Incontinentia pigmenti (IP) is characterized by skin inflammation at birth, accompanied by complications that can differentially affect various organs throughout life, including the eyes, teeth, bones, and brain. This condition is caused by a mutation in the NEMO gene (Nuclear Factor Kappa B Essential Modulator), located on the X chromosome. NEMO plays a crucial role in regulating the immune response and cell survival. In female patients, the mutation is present in a heterozygous state, meaning that only one copy of the gene is altered. In contrast, the functional absence of NEMO in male fetuses is lethal.
In 2020, it was demonstrated that 15% of patients severely affected by COVID-19 express autoantibodies against interferons-α, cytokines essential for antiviral immunity. The production of these autoantibodies is often linked to genetic predispositions. An international clinical consortium studied a cohort of 131 female patients with incontinentia pigmenti and unexpectedly found that 36% of them express anti-interferon-α antibodies. Increased susceptibility to COVID-19 was also observed in this population during the pandemic.
Researchers at CEA-IRIG developed a genetically modified mouse model mimicking the disease characteristics. These mice exhibit abnormal thymus, an organ essential for regulating autoimmunity. This anomaly was also observed in some incontinentia pigmenti female patients, as well as in a deceased male fetus carrying the NEMO mutation.
This study revealed an unsuspected vulnerability of incontinentia pigmenti patients to viral infections, highlighting the need for special attention during epidemics. It also demonstrates a new role for the NF-κB pathway in thymus development and function.
Fundings
La fondation Incontinentia pigmenti