Why immunoglobulin treatment

In primary or secondary hypogammaglobulinemia low IgG , Ig replacement therapy protects against infections by providing an adequate amount of IgG in the blood 3. Human immunoglobulin plays an important role in the treatment of many diseases, including diseases for which there is no other alternative treatment 3,4. Currently, more than inflammatory and autoimmune disorders are also treated with IVIG. SCIG can be given in two ways: conventional or facilitated.

The facilitated method uses an additional enzyme medication to increase the amount of Ig that can be delivered during each subcutaneous infusion.

The individual with PI or caregiver and the prescriber should have a discussion about which route of administration is most appropriate. There are advantages and disadvantages for each route of administration Table IVIG has allowed infusion of higher doses over a short time and historically has been the standard route of administration. It must be administered by a healthcare professional. This therapy does not require venous access and is associated with the slow release of Ig from the subcutaneous tissues into the blood, which enables IgG levels to remain consistent and steadier between infusions 6.

Currently, among those receiving Ig replacement therapy in the U. The individual with PI or caregiver and the prescriber need to make a decision on the route of therapy that is best for the individual person. All options are clinically effective. There are more than 25 different Ig preparations available worldwide.

The preparations vary in a number of ways, including the distribution of IgG subclasses, stabilizers, and infusion details. All Ig products are made from human source plasma. Source plasma is different than recovered plasma, which is collected through whole blood donation where plasma is separated from its cellular components. This source plasma is pooled from thousands of plasma donations by a process called plasmapheresis in which the liquid part plasma is separated from the red and white cells.

The red and white cells are then returned to the patient. This allows a specific donor to return to the plasmapheresis center monthly. Usually a pool or lot of Ig product is derived from approximately 10, donors. This ensures that a pool or lot of Ig contains a broad spectrum of specific antibodies that are found in the general population which then provide protection to people with PI.

All Ig products licensed in the U. There are multiple safety steps in the production of Ig: donor screening, viral removal, and inactivation of viruses. All plasma donors undergo a very rigorous screening process that includes a detailed history of infections and risk behaviors, and testing of their plasma for certain viruses using very sensitive techniques.

Donors 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 excluded from donation if risk factors are identified.

Plasma centers can look at the donation history for each donor. The FDA also requires blood 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 is discarded.

After donation, the individually donated plasma is tested for infectious agents before being pooled with plasma from other donors. The pooled plasma is then divided up and different methods of fractionation and filtration help to separate out the IgG molecules.

At multiple times throughout this process, the pool is tested for viral safety before additional safety measures are implemented. This prompted the addition of an extra viral inactivation step in the manufacturing process. Now multiple safety measures, including pasteurization, low pH, low pH with pepsin, and solvent detergent help dissolve the lipid enveloped viruses, including hepatitis C. An additional safety step is chromatography, a technique widely used to obtain pure ingredients from mixtures.

More recently, a final ultrafiltration or depth filtration step has been added to remove the possibility of transmission of prion related diseases mad cow disease. Transmission of HIV, which is destroyed in the first ethanol fractionation step in the production of Ig, has never been documented with the use of any Ig replacement therapy. Many factors, however, are considered when the medication is prescribed.

Doses are adjusted for clinical efficacy, with the expectation of minimizing the frequency and severity of recurrent infections while minimizing side effects of the medication. IgG levels are usually monitored over time and correlated with the response to therapy. With SCIG, there is a steady level of IgG present in the bloodstream due to the more frequent dosing regimens Figure and slower rate of absorption.

The goal is to keep the levels of Ig in the blood stream above a certain level even when the level is at its lowest the trough level right before the next infusion is due. Uses: IVIG is given through a vein. Most immunologists strongly discourage the use of central catheters to administer IVIG due to the increased risk of serious blood infections and the development of blood clots. Placing a central venous catheter, also known as a port, due to poor venous access increases the risk of infections and blood clots, and it should be strongly discouraged.

Given the very serious risk involved with the use of implantable ports, individuals should instead consider switching to the subcutaneous route of administration SCIG if there is a vein access problem.

IVIG is typically given every three-four weeks at a dose determined by the prescriber. Infusions can be given in various settings including an inpatient or outpatient infusion suite, physician office, or in the home. IVIG is administered by a healthcare professional, and the procedure is scheduled in advance. In special extenuating circumstances, individuals can be instructed to self-infuse this therapy after they are stable on the treatment as long as IV access can be established.

The medical professional should, however, stay with the individual for the length of the infusion because of the risk of serious side effects, such as anaphylaxis. Individuals may be at increased risk for developing an adverse reaction if they have never received IVIG, have active infections or pre-existing conditions such as pneumonia or bronchiectasis , or are switching products.

Individuals with a history of migraine headache may be at risk for a postinfusion headache reaction. The prescriber of the therapy can modify IVIG dosing by decreasing the rate of infusion or adding other medications to the prescription.

Medications such as acetaminophen, diphenhydramine, non-steroidal anti-inflammatory drugs, or corticosteroids can help prevent side effects during and after an infusion. It is important to know, however, that repeated use of corticosteroids used to manage IVIG side effects may lead to longterm problems associated with repeated steroid use.

Frequency and duration of infusions depend on the underlying disease and the clinical course. IVIG can take several weeks to fully take effect.

The dosing of IVIG also varies dependent on the condition being treated, but usually is based on body weight. The majority of people do well with IVIG, experiencing only minor side effects. IVIG may cause infusion reactions, including fevers, chills, flushing, rash, muscle aches, and nausea. Headaches are also relatively common.

These are generally not severe and improve with analgesics and antihistamines. Rarely, IVIG may cause aseptic meningitis inflammation of the lining of the brain without an infection. Owing to this theoretical risk, British plasma is not used for making immunoglobulin. The other risk is new infections that start to affect humans, either because of global climate change or change in behaviour e.

One example of this is a virus that affected people in New York and entered the blood supply there. It is very difficult to predict whether new infections, which could be spread by immunoglobulin, will appear in the future. However, the immunoglobulin manufacturers and immunologists around the world are constantly on the lookout for any problems such as this. The first step the manufacturers take is to get to know the plasma donors really well.

Manufacturers insist that their donors donate regularly. Each time a donor attends the blood centre they are asked a lot of questions, on topics ranging from their sex lives to any recent travel. The plasma is not released for processing until the blood tests have come back negative. The second step is that the plasma is treated in a few different ways to get rid of infection. Depending on the manufacturer, the plasma will get a combination of heat treatment pasteurisation , addition of solvent detergent, and nano-filtration with or without ultraviolet light treatment.

Donor centres and immunoglobulin manufacturers have very high standards for minimising the risk of infection getting into the immunoglobulin supply. Donor centres and manufacturers are inspected regularly and will be closed down if there is any hint of a problem. A final important safety step is carried out by immunologists, who either do annual hepatitis checks or save a sample of blood for infection testing. Your child will also be kept on the same immunoglobulin product once they have started, provided that it is well tolerated.

It is through this kind of surveillance that we can be confident that immunoglobulin and its administration is as safe as possible. You can expect to see the immunology team at least two or three times a year. Sometimes follow-up will be done by a specialist trainee doctor if it is a recognised teaching centre.

Are there any problems? Has anything else changed? At monitoring visits, a huge amount of information will be swapped between you and the immunology team. A lot of people jot down any questions they think of in the days leading up to the appointment. You might want to take someone along to the appointment to remember what has been said, or you might just want to take notes.

Immunoglobulin is manufactured in batches. Several thousand donations of plasma are pooled in each batch. Very occasionally there are problems with some batches. For example, recently one batch of immunoglobulin caused some people to get an itchy rash. As it was possible to identify which batch was causing the rash, replacement immunoglobulin could be sent out quickly. The tests your child had before starting immunoglobulin were designed to check whether they would need immunoglobulin for life.

However, sometimes immunoglobulin is recommended for people whose immune deficiency may be only temporary. This can happen in babies and small children or when the immune system has been damaged by medications.

If your child does stop immunoglobulin, the immunology team will monitor them closely. However, each manufacturer must follow international standards on product safety.

The blood donor centres and manufacturing plants of all the different companies are inspected from time to time. If they are on weekly SCIG, the schedule could be adapted to allow a break for up to two weeks, or sometimes a single dose of IVIG can be given immediately before the holiday. You will not be allowed to give immunoglobulin at home until you are confident about doing so.

You might have to do a short exam! Intravenous immunoglobulin, or IVIg, is a treatment that combines immunoglobulins im-yoo-no-glob-yoo-lins donated by different people to treat various conditions. Intravenous means that it is given by a drip. IVIg and other immunoglobulins are made from plasma. You can find out more about donating plasma on the NHS Give blood site. IVIg is used to reduce the effects of some inflammatory conditions that involve the immune system, also known as autoimmune diseases.

It may be used in the treatment of several different conditions, including:. IVIg should start to work within a few weeks, but this will vary depending on which condition you have and how you respond to the treatment.

If IVIg works for you, the effects can last for a few months. Before you start IVIg, your doctor will check the levels of immunoglobulins in your blood. You might not be given IVIg if you've had a previous reaction to immunoglobulin, and you may not be able to have some types of IVIg if you have an intolerance to fruit sugar. IVIg is given through a drip into a vein, this is known as intravenous infusion. The infusion will take several hours as the drug has to be given slowly.