Definition
Type I interferonopathies” are a group of diseases in which the immune system produces abnormally high levels of type I interferons. Interferons are natural proteins produced by the body to fight infections, such as viruses.
They play an important role in activating the immune system. However, in type I interferonopathies, this excessive production of interferons can become harmful. It leads to chronic inflammation, which can damage tissues and organs.
Genetics
Type I interferonopathies are associated with mutations in genes affecting the interferon pathway. These mutations disrupt the normal functioning of immune cells, leading to overproduction of interferons. These mutations are mostly hereditary (transmitted by parents) and rarely spontaneous (sporadic, with no family history).
There are over 20 known genes.
The most common diseases are: Aicardi-Goutières syndrome (AGS), SAVI syndrome, COPA syndrome, proteasome abnormalities (PRAAS), spondyloenchondrodysplasia (SPENCD).
Clinical
Symptoms vary from person to person and depend on the specific type of type I interferonopathy.
They include:
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General manifestations such as recurrent fevers (with no obvious cause of infection) or fatigue.
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Skin rashes such as purplish patches on the extremities, mottling, ulcers, redness of the cheeks or skin.
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Neurological manifestations such as gait disorders, headaches, convulsions, developmental delay, meningitis, brain atrophy, etc.
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Articular or muscular manifestations with pain and contractures
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Lung problems: such as difficulty breathing due to inflammation of the lungs (pneumopathy or fibrosis).
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Enlarged liver or spleen, reduced white blood cell count
Some interferonopathies, such as Aicardi-Goutières syndrome, mainly affect children, while others can appear at any age.
Diagnostic
The disease is suspected after :
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a thorough clinical examination and history-taking, including personal and family history.
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a blood test to check liver and kidney function, as well as figurative blood elements (red, white and platelet cells), and look for inflammation (C-reactive protein, serum amyloid A protein or SAA).
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to study the interferon pathway, we perform an interferon signature during a simple blood test.
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certain imaging tests, such as brain, thoracic and abdomino-pelvic CT scans, and MRI to evaluate the organs affected.
Confirmation is always provided by genetic analysis via a blood test to identify the mutations responsible for the disease => Early diagnosis is essential for better disease management.
Evolution
These are serious diseases that often resist conventional treatments.
Treatment is ideally targeted at the affected interferon pathway.
Regular clinical and biological monitoring at an expert center is essential.
Treatment
There is no cure for type I interferonopathy, but several treatments are available to reduce symptoms and limit complications:
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JAK inhibitors (anti JAK) are used to block the activated JAK pathway in type I interferonopathies. Several molecules are marketed in tablet form.
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A drug that inhibits the interferon receptor, called IFNAR, has been developed: anifrolumab.
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Clinical trials are underway with reverse transcriptase inhibitors for Aicardi Goutières syndrome.
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In very severe forms, allogeneic bone marrow transplantation may be proposed.
Certain anti-inflammatory drugs may be offered to relieve pain.
Supportive care includes physiotherapy, nutritional advice and psychological support to improve quality of life.
Treatments are tailored to each patient, depending on symptoms and disease severity.
Although interferonopathies are rare and complex diseases, early diagnosis and appropriate treatment in an expert center accustomed to dealing with them is advisable.