XLA Research Revealed

Current treatments for XLA are not enough

Ben Shillitoe - Consultant in Paediatric Infectious Diseases and Immunology:

"I am pleased to share our latest research highlighting the significant impact of respiratory health on the Quality of Life (QoL) for patients with X-linked Agammaglobulinemia (XLA).

Our findings, alongside our group's previous work, underscore a sobering reality: complications like chronic lung disease are not always fully manageable with current therapies. This research serves as a call to action for the development of new therapeutic strategies to better support the XLA community.

A huge thank you to my collaborators across the UK, the Bubble Foundation, and the Jeffrey Modell Foundation for their vital support in bringing this work to fruition."

XLA - (X-linked agammaglobulinaemia)
IgRT - (Immunoglobulin replacement therapy)

XLA is a rare genetic condition. It means the body cannot make antibodies. Antibodies are proteins in your blood that help fight infections. Without them, people with XLA get ill more easily and more often.

The main treatment for many decades is called immunoglobulin replacement therapy (IgRT). This means giving patients antibodies that have been collected from healthy donors. It helps them fight infections and it saves lives.

But it is not a cure.

What our research found

While IgRT is lifesaving, our research highlights a sobering reality: it is not a cure. Even with the best current medical efforts, many patients continue to suffer from significant, life-altering health complications. Thanks to funding from the Bubble Foundation, researchers in the UK and Hong Kong looked closely at how well this treatment is working.

We found some serious problems.

Lung damage still happens

Even when patients receive regular antibody treatment, many still develop a condition called bronchiectasis.

Bronchiectasis means permanent damage and scarring in the lungs. This makes it harder to breathe and leads to repeated chest infections. Once the lungs are damaged, they cannot fully heal.

Quality of life

For patients with lung damage, everyday life can become very difficult.

In fact, their quality of life can be as low as, and sometimes worse than, people living with Cystic fibrosis.

However, patients with XLA who do not develop lung damage can live lives similar to the general population. This shows how serious bronchiectasis is.

Other health risks remain

Even with regular antibody infusions, patients are still at risk of:

• Long-term sinus infections

• Inflammatory conditions

• Certain types of cancer

The treatment helps, but the "shield" provided by current therapy is simply not complete.

What needs to change

The fact that chronic lung disease still occurs despite our best current efforts proves that we need a revolution in how we identify and treat XLA.

Earlier diagnosis: This may be possible via newborn screening. Further work is urgently needed to determine the feasibility of this screening and to prove that early intervention can fundamentally improve the lives of patients with XLA.

Advances in therapies: We need treatments that do more than just "replace" antibodies. We need "better" therapies, such as gene therapy or more targeted immune modulators that can more closely mimic a healthy immune system and stop complications before they ever start.

What's next?

This research has been instrumental in uncovering these gaps in care. However, it is also a call to action. Further research is not just "desirable". It is sorely needed.

Needed to ensure that a diagnosis of XLA no longer means a lifetime of managing chronic lung damage. Our aim must be to ensure that every child born with XLA has the chance to live a life entirely free from the shadow of chronic disease.

You can find more details on this paper below:
https://rupress.org/jhi/article/2/3/e20250198/281512/Quality-of-life-of-X-linked-agammaglobulinemia