IVIG
Also Known As: IVIG, Intravenous immunoglobulin
Intravenous immunoglobulin (IVIG) is a blood product administered intravenously. It contains the pooled, polyvalent, IgG (immunoglobulin(antibody) G) extracted from the plasma of over one thousand blood donors. IVIG's effects last between 2 weeks and 3 months. It is mainly used as treatment in three major categories:
- Immune deficiencies such as X-linked agammaglobulinemia (XLA), hypogammaglobulinemia (primary immune deficiencies), and acquired compromised immunity conditions (secondary immune deficiencies) featuring low antibody levels.
- Autoimmune diseases, e.g. immune thrombocytopenia (ITP), and inflammatory diseases, e.g. Kawasaki disease.
- Acute infections.
Researchers are currently investigating the use of IVIG in early Alzheimer's disease, with encouraging results.
IVIG use
IVIG is given as a plasma protein replacement therapy (IgG) for immune deficient patients who have decreased or abolished antibody production capabilities. In these immune deficient patients, IVIG is administered to maintain adequate antibody levels to prevent infections and confers a passive immunity. Treatment is given every 3–4 weeks. In the case of patients with autoimmune disease, IVIG is administered at a high dose (generally 1-2 grams IVIG per kg body weight) to attempt to decrease the severity of the autoimmune diseases such as dermatomyositis. Currently, IVIg is being increasingly used off-label in a number of pathological conditions; the increasing world-wide usage of IVIg may lead to shortages of this beneficial drug.
IVIG is useful in some acute infection cases such as pediatric HIV infection as well as autoimmune, such as Guillain–Barré syndrome.[1]
As asthma treatment
Asthma is a condition which can have many causes. In patients with both immune abnormalities and an infection causing asthma, the triggering infection could be eliminated with IVIG therapy.[2] However, most asthma patients have a normal immune system and their asthma is the result of lower airway inflammation which can be managed in the context of a healthy immune system.[2][3] Despite popularity of use, IVIG is not recommended for recurrent asthma infections unless the patient presents an impaired response to vaccine immunizations or natural infections.[2][3]
Mechanism of action
The precise mechanism by which IVIG suppresses harmful inflammation has not been definitively established but is believed to involve the inhibitory Fc receptor.[4][5] However, the actual primary target(s) of IVIG in autoimmune disease are still unclear. IVIG may work via a multi-step model where the injected IVIG first forms a type of immune complex in the patient.[6] Once these immune complexes are formed, they interact with activating Fc receptors on dendritic cells[7] which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state.
Additionally, the donor antibody may bind directly with the abnormal host antibody, stimulating its removal. Alternatively, the massive quantity ofantibody may stimulate the host's complement system, leading to enhanced removal of all antibodies, including the harmful ones. IVIG also blocks the antibody receptors on immune cells (macrophages), leading to decreased damage by these cells, or regulation of macrophage phagocytosis.
IVIG may also regulate the immune response by reacting with a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.[8]
A recent report stated that IVIG application to activated T cells leads to their decreased ability to engage microglia. As a result of IVIG treatment of T cells, the findings showed reduced levels of tumor necrosis factor-alpha and interleukin-10 in T cell-microglia co-culture. The results add to the understanding of how IVIG may affect inflammation of the central nervous system in autoimmune inflammatory diseases.[9]
- Allogeneic bone marrow transplant
- Chronic lymphocytic leukemia
- Common variable immunodeficiency (CVID) a group of approximately 150 primary immunodeficiencies (PIDs), which have a common set of features (including hypogammaglobulinemia) but which have different underlying causes
- Idiopathic thrombocytopenic purpura
- Pediatric HIV
- Primary immunodeficiencies
- Kawasaki disease
- Chronic inflammatory demyelinating polyneuropathy (CIDP). Only the "Gamunex" brand manufactured by Talecris is approved for CIDP (in 2008), under the U.S. Orphan Drug law provisions
- Kidney transplant with a high antibody recipient or with an ABO incompatible donor
In 2004 the FDA approved the Cedars-Sinai IVIG Protocol which has been 90-95% successful in removing antibodies from the blood of kidney transplant recipients so that they can accept a living donor kidney from any healthy donor no matter blood type (ABO incompatible) or tissue match.
In Phase III testing in the US (as of December 2008)
Early experimental results in 2012 from a small clinical trial in humans have shown hints that it may protect against the progression of Alzheimer's Disease.[10][11]
According to experts at the Alzheimer's Association International Conference 2012 in Vancouver, the immune therapy called IVIG/Gammagard is first long-term treatment shown to halt the progression of Alzheimer's disease. [12]