What is the half-life of Immunoglobulin G (IgG)?

The Half-Life of IgG

The half-life of IgG is approximately 21 days for IgG1, IgG2, and IgG4 subclasses, while IgG3 has a shorter half-life of approximately 7 days. 1

IgG Half-Life by Subclass

• IgG1, IgG2, and IgG4 have similar half-lives of approximately 21 days in individuals with normal IgG serum concentrations 1
• IgG3 has a significantly shorter half-life of only 7.1 days 1
• These differences in half-life are inherent properties of the molecules and not due to denaturation during isolation or labeling processes 1

Factors Affecting IgG Half-Life

• Elevated serum concentration of any IgG subclass is associated with shortened biologic half-life and increased fractional catabolic rate of all subclasses 1
• The fractional catabolic rates of IgG1, IgG2, and IgG4 are approximately 6.9-8% of the intravascular pool per day 1
• IgG3 has a higher fractional catabolic rate of approximately 16.8% of the intravascular pool per day 1
• In patients with primary immunodeficiency receiving intravenous immunoglobulin (IGIV), the half-life of total IgG has been measured at 25.8 days 2

Distribution of IgG in the Body

• The intravascular compartment contains 51-54% of the total body pools of IgG1, IgG2, and IgG4 1
• For IgG3, the intravascular compartment contains a higher percentage (64%) of the total body pool 1
• This distribution pattern contributes to the overall metabolism and clearance of the different IgG subclasses 1

Clinical Implications

• In patients receiving immunoglobulin replacement therapy, the half-life of IgG affects dosing intervals 2
• Protection from passive immunization with immunoglobulin preparations typically lasts for at least one half-life of IgG (approximately 3 weeks) 3
• For example, after administration of Varicella-Zoster Immune Globulin (VZIG), protection lasts for approximately 3 weeks due to the half-life of IgG 3
• Patients with primary immunodeficiency who receive monthly IGIV infusions show similar half-lives for total IgG and specific antibodies 2

Variability in IgG Half-Life

• Half-lives of IgG can be highly variable among individuals, ranging from 22 to 96 days in some studies of patients with primary immunodeficiency 4
• The complementarity-determining regions of the heavy chain can significantly influence the IgG's binding properties to the neonatal Fc receptor (FcRn), which in turn affects half-life 5
• Glycosylation patterns of the constant region do not appear to significantly alter IgG-FcRn binding 5

Measurement and Prediction Methods

• High-throughput biolayer interferometry can be used to predict IgG half-life by measuring FcRn binding properties 5
• The combination of FcRn association rate at acidic pH and dissociation rate at physiological pH correlates strongly with clinical half-life of human IgG1 monoclonal antibodies 5