a vein, usually in a clinical setting, every three to four weeks. This schedule results in high peak IgG levels immediately after infusion and lower trough levels before the next dose. This fluctuation can sometimes lead to systemic side effects like headache or fatigue.
Subcutaneous Immunoglobulin (SCIg)
SCIg is infused under the skin, often weekly at home. This method maintains a much steadier IgG level in the bloodstream and minimizes the fluctuation associated with IVIg. The goal of both therapies is to maintain a protective trough IgG level, often targeted above 600 mg/dL, which is associated with a lower rate of severe infections. Prophylactic antibiotics may also be prescribed as an additional measure to manage breakthrough infections.