What are Primary Immunodeficiencies (PIDs)?
What are Primary Immunodeficiencies?
Learn from IPOPI’s educational video series on PIDs. Scroll down for our videos covering PID Diagnosis and Treatment.
Published November 7, 2022
Primary immunodeficiencies (PIDs, also referred to as ‘Inborn errors of Immunity’ — IEI) are a large and growing group of over 485 different genetic defects caused when some components of the immune system (mainly cells and proteins) are lacking or do not work properly.
Whilst PIDs are generally recognised as rare disorders, some are more common than others and taken as a whole they represent an important group of people whose lives are profoundly impacted by their condition.
The majority of PIDs are caused by genetic defects of the immune system which are hereditary for most of them. The immune system normally helps the body fight off infections caused by germs (or ‘micro-organisms’) such as bacteria, viruses, fungi and protozoa. Because their immune systems do not work properly, people with PIDs are more prone than other people to infections. It also helps in preventing inflammation, autoimmunity, severe allergies and malignancies.
When PIDs are left underdiagnosed or are misdiagnosed, the immune system remains defective, often leading to illness, disability, permanent organ damage or even death.
Diagnosis
Whilst it is estimated that around 60% of PIDs can be easily diagnosed with simple and inexpensive blood tests, many PIDs remain underdiagnosed on a global scale. Hopefully, as the technical ability to identify gene defects improves, more and more genetic causes of PID are being identified.
Medicine and Science are advancing very rapidly and novel therapies that target the specific cause of the disease are becoming available. These may have significant advantages for PID patients and it is important that patients throughout the world have access to these treatment possibilities.
Screening for some of the most severe forms of immunodeficiency, such as Severe Combined Immunodeficiencies (SCID), will also diagnose more individuals at an earlier stage, thus improving treatment outcomes.
Treatment
With appropriate access to the different and very effective therapies which can only happen if the early and correct diagnosis is made, many sequelae will be avoided and the lives of patients will be saved.
People with PIDs are typically treated by doctors who specialise in diseases of the immune system. How a patient is treated depends on which PID they have, and on many other factors. Mainstay or curative treatments for PIDs include immunoglobulin (IG) replacement therapies, Hematopoietic Stem Cell Transplantation (HSCT, also known as ‘bone marrow transplantation’), gene therapy, cytokines such as Granulocyte-colony stimulating factor (G-CSF), recombinant gamma interferon, enzyme replacement therapy such as recombinant adenosine deaminase for patients with ADA1 deficiency, anti-infectious prophylaxis (with antibiotics, antifungals and/or antivirals), monoclonal antibodies, among others.
Immunoglobulin replacement therapy
In the case of IG replacement therapies, it is important to know that different IG products are not interchangeable or mixable. IG can be administered intravenously or subcutaneously. They are considered essential medicines for PIDs by the World Health Organisation. Intravenous immunoglobulin (IVIG) infusion usually takes 2-4 hours allowing high doses to be given and only needs to be given every 3-4 weeks which may suit some patients better.
Subcutaneous immunoglobulin (SCIG) can only be given in small doses. It only takes 1-2 hours and can often be given at home by patients themselves, parents or carers. This option may therefore be more convenient for some patients. SC infusion preceded by an SC infusion of recombinant human hyaluronidase, which is known as ‘facilitated’ subcutaneous immunoglobulin (fSCIG) allows patients to have SC infusions every 3-4 weeks. IG therapy should be discussed on a shared-decision basis for each individualised case, according to patient needs and preferences.
PID Classification
PIDs are currently classified by the IUIS PID/IEI expert committee into 10 groups: predominantly antibody deficiencies; combined immunodeficiencies; combined immunodeficiencies with associated or syndromic features; diseases of immune regulation; congenital defects of phagocyte number or function, or both; defects of innate immunity; auto-inflammatory disorders; complement deficiencies, based on the main immunological defects; phenocopies of Primary Immunodeficiencies and inherited bone marrow failures.
For more information
For more details on the classification of PID read our leaflet ‘How are primary immunodeficiencies classified?’
We are committed to continuing to disseminate information to patients, their relatives and doctors and work towards better access to early diagnosis and treatment for all patients living with a PID.
For more information about PIDs and how they are treated, diagnosed and advice on how to stay healthy please refer to the IPOPI PID information leaflets.
