Introduction

Human immunoglobulin G (IgG) contains antibodies that help fight infection. It plays an important role in immune system function. IgG is present in plasma collected from large pools of healthy human blood donors. When purified and concentrated, it can be administered intravenously to patients with certain disorders affecting the immune system.

Composition and Manufacturing
Human immunoglobulin (pH4) for intravenous injection contains purified antibodies extracted from pooled blood plasma of at least 1000 donors. The manufacturing process uses a series of fractionation, purification and virus inactivation/removal steps. The final product is sterile, pyrogen-free IgG solution at a concentration of 5-10% with a pH of 4-4.5. This low pH enhances stability and helps inactivate viruses. Efficacy and safety profiles have been established through clinical trials and post-marketing experience.

Uses and Mechanism of Action
Human immunoglobulin preparations may be used to treat several conditions involving immune deficiencies. The mechanism involves passive immunization against infectious agents by supplementing antibodies that the patient is unable to produce on their own.

Primary Immunodeficiencies
Patients with primary antibody deficiencies such as common variable immunodeficiency, X-linked agammaglobulinemia or severe combined immunodeficiency are prone to recurrent, persistent, and potentially life-threatening infections. Regular intravenous immunoglobulin administration helps protect against infections by restoring antibody levels.

Kawasaki Disease
Patients with acute Kawasaki disease are at high risk of developing coronary artery abnormalities including aneurysms. Early initiation of immunoglobulin along with aspirin reduces the risk of coronary complications likely by modulating the inflammatory response.

Guillain-Barré Syndrome
Immunoglobulin administered for 5 days provides short term benefits in reducing mortality and duration of ventilation in patients with severe Guillain-Barré syndrome compared to supportive care alone. The mechanism is thought to involve inhibition of complement and Fc receptor binding, leading to reduced nerve demyelination.

Prevention of Infection in Immune-compromised Patients
Human immunoglobulin is used pre- and post-transplant to provide passive immunity and prevent recurrent bacterial infections in patients undergoing bone marrow or solid organ transplantation. It also finds use as prophylaxis against infection in patients receiving chemotherapy or immunosuppressants.

Efficacy and Clinical Data
Large, randomized controlled trials and meta-analyses have established efficacy in preventing infections in patients with primary immunodeficiencies.

A meta-analysis of 11 randomized controlled trials involving 238 children with Kawasaki disease showed that intravenous immunoglobulin plus aspirin reduces the incidence of coronary artery abnormalities compared to aspirin alone.

In Guillain-Barré syndrome, two large trials demonstrated that immunoglobulin treatment leads to more rapid improvement in disability scores and shorter hospital stays than supportive care. Mortality was also lower with immunoglobulin.

Safety
When used as directed, human immunoglobulin intravenous therapy is generally well tolerated. Most common adverse reactions seen are headache, fever, chills, vomiting, allergic reactions etc. which are usually mild and self-limiting. On rare occasions, severe anaphylactic reactions may occur. Careful selection of patients, slow infusion rates and premedication helps minimize risks. Thrombotic events have rarely been reported particularly in patients with risk factors. Strict aseptic preparation and administration techniques are followed to prevent transmission of infectious agents. Overall, the benefits outweigh risks when used to treat approved conditions.

Precautions and Consents
As immunoglobulin is derived from human blood, precautions are taken to screen donors and employ manufacturing steps to eliminate potential infectious agents including viruses. While the risk is extremely low, patients should be educated about slight theoretical risk of transmission of rare infectious diseases. Written informed consents are required from patients or their legal guardians before treatment initiation. Vital signs and reactions are closely monitored during and after infusions.

Storage and Handling
The solution is stable for 3 years if stored between 2-8°C and should not be frozen. It needs to be brought to room temperature slowly and gently inverted prior to use. Administration sets with in-line filters help remove particulates and prevent risks of thrombosis. Expired, contaminated or turbid preparations must be discarded safely according to biowaste protocols.

Conclusion
Intravenous immunoglobulin plays a major role in management of immune deficiencies and selected inflammatory conditions by restoring humoral immunity. Clinical experience plus rigorous manufacturing standards have established it as a safe and effective replacement treatment option offering protection from infections. When administered properly and monitored carefully by health professionals, it improves quality of life for many patients. Further research continues to explore new applications.