Immunoglobulin G (IgG) is the most abundant and functionally important class of antibodies, playing a primary role in fighting off bacterial and viral threats. These proteins circulate throughout the blood and tissues, acting as the body’s defensive memory. A low level of this protective protein, called hypogammaglobulinemia, leaves the body vulnerable. The connection between low IgG and cancer is complex, involving a two-way relationship where malignancy can cause the deficiency, and the deficiency may influence cancer risk or progression.
Understanding Immunoglobulin G and Deficiency
Immunoglobulin G is the primary antibody of the secondary immune response, produced after the body has encountered a pathogen (e.g., through infection or vaccination). Making up about 75% of all circulating antibodies, IgG is a small molecule that easily exits the bloodstream to protect tissues. Its functions include neutralizing bacterial toxins and viruses, preventing them from damaging host cells.
IgG also functions as an “opsonin,” effectively coating and marking foreign invaders for destruction by specialized immune cells like macrophages and neutrophils. This tagging process significantly enhances the efficiency of the immune response. A person is diagnosed with IgG deficiency, or hypogammaglobulinemia, when the total amount of IgG in the serum falls below the established lower limit of the normal range.
Deficiencies in IgG are categorized based on their origin. Primary immunodeficiencies are rare, genetic conditions that impair immune system development. In the context of cancer, the most common form is secondary immunodeficiency, acquired later in life due to underlying diseases or treatments. This acquired form frequently complicates oncology care, directly impacting the patient’s ability to fight infections.
The Role of Humoral Immunity in Cancer Surveillance
The body maintains a constant process known as immune surveillance, where the immune system actively scans for and eliminates abnormal or potentially cancerous cells. This surveillance relies heavily on the adaptive immune system, of which IgG is a major component. Cancer cells often display unique proteins, called tumor antigens, which the immune system can recognize as foreign.
IgG antibodies specifically bind to these tumor antigens, effectively flagging the malignant cell for destruction. This initiates antibody-dependent cell-mediated cytotoxicity (ADCC), where Natural Killer (NK) cells bind to the IgG and release toxic substances to kill the cancer cell. IgG can also activate the complement cascade, which forms a membrane attack complex that punctures and destroys the tumor cell.
When IgG levels are low, this surveillance mechanism is compromised, hindering the immune system’s ability to identify and eliminate malignant cells. A deficiency reduces the “flags” available to mark tumor cells, potentially allowing them to evade detection and grow unchecked. Sufficient IgG is therefore a natural defense line against the development and spread of malignancy.
The Reciprocal Relationship Between Low IgG and Malignancy
The relationship between low IgG and cancer flows in both directions, involving both cause and effect. The most common scenario is that the malignancy or its treatment directly causes the drop in antibody levels, leading to a secondary immunodeficiency.
Cancer and Treatment Causing Secondary Deficiency
Certain hematologic cancers, particularly those involving B-cells and plasma cells (the cells responsible for producing antibodies), are inherently linked to hypogammaglobulinemia. Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), and certain Lymphomas can directly impair normal B-cell function, preventing them from producing effective IgG antibodies. In CLL, for example, malignant B-cells crowd out healthy cells, reducing the quantity and quality of circulating immunoglobulins.
Many cancer treatments intentionally suppress the immune system, causing an acquired deficiency. Chemotherapy agents kill rapidly dividing cells, including the healthy immune cells that produce antibodies. Targeted therapies, such as the monoclonal antibody Rituximab, specifically destroy B-cells, the precursor cells for plasma cells that secrete IgG. Hypogammaglobulinemia can develop in nearly 40% of patients treated with Rituximab, necessitating careful monitoring and long-term management.
Deficiency Predisposing to Cancer
While not a direct cause, unmanaged, long-term IgG deficiency can indirectly increase the risk for certain malignancies, most notably lymphomas. The chronic inability to clear infections leads to persistent inflammation, a known risk factor for cellular damage. Recurrent, severe bacterial infections in the lungs or gastrointestinal tract create an environment of continuous immune activation and cell turnover.
Additionally, some primary immunodeficiency syndromes featuring profound IgG deficiency are associated with an increased risk of developing lymphoproliferative disorders (conditions involving the uncontrolled production of lymphocytes). This suggests that when the immune system’s regulatory and surveillance mechanisms are broken, it can lead to unchecked growth of immune cells. Maintaining adequate IgG levels is therefore important for preventing infection and mitigating the risk of long-term malignancy associated with immune dysfunction.
Diagnosis and Management Strategies
Diagnosis of IgG deficiency in cancer patients is typically initiated by suspected impaired immune function, often prompted by recurrent or unusually severe infections. The condition is confirmed through a simple blood test that measures the serum levels of IgG, IgA, and IgM immunoglobulins. An IgG level significantly below the reference range indicates hypogammaglobulinemia, though intervention relies on the low level combined with a history of infections.
The primary clinical consequence of unmanaged IgG deficiency is increased susceptibility to severe, often sinopulmonary, bacterial infections caused by encapsulated organisms like Streptococcus pneumoniae. These infections can lead to serious complications, including pneumonia and sepsis, significantly impacting patient outcomes. Guidelines recommend intervention for patients with an IgG level below 4 g/L who also experience recurrent infections.
The standard treatment for severe or symptomatic IgG deficiency is Immunoglobulin Replacement Therapy (IgRT), which involves administering concentrated IgG antibodies derived from healthy human plasma. This therapy is prophylactic, aiming to prevent infections rather than treat the underlying cancer. IgRT can be given intravenously (IVIg) every three to four weeks or subcutaneously (SCIg), often administered weekly or bi-weekly at home. Both methods effectively reduce the frequency and severity of bacterial infections, improving patient safety and minimizing hospitalizations.