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What is IVIG?

Intravenous immunoglobulin (IVIG) is a blood product that contains the pooled immunoglobulin G (IgG) prepared from the serum of at least a thousand blood donors. An immunoglobulin (Ig) is an antibody or a protein that has a large, Y-shaped molecule, mainly produced by plasma cells. It is used by the body’s immune system to identify and counteract foreign elements such as viruses and bacteria.

IVIG may be used as treatment for patients with antibody deficiencies. It is used as a ‘replacement’ at a dose of 200–400 mg/kg body weight, and is given approximately every 3 weeks. In some patients, ‘high dose’ IVIG (around 2 g/kg/month) is used as an ‘immunomodulatory’ agent to treat inflammatory and immune disorders.

Clinical specialities using IVIG include immunology, rheumatology, neurology, hematology, nephrology, and dermatology. Its use has major impact on the treatment of various disorders including Guillain–Barre syndrome, myasthenia gravis, systemic lupus erythematosis (SLE), rheumatoid arthritis, and many other diseases.

The US Food and Drug Administration (FDA) has approved the use of IVIG to treat conditions such as:

  • Bone marrow transplantation
  • Chronic B-cell lymphocytic leukemia
  • Chronic lymphocytic leukemia
  • Hematopoietic stem cell transplantation
  • Immune-mediated thrombocytopenia
  • Kawasaki disease
  • Kidney transplantation
  • Pediatric HIV type 1 infection
  • Primary immunodeficiency disorders

Off-label applications include:

  • Hematology – conditions such as aplastic anemia and thrombotic thrombocytopenia purpura
  • Infectious diseases – Prophylaxis in patients with low birth weight, surgery, trauma, burns, solid organ transplantation, and HIV infection.
  • Neurology – for epilepsy, Guillain-Barré syndrome, Myasthenia gravis
  • Obstetrics – for recurrent pregnancy loss
  • Pulmonology – for asthma
  • Rheumatology – for rheumatoid arthritis, systemic lupus erythematosus, polymyositis
  • Miscellaneous – for amyotrophic lateral sclerosis, acute cardiomyopathy, chronic fatigue syndrome, diabetes mellitus, multiple myeloma

How IVIG Works?

An antibody or immunoglobulin recognizes a harmful agent, or antigen, and binds it with precision, tagging a microbe or a cell for attack by other components of the immune system. It can also neutralize its target directly. The binding may hinder biological processes causing disease or may it recruit other cells to destroy a foreign substance.

Antibodies are produced by B cells of the immune system and they can occur in two forms – one is a soluble form that is free in the plasma, and the other is attached to the surface of B cells (B-cell receptor or BCR). The BCR facilitates activation and development of cells into either plasma cells, which produce more antibodies, or memory B cells that remember the antigens so that the B cells respond faster in future exposure to the antigen.

The mechanism of action of IVIG are complex, but the predominant mechanism depends on the immunoglobulin dose and the disease process being treated. As an immunomodulating agent, IVIG works in many ways. It can:

  • Modulate complement activation
  • Suppressidiotypic antibodies
  • Saturate Fc receptors on macrophages
  • Suppress various inflammatory mediators such as cytokines
  • Block macrophage Fc
  • Inhibit the generation of membrane attack complexes
  • Induce a decrease in plasma levels of membrane attack complex
  • Neutralize autoantibodies

IVIG has an excellent safety record and is used to avoid the side effects of steroids or other immunosuppressive agents often given to patients. Because of this, more research is being done on the possible uses of IVIG in a wide range of conditions including organ transplantation, heart failure, adult respiratory distress syndrome, encephalitis, epilepsy, fibrosis, connective tissue disease, and Alzheimer’s disease.