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BSI launches new immunodeficiency briefing

The BSI has published a policy briefing on immunodeficiency, a class of disorders that impair the immune system’s ability to mount an appropriate defence. We represent the interests of more than 3,000 immunologists working in academia, clinical medicine, and industry. Many of our members diagnose and treat patients with immunodeficiency conditions, while others work in the lab to identify underlying causes and implications to develop effective diagnostic and treatment options. For this reason, we encourage people to learn about this class of diseases which have moulded a large area of immunological work.

The immune system is the body’s natural defence and is made up of cellular and molecular components that protect us from disease. In immunodeficiency, one or more of these components is impaired and the immune system becomes less equipped for defence. Patients with these conditions are therefore more susceptible and can become very ill from an infection that their healthy counterparts could fight off. That said, immunodeficiency is almost always associated with severe infections that persist, recur and/or lead to complications, making these disorders severely debilitating and even fatal. Patients suspected of having one of these conditions will be referred to a clinical immunologist, where they can be diagnosed and managed. 

There are two types of immunodeficiency disorders: primary immunodeficiencies (PID) and secondary immunodeficiency (SID):

Primary immunodeficiency (PID)

Bubble boy SCID
David Vetter, the 'bubble boy'

​PIDs result from genetic mutations and so are typically present from birth. PIDs are relatively rare but are extremely diverse with over 300 mutations identified to date. Approximately 6 million people in the world and 5,000 people in the UK live with a PID. Many of the mutations are linked to the X-chromosome, so up to 70% of PIDs occur in men (males only have one X chromosome compared females who have two X chromosomes).

PIDs are categorised based on the part of the immune system disrupted by the mutation. For example, PIDs associated with a mutation that causes impairment to T cells (a key immune cell type), are categorised as T cell immunodeficiencies. Severe combined immune deficiencies (SCIDs), which are characterised by the disturbed development of T and B cells, are the most severe form of PID.

You may have heard of ‘The Bubble Boy’, a name dubbed by the media to describe one of the most famous patient cases of SCID. David Vetter, a young boy from Texas in the USA, was born in 1971 with SCID, making him extremely vulnerable to viral, bacterial and fungal infectious diseases. At this time, treatment options were limited, so he lived much of his life in a sterile chamber to avoid coming into contact with infections. He received a bone marrow transplantation from a healthy donor, the most common form of treatment for SCID. Sadly, Vetter died at the age of 12 from Burkitt’s lymphoma following Epstein-Barr virus infection, probably transmitted from a bone marrow transplant he received.

Secondary immunodeficiency (SID)

SIDs typically develop later in life as a result of a primary illness, such as chronic infection or other external factors such as malnutrition.

To give an example, one of the most well-known SIDs is acquired immune deficiency syndrome (AIDS), which results following chronic untreated HIV infection. HIV causes impairment to a type of T cell called CD4+ T cells. Without treatment, HIV infection leads to a decline in CD4+ T cell numbers, and the symptoms of AIDS begin to manifest when the T cell count drops below 200 cells per mL of blood. At this point, the patient is extremely vulnerable to contracting life-threatening infections. However, anti-viral therapies, namely Highly Active Antiretroviral Therapy (HAART), taken during HIV infection allow the T cell population to recover and resume normal function. HAART introduction has significantly expanded life expectancy in these patients and makes the onset of AIDS far less likely. That said, treating and avoiding SIDs, requires treating the primary illness or cause.

The importance of supporting immunodeficiency research

The BSI recognises the importance of supporting immunodeficiency research. PIDs are rare but are extremely serious and a PID diagnosis is life-changing for the child and their family. Early diagnosis and effective treatment options are therefore critical for their survival.

Current therapies for several PIDs include bone marrow transplantation and in the case of infection, aggressive use of antibiotics, antifungals and interferon to stimulate immune system function. The most effective treatment for SIDs involves tackling the primary cause, for example malnutrition or chronic infection.

While these treatment methods are effective, they are used to manage the condition rather than cure it and patients remain highly susceptible to infection. There is a lot of research into novel therapies, such as gene therapy, which presents an opportunity to go into a patient’s genetic makeup and fix the faulty gene. Currently, gene therapy is offered for a small number of immunodeficiency conditions, but further research and clinical trials are required so that this option can be offered to more patients across more conditions. Also, the use of gene therapy in conjunction with the new genome-editing technology, CRISPR/Cas9, provides hope for the specific insertion of a healthy gene to replace the mutated gene. This technology is still in the early stages of development and continued research is vital to translate the technology into the clinic for immunodeficiency gene therapy.

Primary and secondary immunodeficiency encompass a very large field of immunology and there is a considerable amount of research going on to understand the origins and treatment of individual diseases. Understanding more about immunodeficiency will also help to further our understanding of the fundamentals of the immune system and will therefore also contribute to medical advancement across several other disease areas.

The BSI supports many immunologists whose work falls across these areas and we encourage people to learn more about these diseases and the research ongoing. 

Shannon Lacombe

Policy & Public Engagement Officer, BSI

You can read the full BSI briefing on immunodeficiencies in the Policy and Public Affairs section of our website.