Intravenous immunoglobulin (IVIG) is a blood product administered intravenously. It contains the pooled, polyvalent, IgGantibodies 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 four major disease categories:
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.
Asthma is a condition which can have many causes. In people with both immune abnormalities and an infection causing asthma, the triggering infection could be eliminated with IVIG therapy. However, most people with asthma 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. IVIG is not recommended for recurrent asthma infections unless the person presents an impaired response to vaccine immunizations or natural infections.
Although routine use of IVIG is common practice, sometimes for long term treatments, and is considered safe, complications of IVIG therapy are known and include:
dermatitis - usually peeling of the skin of the palms and soles.
infection (such as HIV or viral hepatitis) by contaminated blood product; there is also an as yet unknown risk of contracting variant CJD (vCJD) however the process whereby the product is extracted shows that the contaminants are usually not present in the product.
allergic/anaphylactic reactions; for example, anaphylactic shock, especially in IgA deficient patients, who by definition can still produce IgG antibodies (IgA deficient patients are more likely to produce IgG against the IVIG administration than normal patients).
damage such as hepatitis caused directly by antibodies contained in the pooled IVIG.
The precise mechanism by which IVIG suppresses harmful inflammation has not been definitively established but is believed to involve the inhibitory Fc receptor. 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. Once these immune complexes are formed, they interact with activating Fc receptors on dendritic cells 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 of antibody 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. Recent studies on T cell regulatory epitopes, Tregtiopes, might explain some of the tolerogenic and regulatory effects of IVIG.
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.
IVIG is an infusion of IgGantibodies only. Therefore, peripheral tissues that are defended mainly by IgA antibodies, such as the eyes, lungs, gut and urinary tract are not fully protected by the IVIG treatment.
X-linked agammaglobulinemia patients are immune to the most dangerous adverse effect, anaphylactic shock, as they do not have the antibodies to react against the treatment. Anaphylactic shock has a higher chance to occur in IgA deficient patients which do have other antibody types.
In case of recurring side effects, it is recommended to slow the pace of the IVIG administration and to reduce the dosage. It is also advisable to change IVIG brand, as some people react against a specific brand.
If the patients are diabetic, they should take into consideration the medium in which the antibodies are solubilized in the IVIG treatment, as some brand solubilize antibodies with high concentrated sugars (such as sucrose and maltose).
IVIG is also used as a treatment for unexplained recurring miscarriages. The effectiveness of the therapy is controversial.
IVIG cost is stable but over $75/g. ($15,000 for a 100 kg (220 lbs) person at 2g/kg)
National Advisory Committee on Blood and Blood Products of Canada (NAC) and Canadian Blood Services has developed an evidence-based practice guideline on the use of IVIG for hematologic conditions. IVIG is
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
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 .
^ abcPrimary Immunodeficiency Committee Of The American Academy Of Allergy; Orange, J.; Hossny, E.; Weiler, C.; Ballow, M.; Berger, M.; Bonilla, F.; Buckley, R.; Chinen, J.; El-Gamal, Y.; Mazer, B.; Nelson Jr, R. P.; Patel, D. D.; Secord, E.; Sorensen, R. U.; Wasserman, R. L.; Cunningham-Rundles, C. (2006). "Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology". Journal of Allergy and Clinical Immunology117 (4): S525–S553. doi:10.1016/j.jaci.2006.01.015. PMID16580469.edit
^Siragam V, Crow AR, Brinc D, Song S, Freedman J, Lazarus AH (June 2006). "Intravenous immunoglobulin ameliorates ITP via activating Fc gamma receptors on dendritic cells". Nat. Med.12 (6): 688–92. doi:10.1038/nm1416. PMID16715090.
^Bayry J, Thirion M, Misra N, et al. (October 2003). "Mechanisms of action of intravenous immunoglobulin in autoimmune and inflammatory diseases". Neurol. Sci. 24 Suppl 4: S217–21. doi:10.1007/s10072-003-0081-7. PMID14598046.
^Shutty, B; Garg, KJ; Swender, D; Chernin, L; Tcheurekdjian, H; Hostoffer, R (July 2012). "Optimal use of ivig in a patient with Behçet syndrome and common variable immunodeficiency". Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology109 (1): 84. doi:10.1016/j.anai.2012.05.014. PMID22727170.
^Laupland KB, Kirkpatrick AW, Delaney A (December 2007). "Polyclonal intravenous immunoglobulin for the treatment of severe sepsis and septic shock in critically ill adults: a systematic review and meta-analysis". Crit. Care Med.35 (12): 2686–92. doi:10.1097/01.CCM.0000295312.13466.1C. PMID18074465.