What is the effect of low immunoglobulins (Ig)?

From the Guidelines

Low immunoglobulins significantly increase the risk of severe and recurrent infections, and immunoglobulin replacement therapy (IgRT) is recommended for patients with hypogammaglobulinemia and a history of severe or repeated infections. When immunoglobulin levels are below normal, the body cannot adequately recognize and neutralize pathogens like bacteria, viruses, and fungi, making individuals more susceptible to frequent, severe, or persistent infections. This condition, known as hypogammaglobulinemia or antibody deficiency, can be primary (genetic) or secondary (acquired from medications, malnutrition, or other diseases) 1. Common symptoms include recurrent respiratory infections, gastrointestinal problems, and poor response to vaccines.

Causes and Risk Factors

The risk of hypogammaglobulinemia is increased in patients with chronic lymphocytic leukemia (CLL) treated with BTK and BCL-2 inhibitors 1. A multicenter retrospective study from Germany reported that the introduction of IgRT significantly reduced the risk of severe infectious complications in hematologic patients, including those receiving BTK-I for CLL (HR: 0.47; p = 0.003) 1.

Treatment and Management

Treatment typically involves immunoglobulin replacement therapy, administered intravenously (IVIG) or subcutaneously (SCIG), usually at doses of 400-600 mg/kg every 3-4 weeks for IVIG or weekly smaller doses for SCIG 1. The goal of therapy should be to improve clinical outcomes, rather than aiming for a specific trough concentration 1. A recent study suggested that a target trough of 600–800 mg/dL can improve clinical outcomes 1. Subcutaneous immunoglobulin therapy (SCIg) has been shown to be effective in increasing IgG levels and reducing infectious episodes 1.

Key Considerations

• Patients with hypogammaglobulinemia should be monitored for serum immunoglobulin levels and receive IgRT as needed 1.
• The optimal timing, preferred route of administration, dosing, frequency of administration, and duration of IgRT should be individualized based on patient needs and response to therapy 1.
• Patients should practice good hygiene, avoid close contact with sick individuals, and seek prompt medical attention for infections, as these can become serious more quickly than in people with normal immune function.

From the Research

Effects of Low Immunoglobulins (Ig)

• Low levels of immunoglobulins (Ig) can significantly increase the risk of infection, particularly respiratory tract infections of bacterial origin 2.
• Sustained, very low levels of IgA, IgG, or IgM are associated with increased risks of infections, with IgG levels <100 mg/dL or IgM levels <20 mg/dL posing a significant risk 2.
• Patients with low IgG levels may require replenishment to reduce the infection risk to background levels, with a target IgG level of approximately 500 mg/dL 2.
• The use of intravenous immunoglobulin (IVIG) therapy can help raise trough IgG levels and prevent severe and lower respiratory tract infections in patients with common variable immune deficiency 3.
• Low-dose IVIG therapy (200 mg/kg every 3 weeks) may not be sufficient to prevent infections, and standard-dose therapy (400 mg/kg every 3 weeks) may be more effective 3.

Immunoglobulin Replacement Therapy

• IVIG has been used as antibody replacement therapy in primary immunodeficiency diseases (PIDDs) for over 50 years 4.
• Replacement doses of IVIG are given on a monthly basis as a prophylactic measure to prevent acute and serious bacterial infections in PIDDs 4.
• IVIG can also be used as an immunomodulatory agent in autoimmune and inflammatory disorders, with mechanisms of action involving Fc-dependent and/or F(ab')2-dependent nonexclusive mechanisms 5.

Safety and Tolerability of IVIG

• Rapid infusions of human normal immunoglobulin 50g/l are safe and well tolerated in immunodeficiencies and immune thrombocytopenia 6.
• Adverse reactions to IVIG are usually mild, comprising transient flu-like symptoms, change in blood pressure, and tachycardia 6.
• High intravenous infusion rates of IVIG can be tolerated by patients with immunodeficiencies and immune thrombocytopenia, minimizing the time spent in outpatient hospital visits 6.