Immunoglobulin: Polyvalent Antibodies from Plasma (IVIG, SCIG)
Immunoglobulin (Ig) is a collective term for polyvalent antibody preparations obtained from the plasma of many thousands of healthy donors. They contain predominantly immunoglobulin G (IgG) with a broad antibody repertoire against various pathogens and antigens. Well-known trade names include Privigen, Octagam, Kiovig, Gamunex, Hizentra, HyQvia and numerous other intravenous (IVIG) and subcutaneous (SCIG) preparations.
Immunoglobulin therapy has a long history and various indications, which can be roughly divided into three areas: substitution therapy for primary and secondary antibody deficiency syndromes, immunomodulation in autoimmune and inflammatory diseases, and passive immunization against specific pathogens (with specific hyperimmune globulins). These high-cost preparations require careful indication setting.
Mechanism of Action
In substitution therapy, the administered IgG replaces missing or dysfunctional endogenous antibodies. Patients with primary antibody deficiency syndromes such as X-linked agammaglobulinemia (Bruton), common variable immunodeficiency (CVID), IgG subclass deficiency, or hyper-IgM syndrome require lifelong substitution to prevent severe and chronic infections. Secondary antibody deficiencies can occur in B cell lymphomas, multiple myeloma, after stem cell transplantation, and during rituximab therapy.
In immunomodulation, high-dose IVIG (1 to 2 g/kg) acts through several mechanisms: inhibition of complement activation, blockade of Fc receptors on phagocytes, modulation of cytokine profile, inhibition of pathogenic autoantibodies through idiotypic antibodies, effects on B and T cell function. These pleiotropic effects explain efficacy in many autoimmune and inflammatory diseases.
In passive immunization, specific hyperimmune globulins contain deliberately high antibody titers against certain pathogens (hepatitis B, tetanus, rabies, varicella zoster, Rh D antigen, cytomegalovirus). These are used for post-exposure prophylaxis or therapeutically.
Applications
- Primary antibody deficiency syndromes: X-linked agammaglobulinemia, CVID, hyper-IgM syndrome, IgG subclass deficiency with clinically relevant infections
- Secondary antibody deficiency syndromes: after B cell therapies (rituximab, CAR T), in chronic lymphocytic leukemia, multiple myeloma, after stem cell transplantation
- Idiopathic thrombocytopenia (ITP): in acute life-threatening bleeding or before operations, rapid platelet increase
- Kawasaki disease in children: standard for reducing the risk of coronary aneurysms
- Guillain-Barré syndrome: first-line together with plasmapheresis
- Chronic inflammatory demyelinating polyneuropathy (CIDP): maintenance therapy
- Myasthenia gravis: in myasthenic crisis or before thymectomy
- Multifocal motor neuropathy
- Dermatomyositis and polymyositis: in refractory disease
- Post-exposure prophylaxis (hyperimmune globulins): hepatitis B, tetanus, rabies, varicella zoster
Dosage and Administration
Substitution for antibody deficiency intravenously (IVIG): 0.4 to 0.6 g/kg every 3 to 4 weeks, adjusted according to trough level and clinical course (target IgG trough level above 6 to 8 g/L or higher).
Substitution subcutaneously (SCIG, Hizentra, Cuvitru): 100 to 200 mg/kg per week, home administration possible, more consistent levels.
Immunomodulation in ITP, Kawasaki, Guillain-Barré: 2 g/kg total, distributed over 2 to 5 days.
Maintenance therapy CIDP: 1 g/kg every 3 to 4 weeks or home administration subcutaneously.
Intravenous administration: slow infusion with increasing speed, especially at the beginning, to prevent reactions. Premedication with antihistamine and possibly glucocorticoid in patients prone to reactions.
Side Effects
Common: headache, fever, chills, fatigue, nausea, hypertension, tachycardia during or after infusion. With subcutaneous administration, local reactions at injection site (swelling, redness).
Serious: anaphylactic reactions, especially in IgA deficiency with anti-IgA antibodies; thromboembolic events (stroke, pulmonary embolism, deep vein thrombosis), particularly with risk factors such as obesity, immobility, high doses, rapid infusion; acute renal failure especially with sucrose-containing preparations (rarely used today); aseptic meningitis (often at high immunomodulation doses); hemolytic anemia from anti-A or anti-B antibodies in patients with blood groups A, B or AB; transmission risk of pathogens (today minimized by virus inactivation and donor testing, but theoretically possible for emerging pathogens).
Important: transmission of pathogens such as HIV, hepatitis B/C is extremely unlikely with modern manufacturing processes using virus inactivation steps. Nevertheless, residual risk is not zero and is mentioned in patient information.
Drug Interactions
- Live vaccines (MMR, varicella, yellow fever): efficacy reduced for 3 to 11 months after IVIG, therefore vaccination beforehand or with sufficient interval
- Anticoagulants: additive thrombosis risk with IVIG, caution advised
- Diuretics and nephrotoxic drugs: additive risk for renal function deterioration
- Other intravenous therapies: do not administer through same infusion line
Special Information
Pregnancy and breastfeeding: Immunoglobulin is considered safe and is used both in pregnancy (e.g., in antibody deficiency, ITP) and during breastfeeding. Maternal IgG antibodies even protect the newborn through passive immunity.
IgA deficiency: Patients with selective IgA deficiency can develop anti-IgA antibodies, which can lead to severe anaphylactic reactions with IVIG containing IgA. IgA-poor or IgA-free preparations are available and should be used in these patients.
Before administration: History of prior reactions, IgA status, cardiovascular risk factors, renal function. In case of thromboembolic risk, adequate hydration and slow infusion.
Subcutaneous administration (SCIG): allows home administration with pump, more consistent levels and fewer systemic reactions. Patients are trained in self-administration.
Premedication: in patients prone to reactions, paracetamol, antihistamine and possibly glucocorticoid 30 minutes before IVIG can reduce reactions.
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- Azathioprine, classical immunosuppressive
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Frequently Asked Questions
What is the difference between IVIG and SCIG?
IVIG (intravenous) is administered every 3 to 4 weeks in a clinic or day clinic with infusion lasting 30 minutes to several hours. SCIG (subcutaneous) is injected weekly in smaller doses under the skin, often in home administration with a pump. SCIG offers more consistent levels, fewer systemic reactions and better quality of life, but with more frequent administrations. The choice depends on indication, patient preference and logistical factors.
Why does immunoglobulin work in both antibody deficiency and autoimmune diseases?
In antibody deficiency, IVIG replaces missing antibodies and protects against infections (substitution dose 0.4 to 0.6 g/kg). In autoimmune diseases, IVIG acts at much higher doses (2 g/kg) immunomodulatingly through complement inhibition, Fc receptor blockade and modulation of immune response. The exact mechanisms are complex and not fully understood.
Can pathogens be transmitted through immunoglobulin?
Modern manufacturing procedures with donor testing, plasma pooling, fractionation and multiple virus inactivation steps have practically eliminated the residual risk of transmission of HIV, hepatitis B and C. Theoretical risks for emerging, not yet testable pathogens exist but are very low. Patients should be informed about this in patient information.
How is therapy success monitored?
In substitution therapy, the IgG trough level is measured before each infusion, with target above 6 to 8 g/L. Clinically, the frequency and severity of infections are assessed. In immunomodulation, assessment is based on clinical disease measures (e.g., platelet count in ITP, symptom scores in CIDP, muscle strength in myasthenia gravis).
Sources
- EMA Product Information Immunoglobulin Preparations
- AWMF Guidelines Immunoglobulin Therapy and Primary Immunodeficiency
- DGHO Onkopedia, Immunoglobulin Substitution
- BfArM, Federal Institute for Drugs and Medical Devices
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