Immunoglobulins, commonly known as antibodies, are proteins produced by the immune system to identify and neutralize foreign threats like bacteria and viruses. Immunoglobulin G (IgG) is the most abundant class, representing approximately 75% of the total antibodies found in the bloodstream. Low IgG levels, known as hypogammaglobulinemia, impair the body’s ability to mount an effective defense against pathogens. This deficiency leaves an individual susceptible to recurrent and often severe infections.
The Role of Immunoglobulin G in Immunity
IgG is a Y-shaped protein structure that functions as the long-term defense memory of the immune system. It is the primary component of the secondary immune response, produced in large quantities after initial exposure or vaccination to provide sustained protection. Its small size allows it to easily diffuse out of the blood vessels and into the tissues, where most infections occur.
The antibody neutralizes threats by binding to bacterial toxins or viruses to render them harmless. IgG also employs opsonization, coating the surface of a pathogen to “mark” it for destruction and ingestion by phagocytic immune cells. Furthermore, IgG is the only antibody class capable of crossing the placenta, granting newborns passive immunity that protects them during the first few months of life.
Defining Low IgG and Clinical Manifestations
A diagnosis of low IgG, or hypogammaglobulinemia, is made when the total serum IgG concentration falls below the normal reference range for a patient’s age. Quantitative testing, typically performed using a technique like nephelometry, measures the total amount of IgG circulating in the blood. A reduction that falls more than two standard deviations below the mean for age-matched controls is generally considered diagnostic.
The primary manifestation of a deficiency is an increased frequency and severity of bacterial infections, particularly those caused by encapsulated bacteria such as Streptococcus pneumoniae. Patients often experience recurrent infections of the respiratory tract, including chronic sinusitis, otitis media (ear infections), and pneumonia. A poor or absent response to standard vaccinations is another hallmark of the condition.
Chronic inflammation and persistent infections can lead to permanent tissue damage, such as the development of bronchiectasis in the lungs. In adults, total IgG levels below 400 to 600 mg/dL are often associated with clinical symptoms. A low level in the presence of recurrent illness warrants further investigation into the underlying immune function.
Primary and Secondary Causes of IgG Deficiency
The underlying reasons for low IgG are categorized into primary (inherited) and secondary (acquired) immunodeficiencies. Primary immunodeficiencies are rare genetic conditions that directly impair the body’s ability to produce adequate antibodies. Common Variable Immunodeficiency (CVID) is a primary form characterized by low IgG, often alongside low IgA and IgM, and poor functional antibody responses to vaccines.
In CVID, the patient has a normal number of B-cells, but these cells fail to mature into functional plasma cells. Another primary condition is X-linked agammaglobulinemia (XLA), which results in a profound deficiency of all immunoglobulins and is marked by extremely low to absent circulating B-cells. These congenital conditions often present with recurrent infections starting in infancy or early childhood.
Secondary causes are far more common and develop as a consequence of external factors, underlying diseases, or medical treatments. Hematologic cancers, such as Chronic Lymphocytic Leukemia (CLL), often lead to hypogammaglobulinemia because malignant B-cells interfere with normal antibody production. This deficiency can affect up to 70% of CLL patients, increasing their risk of severe infection.
Protein-losing conditions affecting the kidneys or gastrointestinal tract are another secondary cause. Nephrotic syndrome, for instance, involves the loss of large amounts of protein, including IgG, through the urine. Specific medications, such as certain anti-seizure drugs or immunosuppressive therapies used for autoimmune diseases, can also suppress the immune system’s ability to generate sufficient IgG levels.
Treatment Strategies for Managing Low IgG
The goal of managing low IgG is to prevent the severe infections that result from the immune deficit. The standard intervention is Immunoglobulin Replacement Therapy (IRT), which involves infusing concentrated antibodies derived from healthy donors. This therapy directly substitutes the missing antibodies, providing passive immunity to the patient.
IRT can be administered intravenously (IVIG) or subcutaneously (SCIG). IVIG is typically given every three to four weeks in a clinic setting, resulting in peak and trough IgG levels in the blood. SCIG involves smaller, more frequent infusions, often administered weekly at home, which maintains more stable and consistent IgG levels.
The target for this therapy is to achieve a trough IgG level—the lowest concentration just before the next infusion—sufficient to minimize the number of infections, often aiming for levels above 500 mg/dL. For patients who continue to experience frequent infections despite IRT, or for those with milder deficiencies, prophylactic antibiotics may be prescribed. Antibiotic prophylaxis works to suppress specific bacterial populations, offering an additional layer of protection against respiratory infections.