Definition
Type I interferonopathies are a group of rare innate immune disorders in which the immune system produces an abnormally high amount of type I interferons.
Interferons are natural proteins made by our bodies to fight infections, such as viruses. They play an important role in activating the immune system.
However, in type I interferonopathies, this constant production of interferons can become harmful. It causes chronic inflammation, which can damage tissues and organs.
Genetics
Type I interferonopathies are associated with gene mutations affecting the interferon pathway. These mutations disrupt the normal function of immune cells, leading to overproduction of interferons.
These mutations are mostly inherited (passed down from parents) and rarely occur spontaneously (sporadically, without family history).
More than 30 genes are known to be involved.
The most common diseases include: Aicardi-Goutières syndrome (AGS), SAVI syndrome, COPA syndrome, and more rarely proteasome-associated autoinflammatory syndromes (PRAAS), and spondyloenchondrodysplasia (SPENCD).
Clinical
Symptoms depend on the specific type of type I interferonopathy and vary from person to person.
They include:
-
General symptoms such as recurrent fevers (without obvious infection), fatigue, or short stature
-
Skin rashes such as purplish patches on extremities, mottling, ulcers on fingers or toes (“chilblains”), and sometimes on the nose and/or ears, redness on the cheeks or skin
-
Neurological symptoms including walking difficulties, headaches, seizures, developmental delay, meningitis, brain atrophy
-
Joint or muscle symptoms such as pain, contractures
-
Lung problems: such as difficulty breathing due to lung inflammation (pneumonitis or fibrosis)
-
Enlarged liver or spleen, low white blood cell count
-
Rarer issues, such as ocular hypertension (glaucoma)
Some interferonopathies, like Aicardi-Goutières syndrome, mainly affect children, while others can appear at any age.
Diagnostic
The disease is suspected after:
A thorough clinical examination and a medical history including personal and family background
Blood tests to check liver and kidney function, blood cell counts (red, white, and platelets), and inflammation markers (C-reactive protein, serum amyloid A or SAA)
To study the interferon pathway, an “interferon signature” test is performed via a simple blood draw
Imaging tests such as brain, chest, and abdominal CT scans; MRI to assess affected organs
Confirmation is always made through genetic testing via a blood sample to identify the mutations responsible for the disease.
=> Early diagnosis is essential for better disease management. It also allows for genetic counseling to identify other potentially affected family members and to provide advice in case of pregnancy planning.
Evolution
These are serious diseases that often resist conventional treatments. Ideally, treatment targets the affected interferon pathway.
Regular clinical and biological follow-up in a specialized center is recommended.
Treatment
There is no curative treatment for type I interferonopathies; a national diagnostic and care protocol is available on the website of the French National Health Authority (HAS).
Several treatments are available to reduce symptoms and limit complications:
-
JAK inhibitors (anti-JAK) are used to block the JAK pathway activated in type I interferonopathies. Several drugs are available in tablet form.
-
A drug that blocks the interferon receptor, called IFNAR, has been developed: anifrolumab, administered via monthly infusion in a day hospital.
-
In very severe cases, a bone marrow transplant may be considered.
-
Some anti-inflammatory drugs may be used to relieve pain.
-
Supportive care includes physical therapy, nutritional advice, or psychological support to improve quality of life.
Treatments are tailored to each patient based on symptoms and disease severity.
As rare and complex diseases, type I interferonopathies require early diagnosis and specialized care in expert centers familiar with their management.