Immunoglobulin therapy is the use of a mixture of antibodies (normal human immunoglobulin) to treat several health conditions.
Common side effects include pain at the site of injection, muscle pain, and allergic reactions. Other severe side effects include kidney problems, anaphylaxis, blood clots, and red blood cell breakdown. Use is not recommended in people with some types of IgA deficiency. Use appears to be relatively safe during pregnancy. Human immunoglobulin is made from human blood plasma. It contains antibodies against many viruses.
Human immunoglobulin therapy first occurred in the 1930s and a formulation for injection into a vein was approved for medical use in the United States in 1981.
It is on the World Health Organization's List of Essential Medicines. Each formulation of the product is somewhat different. A number of specific immunoglobulin formulations are also available including for hepatitis B, rabies, tetanus, varicella infection, and Rh positive blood exposure.
Immunoglobulin therapy is especially useful in some acute infection cases such as pediatry HIV infection and is also considered the standard of treatment for some autoimmune disorders such as Guillain–Barré syndrome. The high demand which coupled with the difficulty of producing immunoglobulin in large quantities has resulted in increasing global shortages, usage limitations and rationing of immunoglobulin.
Subcutaneous immunoglobulin access programs have been developed to facilitate hospital based programs.
Human normal immunoglobulin (human immunoglobulin G) (Cutaquig) was approved for medical use in Australia in May 2021.
In the European Union, human normal immunoglobulin (SCIg) (Hizentra) is used in people whose blood does not contain enough antibodies (proteins that help the body to fight infections and other diseases), also known as immunoglobulins. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. It is used to treat the following conditions:
It is indicated for replacement therapy in adults and children in primary immunodeficiency syndromes such as:
Flebogamma DIF is indicated for the replacement therapy in adults, children and adolescents (0–18 years) in:
and for the immunomodulation in adults, children and adolescents (0–18 years) in:
In February 2025, the Committee for Medicinal Products for Human Use of the European Medicines Agency adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product ., intended for replacement therapy in people with primary or secondary immunodeficiencies and immunomodulation in people with certain autoimmune diseases. The applicant for this medicinal product is Takeda Manufacturing Austria AG. Deqsiga is a duplicate of Kiovig (human normal immunoglobulin), which was authorized in the EU in January 2006. Deqsiga and Kiovig have the same pharmaceutical form, active substance and indications, but Deqsiga contains lower levels of immunoglobulin A (IgA) and may therefore be more suitable for people with IgA deficiency who have a higher risk of hypersensitivity to immunoglobulin products that contain higher levels of IgA. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Deqsiga was authorized for medical use in the European Union in May 2025.
Brands include:
Local side effects of immunoglobulin infusions most frequently include an injection site reaction (reddening of the skin around the injection site), itching, rash, and hives. Less serious systemic side effects to immunoglobulin infusions include an increased heart rate, hyper or hypotension, an increased body temperature, diarrhea, nausea, abdominal pain, vomiting, arthralgia or myalgia, dizziness, headache, fatigue, fever, and pain.
Serious side effects of immunoglobulin infusions in infants, children, and adults include chest discomfort or pain, myocardial infarction, tachycardia, hyponatremia, hemolysis, hemolytic anemia, thrombosis, hepatitis, anaphylaxis, backache, aseptic meningitis, acute kidney injury, hypokalemic nephropathy, pulmonary embolism, and transfusion related acute lung injury. There is also a small chance that even given the precautions taken in preparing immunoglobulin preparations, an immunoglobulin infusion may pass a virus to its recipient. Some immunoglobulin solutions also contain isohemagglutinins, which in rare circumstances can cause hemolysis by the isohemagglutinins triggering phagocytosis.
IVIG has long been known to induce a decrease in peripheral blood neutrophil count, or neutropenia in neonates, and in patients with Idiopathic Thrombocytopenic Purpura, resolving spontaneously and without complications within 48 h. Possible pathomechanisms include apoptosis/cell death due to antineutrophil antibodies with or without neutrophil migration into a storage pool outside the blood circulation.
Immunoglobulin therapy interferes with the ability of the body to produce a normal immune response to an attenuated live-virus vaccine (like MMR) for up to a year, can result in falsely elevated blood glucose levels, and can interfere with many of the IgG-based assays often used to diagnose a patient with a particular infection.
During the late 1980s and early 1990s, it became obvious that for at least a subset of patients the systemic adverse events associated with intravenous therapy were still not easily tolerable, and more doctors began to experiment with subcutaneous immunoglobulin administration, culminating in an ad hoc clinical trial in Sweden of 3000 subcutaneous injections administered to 25 adults (most of whom had previously experienced systemic adverse effects with IMIg or IVIg), where no infusion in the ad hoc trial resulted in a severe systemic adverse reaction, and most subcutaneous injections were able to be administered in non-hospital settings, allowing for considerably more freedom for the people involved.
In the later 1990s, large-scale trials began in Europe to test the feasibility of subcutaneous immunoglobulin administration, although it was not until 2006 that the first subcutaneous-specific preparation of immunoglobulin was approved by a major regulatory agency (Vivaglobin, which was voluntarily discontinued in 2011). A number of other brand names of subcutaneous immunoglobulin have since been approved, although some small-scale studies have indicated that a particular cohort of patients with common variable immunodeficiency (CVID) may develop intolerable side effects with subcutaneous immunoglobulin (SCIg) that they do not with intravenous immunoglobulin (IVIg).
Although intravenous was the preferred route for immunoglobulin therapy for many years, in 2006, the US Food and Drug Administration (FDA) approved the first preparation of immunoglobulin that was designed exclusively for subcutaneous use.
Perhaps a more popular theory is that the immunosuppressive effects of immunoglobulin therapy are mediated through IgG's Fc glycosylation. By binding to receptors on antigen presenting cells, IVIG can increase the expression of the inhibitory Fc receptor, FcgRIIB, and shorten the half-life of auto-reactive antibodies. The ability of immunoglobulin therapy to suppress pathogenic immune responses by this mechanism is dependent on the presence of a sialylated glycan at position CH2-84.4 of IgG. Specifically, de-sialylated preparations of immunoglobulin lose their therapeutic activity and the anti-inflammatory effects of IVIG can be recapitulated by administration of recombinant sialylated IgG1 Fc.
Sialylated-Fc-dependent mechanism was not reproduced in other experimental models suggesting that this mechanism is functional under a particular disease or experimental settings. On the other hand, several other mechanisms of action and the actual primary targets of immunoglobulin therapy have been reported. In particular, F(ab')2-dependent action of immunoglobulin to inhibit activation of human dendritic cells, induction of autophagy, induction of COX-2-dependent PGE-2 in human dendritic cells leading to expansion of regulatory T cells, inhibition of pathogenic Th17 responses, and induction of human basophil activation and IL-4 induction via anti-IgE autoantibodies. Some believe that immunoglobulin therapy may work via a multi-step model where the injected immunoglobulin first forms a type of immune complex in the patient. Once these immune complexes are formed, they can interact with Fc receptors on dendritic cells, which then mediate anti-inflammatory effects helping to reduce the severity of the autoimmune disease or inflammatory state.
Other proposed mechanisms include the possibility that donor antibodies may bind directly with the abnormal host antibodies, stimulating their removal; the possibility that IgG stimulates the host's complement system, leading to enhanced removal of all antibodies, including the harmful ones; and the ability of immunoglobulin to block the antibody receptors on immune cells (), leading to decreased damage by these cells, or regulation of macrophage phagocytosis. Indeed, it is becoming more clear that immunoglobulin can bind to a number of membrane receptors on T cells, B cells, and monocytes that are pertinent to autoreactivity and induction of tolerance to self.
A report stated that immunoglobulin application to activated T cells leads to their decreased ability to engage microglia. As a result of immunoglobulin 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 immunoglobulin may affect inflammation of the central nervous system in autoimmune inflammatory diseases.
Hyperimmune serum and Blood plasma contain high amounts of an antibody, as a consequence of disease convalescence or of repeated immunization. Hyperimmune plasma is used in veterinary medicine, and hyperimmune plasma derivatives are used to treat snakebite. It has been hypothesized that hyperimmune serum may be an effective therapy for persons infected with the Ebola virus.
In Australia, blood donation is voluntary and therefore to cope with increasing demand and to reduce the shortages of locally produced immunoglobulin, several programs have been undertaken including adopting plasma for first time blood donors, better processes for donation, plasma donor centres and encouraging current blood donors to consider plasma only donation.
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