Immunoglobulin G (IgG) is the most abundant type of antibody, accounting for about 75% of all antibodies circulating in the blood and other body fluids. This protein, made by the immune system, provides long-term protection against viruses, bacteria, and toxins encountered throughout life. Understanding these levels is important because they reflect the overall state of the immune system and its ability to fight off past invaders. The concentration of IgG is not static; it is subject to influences ranging from normal biological processes to underlying health conditions. This article explores the specific factors that cause IgG levels to fluctuate, whether temporarily or in a sustained manner.
The Primary Role of Immunoglobulin G
IgG provides the body’s long-term defense, known as immunological memory. When the immune system first encounters a pathogen, it produces other antibodies, but the sustained response relies on pathogen-specific IgG. This protein recognizes and neutralizes foreign invaders, preventing them from entering and damaging cells.
IgG also acts as a marker in a process called opsonization, coating pathogens to make them visible targets for immune cells like macrophages to engulf and destroy. Furthermore, IgG is the only antibody class capable of crossing the placenta, providing the newborn with passive immunity and temporary protection until the infant’s immune system matures. Its long half-life, averaging around 21 days, allows for prolonged, sustained protection in circulation.
Normal and Temporary Fluctuations
IgG levels naturally change throughout a lifetime due to normal physiological processes. The most significant age-dependent fluctuation occurs in infancy, beginning with high levels derived from maternal transfer across the placenta. After birth, this maternal IgG gradually breaks down, leading to a temporary decrease, or nadir, between three and six months of age as the infant begins to produce its own antibodies.
A temporary spike in IgG is observed following an acute infection or vaccination as the body mounts a specific immune response. During pregnancy, a decrease in maternal serum IgG levels is observed, largely due to the increase in the total volume of blood, which dilutes the antibody concentration. Minor fluctuations in IgG are also tied to the body’s natural circadian rhythm, although these daily changes are not considered clinically significant.
Causes of Sustained Low IgG Levels
A chronically low IgG level, termed hypogammaglobulinemia, compromises the ability to fight infection. This can arise from either primary (genetic) or secondary (acquired) causes. A primary cause is Common Variable Immunodeficiency (CVID), a genetic disorder that impairs the ability of B cells to mature into antibody-producing plasma cells.
Sustained low IgG levels often result from acquired secondary causes, such as the use of immunosuppressive medications. Drugs like rituximab, which targets B cells, suppress the production of new antibodies, leading to persistent hypogammaglobulinemia. Protein loss through the kidneys, such as in nephrotic syndrome, can also deplete IgG from the bloodstream. Furthermore, hematologic malignancies, including chronic lymphocytic leukemia (CLL), can interfere with the normal production of functional antibodies, resulting in a sustained reduction of circulating IgG.
Causes of Sustained High IgG Levels
Sustained elevation of IgG levels, or hypergammaglobulinemia, indicates chronic, ongoing stimulation of the immune system. This activation is triggered by underlying conditions. Chronic infections, particularly those that persist over long periods, such as viral infections like HIV or chronic hepatitis, force the immune system to continuously produce large amounts of antibodies.
Chronic immune stimulation also occurs in autoimmune disorders, where the body produces antibodies against its own tissues. Conditions like rheumatoid arthritis and systemic lupus erythematosus frequently present with elevated IgG. An extreme rise can signal a plasma cell disorder, known as a monoclonal gammopathy. This occurs when a single, abnormal clone of plasma cells proliferates, producing an excess of one specific type of IgG, characteristic of conditions like multiple myeloma. This monoclonal spike is distinct from the broader, polyclonal rise seen in chronic infections or autoimmune disease, which involves many different types of plasma cells.