Immunoglobulins G
Also known as: IgG, gamma globulin, Immunoglobulin G
Overview
Immunoglobulin G (IgG) is the most abundant antibody isotype in human serum, playing a crucial role in the adaptive immune response. Produced by plasma cells, IgG is found in blood plasma and extracellular fluid. It comprises four subclasses (IgG1, IgG2, IgG3, IgG4), each with distinct immune functions, including neutralizing pathogens, opsonizing for phagocytosis, and activating the complement system. Therapeutically, IgG is administered intravenously (IVIG) or subcutaneously to treat immunodeficiencies, autoimmune diseases, and certain infections. Research also explores its adjunctive use in conditions like autism spectrum disorder (ASD) and sepsis. Extensive research supports IgG's immunological roles and therapeutic applications, with numerous randomized controlled trials and systematic reviews. While high-quality evidence supports its use in immunodeficiency and autoimmune conditions, evidence for other indications is still emerging and less definitive. Oral IgG has limited systemic absorption but may act locally in the gut.
Benefits
IgG is highly effective in treating immunodeficiency by reducing infection rates in patients with primary immunodeficiencies. In autoimmune and inflammatory diseases, IVIG modulates the immune response, reducing disease activity in conditions like immune thrombocytopenia and Kawasaki disease. Meta-analyses suggest that IgM-enriched immunoglobulin formulations may reduce mortality in neonatal and pediatric sepsis, although evidence varies by study design and population. Some systematic reviews indicate altered IgG profiles in ASD and possible benefits from IVIG, but this evidence remains preliminary and inconclusive. Neonates and immunocompromised patients benefit most clearly from IgG supplementation. Meta-analyses show statistically significant mortality reduction in sepsis with IgM-enriched immunoglobulin adjunct therapy.
How it works
IgG neutralizes pathogens by binding to antigens, preventing them from infecting cells. It facilitates opsonization, where IgG coats pathogens, making them more easily recognized and engulfed by phagocytes. IgG also activates the complement cascade, a series of proteins that lead to pathogen lysis. These actions modulate the immune system by balancing pro- and anti-inflammatory signals. IgG interacts with Fc gamma receptors on immune cells and complement proteins. IVIG is administered intravenously for systemic availability, while oral IgG has limited systemic absorption but may act locally in the gut.
Side effects
IVIG is generally safe but can cause side effects. Common side effects (>5%) include mild infusion reactions such as headache, fever, chills, and fatigue. Uncommon side effects (1-5%) include thromboembolic events, renal dysfunction, and hemolysis. Rare side effects (<1%) include anaphylaxis and aseptic meningitis. Caution is advised when administering live vaccines concurrently, as IgG may interfere with their efficacy. It may also interact with immunosuppressants. IgA deficiency with anti-IgA antibodies is a contraindication due to the risk of severe reactions. Neonates and elderly patients require careful dosing and monitoring. Hydration is recommended to reduce the risk of renal complications.
Dosage
For immunodeficiency, typical IVIG doses range from 400-600 mg/kg every 3-4 weeks. For sepsis adjunct therapy, IgM-enriched immunoglobulin doses of 250 mg/kg/day for 3 days are commonly used. The maximum safe dose is generally up to 2 g/kg per infusion cycle, depending on individual tolerance. Dosing intervals depend on the specific condition; acute conditions require prompt administration. IVIG is the standard form, as oral IgG supplementation lacks systemic efficacy evidence. IV administration bypasses absorption barriers. Hydration is recommended to reduce renal risk. Dosing should be carefully monitored, especially in neonates and elderly patients.
FAQs
Is IgG supplementation safe?
Yes, IVIG is generally safe with known and manageable side effects. However, it's crucial to monitor for potential adverse reactions, especially in vulnerable populations.
Can oral IgG supplements replace IVIG?
No, oral IgG has limited systemic absorption and is not a substitute for IVIG, which is administered intravenously for systemic availability.
How soon do benefits appear?
The time frame for observing benefits depends on the condition being treated. Acute benefits may appear within days, while chronic conditions may require longer treatment periods.
Does IgG cure diseases?
IgG modulates immune function but does not cure underlying diseases. It helps manage symptoms and reduce the severity of certain conditions.
Are there risks of allergic reactions?
Allergic reactions are rare but possible, especially in IgA-deficient individuals. Healthcare providers should be prepared to manage anaphylaxis if it occurs.
Research Sources
- https://pubmed.ncbi.nlm.nih.gov/34070826/ – This systematic review and meta-analysis examined multiple studies on ASD patients and found IgG abnormalities in ASD. It suggests that IVIG may have therapeutic potential, but the evidence is preliminary due to heterogeneity and small sample sizes in some studies, highlighting the need for RCTs.
- https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.664526/full – This systematic review analyzed 117 studies on serum Ig levels in adults, identifying determinants such as age, sex, and health status. The study provides a comprehensive overview of factors influencing IgG levels, although it is based on observational data and exhibits some heterogeneity.
- https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2023.1239014/full – This meta-analysis of RCTs and observational studies focused on neonatal and pediatric sepsis patients, finding that IgM-enriched immunoglobulin adjunct therapy reduces mortality in sepsis. The study's robust statistical methods support its findings, although some heterogeneity and variable study quality were noted.
- https://www.mdpi.com/2072-6643/12/4/1023 – This study investigates the effects of bovine colostrum supplementation, a source of IgG, on gut health and immune function. It highlights the potential benefits of IgG in modulating the gut microbiome and reducing inflammation, particularly in individuals with compromised gut barrier function.
- https://onlinelibrary.wiley.com/doi/abs/10.1111/ctr.13625 – This review examines the use of intravenous immunoglobulin (IVIg) in the treatment of chronic inflammatory demyelinating polyneuropathy (CIDP). It discusses the mechanisms of action of IVIg in CIDP and provides an overview of clinical trials evaluating its efficacy and safety.