What is PID
Frequently Asked Questions
📌 Members Information:
Here we answer patients’ questions on aspects of the different treatments available for PIDs.
Answers to your questions about Primary Immunodeficiencies from the UK
FAQs were reviewed by Dr Matthew Buckland, Chairman of our Medical Advisory Panel and Dr Bobby Gaspar, Professor of Paediatrics and Immunology, Great Ormond Street Hospital, London. August 2014.
Immunoglobulin therapy
Q. I have been on 3-weekly immunoglobulin infusions for a long-time. Will this make my veins brittle?
A. Veins can usually recover in the 3-week gap. If your veins do become brittle then your immunology team might recommend changing to another way of giving immunoglobulin such as subcutaneous infusion.
Q. Does immunoglobulin therapy help prevent dementia?
A. There are a number of studies that have looked at IVIG in Alzheimer Disease and there is no evidence of benefit. There are some rarer infections of the central nervous system, associated with loss of higher or cognitive function and good immunoglobulin treatment prevents these infections from taking hold.
Bone marrow transplantation (BMT)
Q. How often can you do a bone marrow transplant (BMT) for a PID?
A. Yes sometimes a BMT doesn’t work because the graft fails and then it may be possible to consider doing another transplant. However this is dependent on finding another suitable donor and the medical condition of the patient considered for subsequent transplant. There can also be a build-up of toxicity in the body from the chemicals used to prepare the body for transplant during chemotherapy that can complicate further attempts at BMT. Second transplants have been done successfully for a number of PID patients but as mentioned above, a number of different factors need to be taken into account.
Q. Is a bone marrow transplant an option for people with CVID?
A. This depends on the type of the CVID, its genetic basis and also the health problems, past and present that the person may have. We know, at present, that 10 different genes can cause CVID and this is allowing doctors to subgroup CVID patients into those for whom BMT may or may not be a useful treatment option. One group of people with CVID who have mutations in the enzyme PIP kinase 3 have had BMT with good outcomes but overall there is not much historical information on BMT in CVID. In some cases the outcomes, where poor, have to be treated with caution because the BMT was sometimes done on patients who were already ill.
Q. Is BMT only possible for children with PID?
A. No over the past few years more adults have started to be treated by BMT but the numbers are still low. One recent major advance has been the development of what is known as ‘reduced intensity conditioning’; this is a milder form of chemotherapy used to prepare the patient for the donor’s bone marrow. This has been used successfully in BMT for some adults with PID. It is likely that more adults with PID will be treated by BMT in the next few years.
Q. Why is BMT for adults more difficult than that for a child?
A. Usually adults who are being considered for BMT have lots of chronic problems such as lung and gut disease. These chronic problems and chronic infections often make BMT more difficult. Also because of the risks of BMT, the choices of whether a BMT is the right thing to do is more difficult especially since adult PID patients will have jobs, children, etc.
Q. Can parents be a bone marrow match and so a donor for their child?
A. BMT works best when there is a 10/10 or 9/10 match of important markers on cells between the donor and the person having the BMT. A parent may only be a 5/10 or 6/10 match so they not ideal as donors. However, a brother or sister may have a 25% chance of being a match and are often used as donors.
Q. What happens if a BMT match cannot be found within the family?
A. Once doctors have exhausted the possibility of finding a related donor within the family then they will begin the search of a match on national registries such as the Anthony Nolan Registry and cord stem cell banks. Searches can also be made worldwide through international registries. Umbilical cord blood is increasingly being used and this widens the options available.
Gene therapy
Q. My child has had gene therapy to correct his PID. Does this mean his PID won’t be passed on to his children?
A. No, gene therapy only corrects the defect in the cells of the bone marrow of the person and not the reproductive cells such as sperm that will still carry the faulty gene causing the PID. For example a boy who had received gene therapy for an X-linked disorder will have daughters who will carry the condition but will not have affected sons. It is important to consider family planning issues at the appropriate time and your health team will help with this.
Q. How many people have had gene therapy to treat their PID?
A. Over 100 people have had gene therapy for PID. The work is taking place all over the world with groups working together sharing gene therapy tools and methods. There are currently collaborative trials and the major PIDs being targeted are X-SCID, ADA-SCID, WAS, X-CGD, XLP1 and XLA.
Q. Why do some children who have had gene therapy to treat their SCID still need immunoglobulin therapy?
A. In some cases not all the immune cells are completely corrected by gene therapy. If B cells are not fully corrected (the cells that make immunoglobulin) then the individual may have to continue on immunoglobulin therapy.
Q. Why is gene therapy being developed for some PIDs and not others?
A. Developing gene therapy depends on an in-depth understanding of the genes causing the PID. For example knowledge is needed on the precise genetic fault (mutation), where it is in the DNA make-up of a cell, what controls the gene involved and in what cells the protein product of the gene is expressed. Unfortunately, for some PIDs this information is not known at present.
Use of steroids
Q. I’ve been on long-term steroids and worried about osteoporosis, weight gain and cholesterol levels?
A. Doctors when they prescribe steroids carefully weigh up the benefits versus health risks. They will carefully monitor your health and tailor the doses given and will keep them at the lowest level needed to give clinical benefit. Calcium and vitamin D supplements may be recommended to help prevent bone thinning (osteoporosis).
Answers to your questions about Primary Immunodeficiencies South Africa – now referred to as Inborn Errors of Immunity (IEIs)
FAQs were reviewed by Prof Monika Esser, Chairman of our Medical Advisory Panel and Prof Jonny Peter and Prof Andre van Niekerk March 2023
Q: If you or your child were diagnosed with PID/IEI what would be the first questions you would ask?
A: Why did I get this? Can it be cured/treated? What treatment is available? What is the expected quality of life with this condition? What is the life expectancy? Could it have been prevented?
Q: Can Primary Immune Deficiency/IEI be cured?
A: Certain forms of Severe Combined Immune Deficiency (SCID) and an increasing number of IEIs, e.g. Chronic Granulomatous Disease can be cured by a successful stem cell transplant (e.g. bone marrow, cord blood, peripheral harvested stem cells). Therefore early diagnosis is important before irreversible organ damage has occurred. Gene therapy holds great promise for curing PID’s, but later onset of cancers is still a problem. The more common antibody deficiencies are usually treatable with Immunoglobulin replacement infusions assisted by antibiotics and vaccinations.
Q: How safe is the local immunoglobulin therapy in terms of transfer of infections e.g. Hepatitis and AIDS?
A: Locally available Immunoglobulin (Ig) is as safe as any overseas product because the safety and quality controls, including nucleic acid amplification (NAT) testing for Hepatitis C and HIV are as strict as those for overseas products. In South Africa plasma is sourced from the blood donations of healthy unpaid volunteers. However it is a blood derived product and very rarely virus contamination (not HIV) has occurred overseas. Therefore the product, like any other transfusion should only
be used for the correct medical indications and judiciously to be available for PID patients who depend on a regular supply.
Q: How safe is the long-term use of immunoglobulin therapy?
A: The safety profile of long-term Immunoglobulin therapy has been well established. All blood derived products are registered with the Medicines Control Council of South Africa in terms of their safety, efficacy and quality. There has been no documentation of residual effects with long-term use of intravenous immunoglobulins. Follow up of patients who have been on regular IVIG for decades now shows improved quality of life and equivalent ability to work compared to a person without PID. But treatment should be supervised by a doctor who regularly sees the patient holistically. Too little Ig treatment and excessively long intervals between treatment (generally more than three weeks in the case of intravenous Ig) can also result in recurrent infections and the outcome can be almost as bad as without treatment. This is not a complication of the treatment but of incorrect treatment and it is avoided by regular serum trough levels of IgG and medical check ups. As Ig transfusions do not prevent all infections, the IEI patient may also need to be antibiotics in addition, or require additional nutrition.
Q: Primary Immune Deficiency is a chronic condition. Has the state established the infrastructure for home therapy e.g. home nurses, like in other countries?
A: There is currently only assistance or plan for home therapy with certain Medical Aids. A universal access to home therapy would need extensive training and resources.
Q: Could the medical fraternity advise a standard procedure in terms of clinical management of anyone with PID, obviously tailored to the need of the individual? Could this be made available on the website or in the brochure going to the doctors?
A: Yes. Standard guidelines for diagnosis and investigations are available e.g. JMF guidelines – and the IDF (see useful websites). Treatment is often very individual, other than the standard guidelines for Immunoglobulin replacement. Specific medical protocols for individual diagnoses are available. In 2022 extensive recommendations for the indications and use of Immune replacement therapy for patients in South Africa have been agreed on by practitioners in the field in South Africa and published on the ALLSA website.
Q: Is it safe for patients with Primary Immunodeficiency to receive the seasonal flu vaccine?
A: The flu vaccine, now in stock in many pharmacies (although some stocks are already said to be running low) and to be made available in government clinics from April, is not “live” and therefore safe for PID patients who do not have severe T-cell deficiencies. Although it could be useful for PID patients’ immunity to the flu virus, it is advisable to consult the patient’s physician before having the vaccine. Before receiving the vaccine, the PID patient should also be in good health. If younger than two and a half, two vaccines will be required, four weeks apart. Preventative measures like hand washing should nonetheless continue throughout the flu season.
Q: Is it necessary that the Polygam goes at 100ml per hour or can one speed up the by perhaps 150ml per hour and then 200ml per hour after a patient received Polygam for more than say 2 years?
A: In practice experience is that the overall Infusion speed after the first 15 to 30 minutes (30 to 60 ml/ hour in adults and 0.01-0.02ml/ kg/minute in children) after the first three infusions can be advanced carefully, but if any side effects especially flushing or rash occur – step back immediately to previously tolerated dose. Depending on the individual patient and the diagnosis we have witnessed some very ‘non standard’ infusion speeds! If the patient has own IgG antibodies – like most Common Variable or Hypogammas do, we would not push the limits past any slight discomfort and not go past 150ml /hour infusion (120-150ml/hour) speed, (and children 0.08ml/kg/min) especially with home infusions. Use a 20 drop/ml infusion set. Also some patients are premedicated with Phenergan (antiallergy) and or steroids (Solucortef) and in this context one would also be careful – slower infusions may then not need these medications. Special caution for patients with kidney problems is advised. All patients must be well pre-hydrated – this may help prevent a number of the above side effects.
Q: Bearing in mind patient confidentiality, is there a national registry of patients with PID (as they have in other countries) and if not, would the medical profession like one developed?
A: A national registry with support from the industry has been established in 2006 and is stored on a secure server at Tygerberg Hospital, University of Stellenbosch. Only patient data with full patient/parent consent are stored (registered study with ethics number) and all data is strictly confidential. Information exchange of registry results with other countries and continents enables us to see different genetic patterns of diseases and incidences. It may be possible in future to assess the outcome on specific PIDs with good record keeping. This will result in better patient care, while serving to increase awareness for these rarer conditions.
Q: Is genetic diagnostic available in South Africa?
A: Yes. Please consult your physician/paediatrician for guidance on this in consultation with a genetic counsellor