The majority of people diagnosed with PI have defects in their immune system’s ability to make antibodies to fight infections. These illnesses, such as common variable immune deficiency (CVID), X-linked agammaglobulinemia (XLA), and other disorders, are characterized by a lack of and/or impaired antibody function. Consequently, individuals with these PIs rely on life-long, life-saving immunoglobulin (Ig) replacement therapy. Ig comes from human plasma and is used to replace the antibodies that are needed to protect them from life-threatening infections.
Immunoglobulin, also known as gamma globulin or immune globulin, refers to the component of blood plasma that contains immunoglobulins or antibodies. These antibodies are used in the body to neutralize bacteria and viruses. They are large, Y-shaped proteins produced by specialized lymphocytes called plasma cells. The immunoglobulins in the serum or plasma are IgG, IgM, IgA, IgD, and IgE. Individuals who are unable to produce adequate amounts of antibodies may benefit from Ig replacement therapy. Only the IgG is purified from the plasma to produce therapeutic Ig products, so Ig used for treatment contains 95-98% pure IgG with small amounts of other plasma proteins including some IgA. Ig replacement therapy was first used to prevent infectious diseases in World War II and was first given as treatment for PI in 1952.
Ig is prepared from the plasma collected from a large number of individuals with a normal immune system, usually between 10,000-50,000, and who have been carefully screened to make sure that they are healthy and do not harbor certain infectious diseases. There are multiple safety steps in the production of Ig. Donor screening, viral removal, and inactivation of viruses are crucial to safe manufacturing.
All plasma donors undergo a very rigorous screening process and cannot give their plasma unless they pass this screening. Donors are asked specific questions about risk factors that could affect the safety of the donation and are deferred from donation if risk factors are identified. Plasma collection centers can look at the donation history for each donor. The U.S. Food and Drug Administration (FDA) also requires centers to maintain lists of unsuitable donors to prevent further donations from these rejected donors. As an added protection, donors must return to donate within a set timeframe for rescreening. If a donor does not return within that timeframe, their prior plasma donation will be discarded.
The first step in Ig production is to remove all the red and white blood cells. This is frequently done right as it comes out of the donor’s arm by a process called plasmapheresis, which collects plasma and then returns the red and white cells directly back to the donor.
After donation, the individually donated plasma is tested for infectious agents before being pooled with plasma from other donors. Once the plasma is pooled, the entire pool is tested for HIV and hepatitis A, B, and C viruses. The pooled plasma is then divided up and different methods of fractionation and filtration help to separate out the actual IgG molecule. At multiple times throughout this process, the pool is tested for viral safety before additional safety measures are implemented.
Ig replacement therapy only partly replaces what the body should be making, and it does not stimulate the patient’s own immune system to make more Ig. The Ig only provides temporary protection. Most antibodies, whether produced by the patient’s own immune system or given in the form of Ig replacement, are used up or “metabolized” by the body and must be constantly replenished.
Approximately half of the infused antibodies are metabolized over three to four weeks, so repeat doses of Ig are required at regular intervals. Depending on the route of administration, this may be done by giving small infusions under the skin (subcutaneous immunoglobulin or SCIG) weekly or as often as every one to three days, or by giving larger intravenous immunoglobulin (IVIG) infusions once every three or four weeks. Since Ig only replaces the missing end product but does not correct the patient’s defect in antibody production, Ig replacement is usually necessary for the patient’s lifetime.
This is why donating plasma matters.
The more plasma that is donated, the more product can be made. The process by which human plasma is collected, tested, and eventually fractionated into plasma products, like Ig, is complex. The impact is simple. Ig replacement therapy is lifesaving; it can reduce the susceptibility to infections, optimize patient health, and improve their quality of life. Therefore, plasma donors are lifesavers, saving millions of lives around the world each year.
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