Immunoglobulin G
Also known as: IgG, gamma globulin, Immunoglobulin G
Overview
Immunoglobulin G (IgG) is the most abundant antibody isotype in human serum, produced by plasma cells as part of the adaptive immune response. It is naturally found in blood plasma and extracellular fluid. As a therapeutic agent, IgG is primarily used in immunoglobulin replacement therapy (IRT) for patients with antibody deficiencies, autoimmune diseases, and some infections. It provides long-term immunity by neutralizing pathogens, opsonization, and activating complement pathways. IgG is administered intravenously (IVIG) or subcutaneously (SCIG). While its use in replacement therapy is well-established, its application in other conditions like chronic obstructive pulmonary disease (COPD) and sepsis is under active investigation. Several systematic reviews and meta-analyses provide high-quality evidence on IgG’s clinical efficacy in specific populations, particularly those with primary immunodeficiency.
Benefits
In patients with primary immunodeficiency (PID), maintaining IgG trough levels up to approximately 960 mg/dL correlates with reduced infection rates and improved clinical outcomes. Meta-regression analyses show a dose-response relationship between IgG trough levels and infection reduction in PID, indicating clinically meaningful effects. In COPD patients with low serum IgG, IgG replacement therapy has been associated with decreased hospitalizations and emergency visits, although evidence is still emerging. IgM-enriched immunoglobulin adjunctive therapy may reduce mortality risk in neonatal and pediatric sepsis, suggesting potential benefits of immunoglobulin therapies in critical infections. The most robust benefits are seen in patients with antibody production deficiencies (e.g., PID) and possibly in COPD patients with hypogammaglobulinemia.
How it works
IgG antibodies bind to specific antigens on pathogens, neutralizing them, facilitating phagocytosis via Fc receptors, and activating the complement cascade. This interaction enhances pathogen clearance and modulates immune responses. IgG acts within the immune system, targeting Fc gamma receptors on immune cells and complement proteins. Therapeutic IgG is administered intravenously (IVIG) or subcutaneously (SCIG), with bioavailability depending on the route. SCIG provides more stable serum levels, ensuring consistent immune support.
Side effects
IgG replacement therapy is generally safe with a well-characterized safety profile. Common side effects (>5%) include mild infusion reactions such as headache, chills, fever, and fatigue. Uncommon side effects (1-5%) include allergic reactions, thromboembolic events, and hemolysis. Rare side effects (<1%) include aseptic meningitis and renal dysfunction. There are no major drug interactions reported, but caution is advised with live vaccines. Contraindications include known hypersensitivity to immunoglobulin preparations. Dose adjustments and monitoring are required in patients with renal impairment and cardiovascular risk factors. Patients should be monitored for hypersensitivity reactions and thromboembolic events, especially those with pre-existing risk factors.
Dosage
In PID, doses typically start at 400–600 mg/kg/month to maintain protective IgG trough levels. Dosage is adjusted to maintain trough levels around 700–1000 mg/dL depending on clinical response. The maximum safe dose is generally up to 2 g/kg/month; higher doses increase the risk of adverse effects. Regular dosing intervals (monthly for IVIG, weekly or biweekly for SCIG) are necessary to maintain stable IgG levels. IVIG is used for rapid replacement, while SCIG is used for steady-state maintenance. SCIG absorption is slower but more consistent, while IVIG achieves higher peak levels. Hydration is recommended to reduce adverse events.
FAQs
Is IgG supplementation safe for long-term use?
Yes, long-term IgG replacement therapy is safe and effective in PID patients when administered and monitored by healthcare professionals.
How quickly can benefits be expected?
Infection reduction benefits typically appear within months of achieving adequate IgG trough levels through consistent replacement therapy.
Can IgG be used for conditions other than immunodeficiency?
Emerging evidence supports use in COPD with low IgG and in sepsis adjunctive therapy, but these are not yet standard indications and require further research.
Are there differences between IVIG and SCIG?
Yes, IVIG offers a rapid serum level increase, while SCIG provides more stable levels with fewer systemic side effects, making it suitable for steady-state maintenance.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/34070826/ – This systematic review and meta-analysis confirmed the therapeutic use of IgG in antibody deficiencies. The study highlighted variability in IgG levels and outcomes, emphasizing the need for personalized treatment approaches. It provides a high-quality synthesis of existing research on IgG therapy.
- https://pmc.ncbi.nlm.nih.gov/articles/PMC11005196/ – This systematic review focused on COPD patients with low IgG levels and found that IgG replacement may reduce hospitalizations and exacerbations in this population. The evidence is still emerging, with limited RCT data and small sample sizes, indicating a need for further research to confirm these benefits.
- https://publications.aap.org/pediatrics/article/148/Supplement%203/S67/183591/A-Systematic-Review-and-Meta-Regression-Analysis – This systematic review and meta-regression analysis in PID patients treated with IVIG (n≥30) found that increasing IgG trough levels up to approximately 960 mg/dL was associated with reduced infections and improved outcomes. The study provides high-quality evidence supporting a dose-response relationship between IgG levels and clinical benefits in PID.
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.664526/full – This study investigated the influence of age and sex on IgG levels, which may affect baseline immunity and response to therapy. The research highlights the importance of considering these factors when assessing immune function and tailoring treatment strategies.
- https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1239014/full – This meta-analysis on neonatal and pediatric sepsis patients found that IgM-enriched immunoglobulin adjunctive therapy reduced mortality risk. While the focus is on IgM-enriched immunoglobulin, the findings suggest potential benefits of immunoglobulin therapies in critical infections, although heterogeneity in studies should be considered.
