Immunoglobulins, commonly known as antibodies, are Y-shaped proteins that circulate through the blood and lymph, serving as the body’s primary defense against pathogens like bacteria and viruses. The most abundant type is Immunoglobulin G (IgG), which plays a sustained role in immune memory. An IgG Subclasses 1-4 test is a specialized blood examination that measures the precise concentration of the four distinct subtypes of this major antibody: IgG1, IgG2, IgG3, and IgG4. This measurement provides a detailed view of the immune system’s ability to mount a defense against various infections.
Defining Immunoglobulin G and Its Role
Immunoglobulin G constitutes approximately 75% of all antibodies found in the blood, making it the dominant component of the humoral immune system. It is the primary force behind the body’s secondary, or memory, immune response, providing long-lasting protection after exposure to a microbe or vaccine.
IgG can actively cross the placenta from mother to fetus during pregnancy. This transfer provides the newborn with temporary, passive immunity against infectious agents while the infant’s own immune system matures. IgG defends the body by coating pathogens to neutralize toxins and viruses. It also facilitates phagocytosis, where immune cells consume and destroy invaders, and activates the complement system, which directly bursts bacteria.
The Four Distinct Functions of IgG Subclasses
The four subclasses of IgG, while structurally similar, each specialize in combating different types of antigens, offering a layered defense.
IgG1
IgG1 is the most prevalent subclass, making up 60% to 70% of the total circulating IgG. It is primarily responsible for neutralizing toxins and is highly effective against protein antigens found on most viruses and bacteria.
IgG2
IgG2 accounts for 20% to 30% of total IgG. This subclass is specialized in responding to polysaccharide (complex sugar) antigens, which are characteristic of the capsules surrounding certain bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae.
IgG3
IgG3 is a less abundant subclass, representing 5% to 8% of the total. It is known for its high potency in activating the complement system and is effective against various protein antigens and viruses. However, it has a significantly shorter half-life in the bloodstream compared to the other subclasses.
IgG4
IgG4 is the least concentrated subclass, typically comprising only 1% to 3% of the total IgG. IgG4 is often associated with long-term, chronic exposure to an antigen and plays a role in certain allergic responses. It is also involved in a distinct set of autoimmune conditions.
Clinical Indications for Subclass Testing
Physicians order this specialized test when there is a suspicion of an underlying antibody deficiency, particularly a Primary Immunodeficiency (PID). The main indication is a history of recurrent or severe bacterial infections. These infections frequently involve the respiratory tract, presenting as chronic or repeated ear infections, sinusitis, bronchitis, or pneumonia.
The test is also prompted by a poor response to standard vaccinations, suggesting an inability to generate a proper immune memory response. Other clinical clues include chronic diarrhea, which points to gastrointestinal involvement, or a family history of immunodeficiency disorders. Measuring the subclasses is useful when the total IgG level appears normal, yet the patient continues to experience frequent infections.
Interpreting Results and Associated Conditions
A selective IgG subclass deficiency is diagnosed when the total IgG level is normal, but the concentration of one or more specific subclasses is persistently low. IgG2 and IgG3 deficiencies are the most frequently observed among symptomatic patients. A low IgG2 level, often with or without low IgG4, is commonly associated with recurrent infections caused by encapsulated bacteria.
A deficiency in IgG2 or IgG4 can indicate a poor ability to produce functional antibodies against polysaccharide vaccines, such as those for pneumococcus. Because IgG1 is the most dominant subclass, a significant deficiency in IgG1 will often cause the total IgG to drop below the normal range, a condition known as hypogammaglobulinemia. Management of a clinically significant deficiency may involve prophylactic antibiotics to prevent infections or, in cases of severe, persistent infections, Immunoglobulin Replacement Therapy. Treatment is based on the particular subclass involved, the severity of the patient’s symptoms, and the demonstrated failure to respond to vaccines.