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immunological properties and clinical applications
Human immunoglobulin, also known as intravenous immunoglobulin (IVIg), is a blood product derived from pooled human plasma. The plasma is carefully tested and processed to ensure safety and standardization. IVIg contains concentrated immunoglobulin G (IgG) antibodies which can help restore immune function in certain conditions.
Composition and mechanism of action
IVIg is composed primarily of IgG antibodies that are purified from donor plasma collected from thousands of healthy individuals. Each dose therefore contains a wide variety of antibodies directed against various antigens. When administered intravenously, these preformed antibodies are able to enter the bloodstream and exert various immunomodulatory effects.
Some key mechanisms through which IVIg works include neutralizing pathogenic autoantibodies, suppressing autoantibody production, regulating immune cell function and inhibiting inflammation. Specifically, IVIg antibodies engage Fc receptor pathways on B cells, macrophages, dendritic cells and other immune cells. This modulates the immune response in a way that dampens excessive inflammation and autoimmunity. IVIg also contains anti-idiotypic antibodies that bind pathogenic autoantibodies, rendering them inactive.
Indications and clinical uses
Due to its broad range of immunomodulatory properties, IVIg therapy is approved for use in several immune-mediated conditions. Some of its major indications include:
Primary immunodeficiencies: IVIg replacement therapy provides protective antibodies for patients with primary antibody deficiencies who cannot produce sufficient antibodies on their own. It helps prevent recurrent infections in these patients.
Idiopathic thrombocytopenic purpura (ITP): IVIg works by reducing autoantibody levels against platelets, thereby raising platelet counts in ITP. This enables safe management of acute episodes and preparation for surgery in chronic ITP.
Kawasaki disease: When given together with aspirin, IVIg has been shown to reduce cardiovascular complications in Kawasaki disease by inhibiting inflammation and autoimmunity.
Guillain-Barré syndrome (GBS): As GBS is an autoimmune attack on the peripheral nerves, IVIg dampens the immune system to aid recovery. It shortens the duration of symptoms and prevents life-threatening complications in both children and adults with GBS.
Multifocal motor neuropathy (MMN): IVIg stabilizes motor function and strength in MMN by neutralizing anti-GM1 ganglioside antibodies associated with this rare autoimmune nerve disorder.
Chronic inflammatory demyelinating polyneuropathy (CIDP): Similarly, IVIg provides relief from weakness and disability in CIDP by targeting antibodies and inflammation involved in damaging peripheral nerve myelin sheaths.
Other common off-label uses of IVIg based on case reports and series include autoimmune hemolytic anemia, dermatomyositis, lupus nephritis, refractory ulcerative colitis and myasthenia gravis among others.
Administration and safety considerations
IVIg therapy usually requires intravenous infusion via a peripheral or central line. Standard infusion rates range from 0.01 to 0.1 mg/kg/minute depending on the specific product and clinical indication. Close monitoring is important during infusion owing to a small risk of adverse reactions.
While generally well-tolerated, Human Immunoglobulin (pH4) for Intravenous Injection administration can potentially cause mild infusion-related side effects such as headache, nausea and low-grade fever in up to 30% of patients. Severe adverse events like anaphylaxis, thrombosis and renal failure are quite rare (<1%). Certain individuals with underlying conditions may have an increased risk for these complications.
Precautions also include avoiding IVIg use in IgA-deficient patients due to the risk of inducing IgA antibodies that cause allergic reactions with subsequent infusions. Appropriate screening and pre-medication with antihistamines, antipyretics, steroids etc. can help mitigate adverse infusion effects when necessary.
Dosage, administration and monitoring
The dosage regimen and treatment schedule of IVIg therapy differs by indication and patient factors. As a general guideline:
– Primary immune deficiencies: A maintenance dose of 300-800 mg/kg is given every 3-4 weeks.
– ITP: A dose of 1 g/kg is divided over 2-5 days for acute therapy. Long-term dosing at intervals may be 300-400 mg/kg monthly.
– GBS: A total dose of 2 g/kg is administered in divided doses over 2-5 days for new cases.
– CIDP: Doses of 0.4-2 g/kg are given monthly for maintenance treatment.
Laboratory monitoring during and after therapy involves periodic measurement of hemoglobin levels, renal function tests as well as periodic assessment of clinical signs and symptoms relevant for each individual condition. IVIg therapy should be continued as needed to maintain clinically effective antibody levels based on treatment response for specific conditions.
Special formulations and precautions
Recent advances led to the development of IVIg formulations with neutral pH of around 4.5-5. These are better tolerated owing to less aggregation of IgG antibodies. They also show enhanced stability during infusion thereby lowering infusion-related adverse effects significantly.
While generally well-tolerated in most patients, close monitoring for side effects is required during Human Immunoglobulin (pH4) for Intravenous Injection administration. Precautions must be taken for those at higher risk of complications. Judicious use as per approved clinical guidelines helps maximize benefits safely in suitable immune-mediated conditions.
